METHODS FOR IDENTIFYING IMMUNOGLOBULIN ASSOCIATED WITH ADVERSE REACTIONS

Description

[0001] The present invention relates to methods for identifying and reducing Fc epsilon I receptor (FcεRI) immunoglobulins (Ig) associated with adverse reactions from plasma or a fraction thereof, formulations and uses of the reduced anti-FcεRI Ig plasma protein product. BACKGROUND

[0002] Immunoglobulins (Ig) are one of the most abundant proteins in plasma and are responsible for complement activation, opsonization, and toxin neutralization. Plasma-derived Ig has become an important plasma product, and global demand is increasing. Human Ig products, both hyperimmune (or “specific”) and normal (or “non-specific”), consist predominantly of IgG. Purified IgG from human plasma is used for prophylactic prevention of infections in immunocompromised patients, replacement therapy for antibody deficiencies in patients, and treatment of conditions related to immunodeficiency, inflammatory and autoimmune diseases, and acute infections in patients. A list of FDA-approved Igs is provided at http: / / www.fda.gov / vaccines-blood-biologics / approved-blood-products / immune-globulins.

[0003] Currently, several commercial intravenous IG (IVIG) products (typically stabilized 5% or 10% (w / v) solutions) are available, including Privigen® (CSL Behring), Flebogamma® (Grifols), Gamunex®-C (Grifols), Gammagard® (Takeda), and Octagam® (Octapharma). More recently, subcutaneous IG administration (SCIG) has become available. Commercial SCIG products (typically stabilized 10%, 16.5%, or 20% (w / v) solutions) include Hizentra® (CSL Behring), Gamunex®-C (Grifols), Xembify® (Grifols), Cutaquig® (Octapharma), and Cuvitru® (Takeda). Other IG products are administered via Petition 870250100974, dated 04 / 11 / 2025, p. 7 / 216 2 / 172 intramuscular (IMIG).

[0004] Although immunoglobulin therapy is effective and generally well tolerated, several adverse effects have been reported over the years. Subject to the immunoglobulin product, most of these events, such as rash, flushing, headache, malaise, fever, chills, fatigue, and lethargy, are transient and mild. However, some side effects, such as immediate hypersensitivity reactions (including urticaria and pruritus), thrombosis, arrhythmia, aseptic meningitis, and hemolytic anemia, are serious. These adverse effects, with varying degrees of severity, are associated with specific immunoglobulin preparations and the individual susceptibility of the patient.Although assessing patient risk factors, reducing infusion rates, and alternating between IVIG and SCIG can minimize adverse effects, it is not known which components of plasma and Ig products are causing these adverse reactions, and sometimes the increased frequency of adverse events can result in the withdrawal of Ig products from distribution. In fact, an excessive number of hypersensitivity reactions involving specific Ig batches occur episodically and unpredictably, leading to the recall of product batches and the quarantine of manufacturing intermediates that may negatively affect the supply of Ig (Product Safety Update; International blood / plasma news, p100, February 2023).

[0005] Therefore, it is evident to those skilled in the art that there is a need in the field for methods to identify and reduce plasma components that cause adverse reactions in individuals from plasma samples or fractions. SUMMARY

[0006] The present invention is based on the inventors' identification of an immunoglobulin (Ig) associated with adverse reactions in individuals. In particular, through statistical analysis of plasma donations, the inventors identified a single plasma donor associated with adverse reactions. Petition 870250100974, dated 04 / 11 / 2025, page 8 / 216 3 / 172 hypersensitivity. Subsequently, the inventors discovered that the plasma from this donor was capable of inducing mast cell and basophil degranulation through activation of the Fc epsilon I receptor-mediated pathway (FcεRI). The inventors further identified that the activation of the FcεRI-mediated pathway was driven by immunoglobulin (Ig) G. Surprisingly, purified IgG products derived from the plasma of a donor associated with hypersensitivity reactions did not clearly induce mast cell or basophil degranulation in vitro through activation of the FcεRI-mediated pathway. It was only with the identification of the individual plasma donor associated with the hypersensitivity reactions that the inventors were able to determine why the purified IgG products were causing adverse reactions in individuals.

[0007] Thus, the inventors' discoveries provide the basis for a method of identifying Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof. The present invention also offers a method for detecting Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof. The present invention also offers a method for screening a plasma sample or a fraction thereof for Fc epsilon I receptor immunoglobulin (Ig) (FcεRI).

[0008] The present invention offers a method comprising contacting a plasma sample or a fraction thereof with a reagent that binds to an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof and detecting the binding of the reagent.

[0009] In one example, the reagent binds directly to anti-FcεRI Ig in the plasma sample or a fraction thereof.

[0010] In one example, the reagent binds indirectly to anti-FcεRI Ig in the plasma sample or a fraction thereof.

[0011] In one example, the reagent is a ligand comprising the Petition 870250100974, dated 04 / 11 / 2025, p. 9 / 216 4 / 172 FcεRI or a fragment or epitope thereof. For example, the FcεRI fragment comprises an α chain of FcεRI. In one example, the FcεRI fragment is a functional fragment. For example, the functional FcεRI fragment is a fragment of FcεRI that, when bound to anti-FcεRI Ig, activates an FcεRI-mediated signaling pathway.

[0012] In one example, the method comprises placing a sample of plasma or a fraction thereof in contact with a ligand comprising FcεRI or a fragment or epitope thereof that binds to anti-FcεRI Ig in the plasma sample or fraction thereof. For example, the binding of anti-FcεRI Ig in the plasma sample or fraction thereof to FcεRI or a fragment or epitope thereof results in the formation of a complex. In one example, the method further comprises detecting the complex, wherein the presence of the complex is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0013] The present invention provides a method for detecting Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, the method comprising:

[0014] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0015] (ii) detecting the complex, the presence of which is indicative of the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof.

[0016] The present invention also provides a method for screening a plasma sample or a fraction thereof for an anti-Fc epsilon I receptor immunoglobulin (Ig), the method comprising:

[0017] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0018] (ii) detect the complex, the presence of which is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0019] The present invention also provides a method for identifying a plasma sample or a fraction thereof suitable for Petition 870250100974, dated 04 / 11 / 2025, page 10 / 216 5 / 172 administration to an individual, wherein the method comprises:

[0020] (i) bring the sample into contact with a ligand that binds to the Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0021] (ii) detect the complex, wherein the presence of the complex is indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, wherein the presence of anti-FcεRI Ig in the sample or plasma fraction indicates that the sample or plasma fraction is not suitable for administration to the individual.

[0022] The present invention provides a method for screening a plasma sample or a fraction thereof to determine its suitability for administration to an individual, wherein the method comprises:

[0023] (i) bring the sample into contact with a ligand that binds to an Fc epsilon I receptor anti-Ig (FcεRI) immunoglobulin in the sample to form a complex; and

[0024] (ii) detect the complex, wherein the presence of the complex is indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, wherein the presence of anti-FcεRI Ig in the sample or plasma fraction indicates that the sample or plasma fraction is not suitable for administration to the individual.

[0025] The present invention also provides a method for identifying a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, wherein the method comprises:

[0026] (i) bring the sample into contact with a ligand that binds to the Fc epsilon I antireceptor Ig (FcεRI) in the sample to form a complex; and

[0027] (ii) detect the complex, wherein the presence of the complex is indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, wherein the presence of anti-FcεRI Ig in the sample or plasma fraction indicates that the sample or plasma fraction is not suitable for use in production Petition 870250100974, dated 04 / 11 / 2025, page 11 / 216 6 / 172 of an Ig preparation for administration to an individual.

[0028] The present invention also provides a method for screening a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, wherein the method comprises:

[0029] (i) bring the sample into contact with a ligand that binds to the Fc epsilon I antireceptor Ig (FcεRI) in the sample to form a complex; and

[0030] (ii) detect the complex, wherein the presence of the complex is indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, wherein the presence of anti-FcεRI Ig in the sample or plasma fraction indicates that the sample or plasma fraction is not suitable for use in the production of an Ig preparation for administration to an individual.

[0031] The present invention provides a method for detecting an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, wherein the method comprises:

[0032] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0033] (ii) detect the complex with a detection protein containing a detectable marker, and the presence of the detectable marker indicates the presence of anti-FcεRI Ig in the sample or plasma fraction.

[0034] The present disclosure provides a method for screening a plasma sample or a fraction thereof for an Fc epsilon I antireceptor immunoglobulin (Ig), the method comprising:

[0035] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0036] (ii) detect the complex with a detection protein containing a detectable marker, and the presence of the detectable marker indicates the presence of anti-FcεRI Ig in the sample or plasma fraction. Petition 870250100974, dated 04 / 11 / 2025, p. 12 / 216 7 / 172

[0037] The present invention provides a method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, and the method comprises:

[0038] (i) bring the sample into contact with a ligand that binds to an Fc epsilon I receptor anti-Ig (FcεRI) immunoglobulin in the sample to form a complex; and

[0039] (ii) detect the complex with a detection protein containing a detectable marker, wherein the presence of the detectable marker indicates the presence of anti-FcεRI Ig in the sample or plasma fraction, wherein the presence of anti-FcεRI Ig in the sample or plasma fraction indicates that the sample or plasma fraction is not suitable for administration to the individual.

[0040] The present invention provides a method for screening a plasma sample or a fraction thereof to determine its suitability for administration to an individual, wherein the method comprises:

[0041] (i) bring the sample into contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (FcεRI) in the sample to form a complex; and

[0042] (ii) detect the complex with a detection protein containing a detectable marker, and the presence of the detectable marker indicates the presence of anti-FcεRI Ig in the sample or plasma fraction, and the presence of anti-FcεRI Ig in the sample or plasma fraction indicates that the sample or plasma fraction is not suitable for administration to the individual.

[0043] The present invention provides a method for detecting Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, the method comprising:

[0044] (i) immobilizing a ligand comprising FcεRI or a fragment or epitope thereof on a solid surface;

[0045] (ii) place the sample in contact with the immobilized binder in Petition 870250100974, dated 04 / 11 / 2025, p. 13 / 216 8 / 172 solid surface, in which the immobilized ligand binds to anti-FcεRI Ig in the sample to form a complex;

[0046] (iii) bringing the complex into contact with a detection protein comprising a variable antibody region, wherein the detection protein binds to anti-FcεRI Ig and wherein the detection protein comprises a detectable marker; and

[0047] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0048] The present invention provides a method for detecting Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, the method comprising:

[0049] (i) immobilizing a ligand comprising FcεRI or a fragment or epitope thereof on a solid surface;

[0050] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0051] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig; and

[0052] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0053] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0054] The present disclosure offers a method for screening a plasma sample or a fraction thereof for Fc epsilon I antireceptor immunoglobulin (Ig) (FcεRI), and the method comprises:

[0055] (i) immobilizing a ligand comprising FcεRI or a fragment or epitope thereof on a solid surface; Petition 870250100974, dated 04 / 11 / 2025, p. 14 / 216 9 / 172

[0056] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0057] (iii) bringing the complex into contact with a detection protein comprising a variable antibody region, wherein the detection protein binds to anti-FcεRI Ig and wherein the detection protein comprises a detectable marker; and

[0058] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0059] The present disclosure provides a method for screening a plasma sample or a fraction thereof for Fc epsilon I antireceptor immunoglobulin (Ig), and the method comprises:

[0060] (i) immobilizing a ligand comprising FcεRI or a fragment or epitope thereof on a solid surface;

[0061] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0062] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig; and

[0063] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0064] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0065] The present invention provides a method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, and the method comprises:

[0066] (i) immobilize a ligand comprising FcεRI or fragment or Petition 870250100974, dated 04 / 11 / 2025, p. 15 / 216 10 / 172 epitope of it on a solid surface;

[0067] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0068] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, wherein the detection protein binds to anti-FcεRI Ig and wherein the detection protein comprises a detectable marker; and

[0069] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0070] The present invention provides a method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, and the method comprises:

[0071] (i) immobilizing a ligand comprising FcεRI or a fragment or epitope thereof on a solid surface;

[0072] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0073] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig; and

[0074] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0075] (v) detect the marker, wherein the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable Petition 870250100974, dated 04 / 11 / 2025, page 16 / 216 11 / 172 for administration to the individual.

[0076] The present invention provides a method for screening a plasma sample to determine its suitability for administration to an individual, wherein the method comprises:

[0077] (i) immobilizing a ligand comprising FcεRI or a fragment or epitope thereof on a solid surface;

[0078] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0079] (iii) bringing the complex into contact with a detection protein comprising a variable antibody region, wherein the detection protein binds to anti-FcεRI Ig and wherein the detection protein comprises a detectable marker; and

[0080] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0081] The present invention provides a method for screening a plasma sample to determine its suitability for administration to an individual, and the method comprises:

[0082] (i) immobilizing a ligand comprising FcεRI or a fragment or epitope thereof on a solid surface;

[0083] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0084] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig; and

[0085] (iv) placing the detection protein in contact with an antibody Petition 870250100974, dated 04 / 11 / 2025, p. 17 / 216 12 / 172 that binds to it and contains a detectable marker; and

[0086] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0087] The present invention provides a method for identifying an individual suitable for plasma donation for the production of an immunoglobulin (Ig) preparation; the method comprises:

[0088] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0089] (ii) detect the complex, wherein the presence of the complex is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the individual is not suitable for donating plasma for the production of the Ig preparation.

[0090] The present invention provides a method for screening an individual suitable for plasma donation for the production of an immunoglobulin (Ig) preparation; the method comprises:

[0091] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0092] (ii) detect the complex, wherein the presence of the complex is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the individual is not suitable for donating plasma for the production of the Ig preparation.

[0093] The present invention offers a method of identifying an individual suitable for plasma donation for the production of a Petition 870250100974, dated 04 / 11 / 2025, page 18 / 216 13 / 172 preparation of immunoglobulin (Ig), the method comprising:

[0094] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0095] (ii) detect the complex with a detection protein that includes a detectable marker, wherein the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the individual is not suitable for donating plasma for the production of the Ig preparation.

[0096] The present invention provides a method for screening an individual suitable for plasma donation for the production of an immunoglobulin (Ig) preparation; the method comprises:

[0097] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0098] (ii) detect the complex with a detection protein that includes a detectable marker, and the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the individual is not suitable for plasma donation for the production of the Ig preparation.

[0099] In one example, the ligand comprises FcεRI or a fragment or epitope thereof. For example, the FcεRI fragment comprises an α chain of FcεRI. In another example, the FcεRI fragment is a functional fragment. For example, the functional FcεRI fragment is a fragment of FcεRI that, when bound to anti-FcεRI Ig, activates an FcεRI-mediated signaling pathway.

[0100] In some examples, Ig anti-FcεRI binds to an epitope of FcεRI activates an FcεRI-mediated signaling pathway. Petition 870250100974, dated 04 / 11 / 2025, p. 19 / 216 14 / 172

[0101] In one example, anti-FcεRI Ig binds to an α chain of FcεRI and activates an FcεRI-mediated signaling pathway.

[0102] In one example, anti-FcεRI Ig binds to an FcεRI epitope and activates another immune signaling pathway. For example, anti-FcεRI Ig binds to an FcεRI epitope and activates an IgE-mediated signaling pathway. In another example, anti-FcεRI Ig binds to an FcεRI epitope and activates an IgG-mediated signaling pathway. In one example, anti-FcεRI Ig binds to an FcεRI epitope, an IgE-mediated signaling pathway, and another immune signaling pathway. In one example, anti-FcεRI Ig binds to an FcεRI epitope, an IgG-mediated signaling pathway, and another immune signaling pathway. In some examples, anti-FcεRI Ig binds to an FcεRI epitope and activates an IgE-mediated signaling pathway and an IgG-mediated signaling pathway. In one example, anti-FcεRI Ig binds to an FcεRI epitope and activates an FcεRI-mediated signaling pathway, an IgE-mediated signaling pathway, and an IgG-mediated signaling pathway.In one example, anti-FcεRI Ig binds to an FcεRI epitope and activates both an FcεRI-mediated signaling pathway and an IgE-mediated signaling pathway. In another example, anti-FcεRI Ig binds to an FcεRI epitope and activates both an FcεRI-mediated signaling pathway and an IgG-mediated signaling pathway.

[0103] In one example, the activation of the signaling pathway mediated by FcεRI induces the activation and / or degranulation of basophils and / or mast cells. In another example, activation of the FcεRI-mediated signaling pathway induces basophil activation. In another example, activation of the FcεRI-mediated signaling pathway induces basophil degranulation. In another example, activation of the FcεRI-mediated signaling pathway induces both basophil activation and degranulation. In another example, activation of the FcεRI-mediated signaling pathway induces mast cell activation. In another example, activation of the FcεRI-mediated signaling pathway induces mast cell degranulation. In one example, activation of the FcεRI-mediated signaling pathway... Petition 870250100974, dated 04 / 11 / 2025, page 20 / 216 15 / 172 FcεRI-mediated signaling induces mast cell activation and degranulation. In another example, activation of the FcεRI-mediated signaling pathway induces both basophil and mast cell activation and degranulation.

[0104] The present invention also offers a method for detecting anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or fraction thereof, the method including the detection of basophil and / or mast cell activation and / or degranulation induced by the plasma sample or fraction thereof, wherein basophil and / or mast cell activation and / or degranulation is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0105] The present invention provides a method for screening a plasma sample or a fraction thereof for anti-Fc epsilon I receptor immunoglobulin (Ig), the method comprising detecting basophil and / or mast cell activation and / or degranulation induced by the plasma sample or a fraction thereof, wherein basophil and / or mast cell activation and / or degranulation is indicative of the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof.

[0106] The present invention also provides a method for screening a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprising detecting the activation and / or degranulation of basophils and / or mast cells induced by the plasma sample or fraction thereof, wherein the activation and / or degranulation of basophils and / or mast cells is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the plasma sample or fraction is not suitable for use in the production of the Ig preparation for administration to an individual.

[0107] The present invention further provides a method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, the method comprising detecting the Petition 870250100974, dated 04 / 11 / 2025, page 21 / 216 16 / 172 activation and / or degranulation of basophils and / or mast cells induced by the plasma sample or a fraction thereof, wherein the activation and / or degranulation of basophils and / or mast cells is indicative of the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof indicates that the plasma sample or a fraction thereof is not suitable for administration to the individual.

[0108] The present disclosure also provides a method for identifying a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprising detecting the activation and / or degranulation of basophils and / or mast cells induced by the plasma sample or fraction thereof, wherein the proportion of activation and / or degranulation of basophils and / or mast cells is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the plasma sample or fraction is not suitable for use in the production of the Ig preparation for administration to an individual.

[0109] In one example, anti-FcεRI Ig is an anti-FcεRI IgG and / or a IgE anti-FcεRI. In one example, Ig anti-FcεRI is both IgG anti-FcεRI and IgE anti-FcεRI. In another example, Ig anti-FcεRI is either IgG anti-FcεRI or IgE anti-FcεRI. In yet another example, Ig anti-FcεRI is IgG anti-FcεRI. In yet another example, Ig anti-FcεRI is IgE anti-FcεRI.

[0110] In one example, anti-FcεRI Ig induces a hypersensitivity reaction in an individual.

[0111] In one example, the binder is immobilized on a solid surface.

[0112] In another example, the method also includes immobilization of the ligand. FcεRI on a solid surface.

[0113] In one example, the method also includes contact of the protein complex with the detection protein comprising a variable antibody region, wherein the detection protein binds to anti-FcεRI Ig and wherein the detection protein comprises the detectable marker. Petition 870250100974, dated 04 / 11 / 2025, p. 22 / 216 17 / 172

[0114] In one example, the method also includes contact of the protein complex with the detection protein comprising a variable antibody region, wherein the detection protein binds to anti-FcεRI Ig and contact of the detection protein with an antibody that binds to it and comprises a detectable marker.

[0115] In one example, the detection protein is an anti-IgG and / or an anti-IgE. In one example, the detection protein is both an anti-IgG and an anti-IgE. In one example, the detection protein is either an anti-IgG or an anti-IgE. In another example, the detection protein is an anti-IgG. In yet another example, the detection protein is an anti-IgE.

[0116] In one example, the detectable marker is selected from the group consisting of a radiolabel, an enzyme, a fluorescent marker, a luminescent marker, a bioluminescent marker, a magnetic marker, a prosthetic group, and a contrast agent.

[0117] A qualified person will understand, based on the description in this document, that in the screening and / or identification methods of a plasma sample or fraction suitable for administration and / or for use in the production of an Ig preparation described in this document, the plasma sample or fraction is not suitable for administration or use if anti-FcεRI IgG is present in a detectable quantity. For example, the presence of anti-FcεRI Ig in the plasma sample or fraction thereof in a detectable quantity indicates that the plasma sample or fraction thereof is not suitable for administration to the individual. In another example, the presence of anti-FcεRI Ig in the plasma sample or fraction thereof in a detectable quantity indicates that the plasma sample or fraction thereof is not suitable for use in the production of the Ig preparation for administration to the individual.

[0118] The methods for detecting the presence of anti-FcεRI Ig will be apparent to the specialist and / or described in this document. For example, the presence of a detectable amount of anti-FcεRI Ig is determined Petition 870250100974, dated 04 / 11 / 2025, page 23 / 216 18 / 172 directly by determining the level of anti-FcεRI Ig in the plasma sample or a fraction thereof. In another example, the presence of a detectable amount of anti-FcεRI Ig is determined indirectly by determining the proportion of basophil and / or mast cell activation and / or degranulation induced by the plasma sample or a fraction thereof.

[0119] In one example, the method comprises determining the level of anti-FcεRI Ig in a plasma sample or fraction thereof.

[0120] In one example, the method comprises determining the level of anti-FcεRI IgG in a plasma sample or fraction thereof. For example, the method comprises determining a detectable amount of anti-FcεRI IgG in a plasma sample or fraction thereof. In one example, the detectable amount of anti-FcεRI IgG in a plasma sample or fraction thereof is at least 40 μg / mL. In one example, the detectable amount of anti-FcεRI IgG in a plasma sample or fraction thereof is at least 45 μg / mL. In one example, the detectable amount of anti-FcεRI IgG in a plasma sample or fraction thereof is at least 50 μg / mL. For example, if anti-FcεRI IgG is present in the plasma sample or fraction thereof at a concentration of at least 40 μg / mL (i.e., in a detectable quantity), the plasma sample or fraction thereof is not suitable for administration to an individual or for use in the production of an Ig preparation for administration to an individual.For example, if anti-FcεRI IgG is present in the plasma sample or fraction thereof at a concentration lower than 40 μg / mL (i.e., not in a detectable quantity), the plasma sample or fraction thereof is suitable for administration to the individual or for use in the production of an Ig preparation for administration to the individual.

[0121] In one example, the method comprises determining the level of anti-FcεRI IgE in a plasma sample or fraction thereof. For example, the method comprises determining a detectable amount of anti-FcεRI IgE in a plasma sample or fraction thereof. In one example, the Petition 870250100974, dated 04 / 11 / 2025, page 24 / 216 19 / 172 The detectable amount of anti-FcεRI IgE in the plasma sample or fraction thereof is at least 0.1 kU / L. In one example, the detectable amount of anti-FcεRI IgE in the plasma sample or fraction thereof is at least 0.5 kU / L. In another example, the detectable amount of anti-FcεRI IgE in the plasma sample or fraction thereof is at least 1 kU / L. For example, if anti-FcεRI IgE is present in the plasma sample or fraction thereof at a concentration of at least 0.1 kU / L (i.e., in a detectable amount), the plasma sample or fraction is not suitable for administration to an individual or for use in the production of an Ig preparation for administration to an individual.For example, if anti-FcεRI IgE is present in the plasma sample or fraction thereof at a concentration lower than 0.1 kU / L (i.e., not in a detectable quantity), the plasma sample or fraction thereof is suitable for administration to an individual or for use in the production of an Ig preparation for administration to an individual.

[0122] In one example, the method further includes determining the proportion of activation and / or degranulation of basophils and / or mast cells induced by the plasma sample or a fraction thereof. In another example, the method further includes determining the proportion of activation and / or degranulation of basophils and mast cells induced by the plasma sample or a fraction thereof. In yet another example, the method further includes determining the proportion of activation and / or degranulation of basophils or mast cells induced by the plasma sample or a fraction thereof.

[0123] In one example, the ratio of activation and / or degranulation of basophils and / or mast cells after exposure to the plasma sample or fraction. Petition 870250100974, dated 04 / 11 / 2025, page 25 / 216 20 / 172 of it is determined by determining the proportion of basophils and / or mast cells that express one or more selected markers from the group consisting of CD63, CD203c, CD107a, and combinations thereof. In one example, the activation ratio of basophils and mast cells after exposure to a plasma sample or fraction thereof is determined by determining the proportion of basophils and mast cells that express one or more selected markers from the group consisting of CD63, CD203c, CD107a, and combinations thereof. In one example, the activation ratio of basophils after exposure to a plasma sample or fraction thereof is determined by determining the proportion of basophils that express one or more selected markers from the group consisting of CD63, CD203c, and combinations thereof.

[0124] In one example, the proportion of mast cell activation after exposure to a plasma sample or fraction thereof is determined by determining the proportion of mast cells that express CD107a.

[0125] In one example, the method comprises determining the proportion of basophils expressing CD63 after exposure to a plasma sample or fraction thereof. For example, the method comprises determining a detectable amount of anti-FcεRI Ig in a plasma sample or fraction thereof by determining the proportion of basophils expressing CD63 after exposure to a plasma sample or fraction thereof. In one example, the proportion of basophils expressing CD63 after exposure to a plasma sample or fraction thereof is greater than 5%. For example, the proportion of basophils expressing CD63 is relative to the total proportion of basophils exposed to the plasma sample or fraction thereof. In one example, a detectable amount of anti-FcεRI Ig is present in the plasma sample or plasma fraction if at least 5% of a basophil population expresses CD63 after exposure to a plasma sample or plasma fraction.

[0126] In one example, the method comprises determining the proportion of basophils that express CD203c after exposure to the sample. Petition 870250100974, dated 04 / 11 / 2025, page 26 / 216 21 / 172 of plasma or a fraction thereof. For example, the method comprises determining a detectable amount of anti-FcεRI Ig in a plasma sample or fraction thereof by determining the proportion of basophils expressing CD203c after exposure to the plasma sample or a fraction thereof. In one example, the proportion of basophils expressing CD203c after exposure to the plasma sample or a fraction thereof is greater than 5%. For example, the proportion of basophils expressing CD203c is relative to the total proportion of basophils exposed to the plasma sample or a fraction thereof. In one example, a detectable amount of anti-FcεRI Ig is present in the plasma sample or a fraction of plasma if at least 5% of a basophil population expresses CD203c after exposure to the plasma sample or a fraction of plasma.

[0127] In one example, the method comprises determining the proportion of mast cells expressing CD107a after exposure to a plasma sample or fraction thereof. For example, the method comprises determining a detectable amount of anti-FcεRI Ig in a plasma sample or fraction thereof by determining the proportion of mast cells expressing CD107a after exposure to a plasma sample or fraction thereof. In one example, the proportion of mast cells expressing CD107a after exposure to a plasma sample or fraction thereof is greater than 5%. For example, the proportion of mast cells expressing CD107a is relative to the total proportion of mast cells exposed to the plasma sample or fraction thereof. In one example, a detectable amount of anti-FcεRI Ig is present in the plasma sample or plasma fraction if at least 5% of a mast cell population expresses CD107a after exposure to a plasma sample or plasma fraction.

[0128] In one example, the plasma sample or fraction thereof is selected from the group consisting of a human blood plasma sample, an IgG intermediate product, an intravenous immunoglobulin G (IVIG), a subcutaneous immunoglobulin G (SCIG), a plasma Petition 870250100974, dated 04 / 11 / 2025, page 27 / 216 22 / 172 rich in cryo, a cryo-poor plasma, a supernatant I (SN I), a Cohn Fraction II (Fr II), a Cohn Fraction II+III (Fr II+III), a Cohn Fraction I+II+III (FrI+II+III), a Kistler / Nitschmann Precipitate A (KN A), a Kistler / Nitschmann Precipitate B (KN B), a Kistler / Nitschmann Precipitate B from the Supernatant (KN B+1) and combinations thereof.

[0129] In one example, the plasma sample or fraction thereof is a sample of human blood plasma from one or more individuals.

[0130] In one example, the method further comprises administering the plasma sample or a fraction thereof to an individual if anti-FcεRI Ig is not present. For example, anti-FcεRI Ig is not present in a detectable quantity.

[0131] In one example, the method further comprises including the plasma sample or a fraction thereof in a combined blood plasma sample if anti-FcεRI Ig is not present. For example, the plasma sample or a fraction thereof is included in a combined blood plasma sample if anti-FcεRI Ig is not present in a detectable quantity.

[0132] In one example, the method further includes excluding the plasma sample or a fraction thereof from a pooled blood plasma sample if anti-FcεRI Ig is present. For example, the plasma sample or a fraction thereof is excluded from a pooled blood plasma sample if anti-FcεRI Ig is present in a detectable quantity.

[0133] The inventors' discoveries also provide the basis for a method of preparing a reduced preparation of Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) from a plasma sample or a fraction thereof, the method comprising detecting anti-FcεRI Ig in the plasma sample or a fraction thereof according to any method described in this document and producing a reduced preparation of anti-FcεRI Ig.

[0134] The present invention also offers a method of preparing a reduced preparation of Fc epsilon I receptor immunoglobulin (Ig). Petition 870250100974, dated 04 / 11 / 2025, p. 28 / 216 23 / 172 (FcεRI) from a plasma sample or a fraction thereof, the method comprising binding anti-FcεRI Ig to a chromatography resin comprising a ligand that binds to anti-FcεRI Ig in the plasma sample or a fraction thereof and collecting the reduced anti-FcεRI Ig preparation. The present invention also provides a method for preparing a reduced anti-Fc epsilon I receptor immunoglobulin (Ig) preparation from a plasma sample or a fraction thereof, the method comprising:

[0135] (i) loading the plasma sample or a fraction thereof onto a chromatography resin containing a ligand that binds to anti-FcεRI Ig in the plasma sample or a fraction thereof; and

[0136] (ii) collect the reduced anti-FcεRI Ig preparation.

[0137] In one example, the chromatography resin is an affinity chromatography resin. For example, a continuous affinity chromatography resin.

[0138] The present invention provides a method for preparing a reduced preparation of Fc epsilon I antireceptor immunoglobulin (Ig) (FcεRI) from a plasma sample or a fraction thereof, the method comprising:

[0139] (i) loading the plasma sample or a fraction thereof onto an affinity chromatography resin containing a ligand that binds to antiFcεRI Ig in the plasma sample or a fraction thereof; and

[0140] (ii) collect a reduced anti-FcεRI Ig preparation.

[0141] In one example, the ligand is immobilized in a chromatography resin matrix.

[0142] In one example, the ligand comprises FcεRI or a fragment or epitope thereof. For example, the FcεRI fragment comprises an α chain of FcεRI. In another example, the FcεRI fragment is a functional fragment. For example, the functional FcεRI fragment is a fragment of FcεRI that, when bound to anti-FcεRI Ig, activates an FcεRI-mediated signaling pathway. Petition 870250100974, dated 04 / 11 / 2025, p. 29 / 216 24 / 172

[0143] In one example, the method further comprises detecting the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof by performing a detection method as described in this document.

[0144] In one example, the reduced anti-FcεRI Ig preparation induces reduced activation of an FcεRI-mediated signaling pathway compared to a preparation in which the anti-FcεRI Ig level is not reduced. In another example, the reduced anti-FcεRI Ig preparation does not induce activation of an FcεRI-mediated signaling pathway.

[0145] In one example, the reduced anti-FcεRI Ig preparation induces a reduction in basophil and mast cell activation and / or degranulation compared to a preparation in which the anti-FcεRI Ig level is not reduced. In one example, the reduced anti-FcεRI Ig preparation induces a reduction in basophil activation compared to a preparation in which the anti-FcεRI Ig level is not reduced. In one example, the reduced anti-FcεRI Ig preparation induces a reduction in mast cell activation compared to a preparation in which the anti-FcεRI Ig level is not reduced. In one example, the reduced anti-FcεRI Ig preparation does not induce basophil and / or mast cell activation and / or degranulation.

[0146] In one example, the activation and / or degranulation of basophils and / or mast cells after exposure to a reduced anti-FcεRI Ig preparation is determined by a method described in this document. For example, the method comprises determining the proportion of basophils and / or mast cells expressing one or more selected markers from the group consisting of CD63, CD203c, CD107a and their combinations. In another example, the activation of basophils after exposure to a reduced anti-FcεRI Ig preparation is determined by determining the proportion of basophils expressing one or more selected markers from the group consisting of CD63, CD203c and their combinations. In yet another example, the activation of mast cells after exposure to a reduced anti-FcεRI Ig preparation is Petition 870250100974, dated 04 / 11 / 2025, page 30 / 216 25 / 172 determined by determining the proportion of mast cells that express CD107a.

[0147] In one example, the method comprises determining the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation. For example, the method comprises determining whether a detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation by determining the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation. In one example, the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 5%. For example, the proportion of basophils expressing CD63 is relative to the total proportion of basophils exposed to the reduced anti-FcεRI Ig preparation. In one example, a detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation if at least 5% of a basophil population expresses CD63 after exposure to the reduced anti-FcεRI Ig preparation.In one example, no detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation if less than 5% of a basophil population expresses CD63 after exposure to the reduced anti-FcεRI Ig preparation.

[0148] In one example, the method comprises determining the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation. For example, the method comprises determining whether a detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation by determining the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation. In one example, the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 5%. For example, the proportion of basophils expressing CD203c is relative to the total proportion of basophils exposed to the reduced anti-FcεRI Ig preparation. In one example, a detectable amount of anti-FcεRI Ig is present Petition 870250100974, dated 04 / 11 / 2025, p. 31 / 216 26 / 172 in the reduced anti-FcεRI Ig preparation if at least 5% of a basophil population expresses CD203c after exposure to the reduced anti-FcεRI Ig preparation. In one example, no detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation if less than 5% of a basophil population expresses CD203c after exposure to the reduced anti-FcεRI Ig preparation.

[0149] In one example, the method comprises determining the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation. For example, the method comprises determining whether a detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation by determining the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation. In one example, the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 5%. For example, the proportion of mast cells expressing CD107a is relative to the total proportion of mast cells exposed to the reduced anti-FcεRI Ig preparation. In one example, a detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation if at least 5% of a mast cell population expresses CD107a after exposure to the reduced anti-FcεRI Ig preparation.In one example, no detectable amount of anti-FcεRI Ig is present in the reduced anti-FcεRI Ig preparation if less than 5% of a mast cell population expresses CD107a after exposure to the reduced anti-FcεRI Ig preparation.

[0150] In one example, the reduced anti-FcεRI Ig preparation comprises less than 40 μg / mL of an anti-FcεRI IgG and less than 0.1 kU / L of an anti-FcεRI IgE.

[0151] In one example, the method comprises determining the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation. For example, the method comprises determining whether a detectable amount of anti-FcεRI IgG is present in the reduced anti-FcεRI Ig preparation. In a Petition 870250100974, dated 04 / 11 / 2025, p. 32 / 216 27 / 172 For example, the detectable amount of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is at least 40 μg / mL. In another example, the reduced anti-FcεRI Ig preparation comprises less than 40 μg / mL of anti-FcεRI IgG. In one example, the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is less than 35 μg / mL. In one example, the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is less than 30 μg / mL. In one example, the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is less than 35 μg / mL. In one example, the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is less than 20 μg / mL. In one example, the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is less than 15 μg / mL. In one example, the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is less than 10 μg / mL. In one example, the level of anti-FcεRI IgG in the reduced anti-FcεRI Ig preparation is less than 5 μg / mL.For example, if anti-FcεRI IgG is present in the reduced anti-FcεRI Ig preparation at a concentration lower than 40 μg / mL (i.e., not in a detectable quantity), the reduced anti-FcεRI Ig preparation is suitable for administration to the individual.

[0152] In one example, the method comprises determining the level of anti-FcεRI IgE in the reduced anti-FcεRI Ig preparation. For example, the method comprises determining whether a detectable amount of anti-FcεRI IgE is present in the reduced anti-FcεRI Ig preparation. In one example, the detectable amount of anti-FcεRI IgE in the reduced anti-FcεRI Ig preparation is at least 0.1 kU / L. In one example, the reduced anti-FcεRI Ig preparation comprises less than 0.1 kU / L of anti-FcεRI IgE. In one example, the level of anti-FcεRI IgE in the reduced anti-FcεRI Ig preparation is less than 0.01 kU / L. In one example, the level of anti-FcεRI IgE in the reduced anti-FcεRI Ig preparation is less than 0.05 kU / L. In one example, the level of anti-FcεRI IgE in the reduced anti-FcεRI Ig preparation is less than 0.001 kU / L. In one example, the level of anti-FcεRI IgE in the reduced anti-FcεRI Ig preparation is less than 0.005 kU / L. In one Petition 870250100974, dated 04 / 11 / 2025, p. 33 / 216 28 / 172 For example, if anti-FcεRI IgE is present in the reduced anti-FcεRI Ig preparation at a concentration less than 0.1 kU / L (i.e., not in a detectable amount), the reduced anti-FcεRI Ig preparation is suitable for administration to the individual.

[0153] In one example, the reduced anti-FcεRI Ig preparation is a reduced anti-FcεRI Ig IgG preparation.

[0154] In one example, the affinity chromatography resin further comprises a blood group A antigen and a blood group B antigen immobilized on the affinity chromatography resin matrix. In another example, the affinity chromatography resin further comprises a blood group A antigen. In yet another example, the affinity chromatography resin further comprises a blood group B antigen.

[0155] In one example, the affinity chromatography resin is a continuous affinity chromatography resin. For example, the continuous affinity chromatography resin comprises a ligand that binds to anti-FcεRI Ig.

[0156] In one example, the affinity chromatography resin is a continuous affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig, a blood group A antigen, and a blood group B antigen.

[0157] In one example, the affinity chromatography resin is a continuous affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig and a blood group A antigen immobilized in an affinity chromatography resin matrix.

[0158] In one example, the affinity chromatography resin is a continuous affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig and to a blood group B antigen immobilized in an affinity chromatography resin matrix.

[0159] The present invention provides a chromatography resin for Petition 870250100974, dated 04 / 11 / 2025, p. 34 / 216 29 / 172 affinity comprising a ligand that binds to anti-FcεRI Ig and, optionally, to a blood group A antigen and / or a blood group B antigen. For example, the description provides a continuous affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig and, optionally, to a blood group A antigen and / or a blood group B antigen.

[0160] In one example, affinity chromatography is a continuous affinity chromatography comprising:

[0161] (i) a first affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a first affinity chromatography resin matrix; and

[0162] (ii) a second affinity chromatography resin comprising a blood group A antigen and a blood group B antigen immobilized on a matrix of the second affinity chromatography resin.

[0163] In one example, affinity chromatography is a continuous affinity chromatography comprising:

[0164] (i) a first affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a first affinity chromatography resin matrix; and

[0165] (ii) a second affinity chromatography resin comprising a blood group A antigen immobilized on a matrix of the second affinity chromatography resin.

[0166] In one example, affinity chromatography is a continuous affinity chromatography comprising:

[0167] (i) a first affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a first affinity chromatography resin matrix; and

[0168] (ii) a second affinity chromatography resin comprising a blood group B antigen immobilized on a matrix Petition 870250100974, dated 04 / 11 / 2025, page 35 / 216 30 / 172 of the second affinity chromatography resin.

[0169] In one example, affinity chromatography is a continuous affinity chromatography comprising:

[0170] (i) a first affinity chromatography resin comprising a blood group A antigen and a blood group B antigen immobilized on a first affinity chromatography resin matrix; and

[0171] (ii) a second affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a matrix of the second affinity chromatography resin.

[0172] In one example, affinity chromatography is a continuous affinity chromatography comprising:

[0173] (i) a first affinity chromatography resin comprising a blood group A antigen immobilized on a first affinity chromatography resin matrix; and

[0174] (ii) a second affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a matrix of the second affinity chromatography resin.

[0175] In one example, affinity chromatography is a continuous affinity chromatography comprising:

[0176] (i) a first affinity chromatography resin comprising a blood group B antigen immobilized on a first affinity chromatography resin matrix; and

[0177] (ii) a second affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a matrix of the second affinity chromatography resin.

[0178] In one example, the ligand comprises FcεRI or a fragment or epitope thereof. For example, the FcεRI fragment comprises an α chain of FcεRI. In another example, the FcεRI fragment is a functional fragment. For example, the functional fragment FcεRI is a fragment of FcεRI that, Petition 870250100974, dated 04 / 11 / 2025, p. 36 / 216 When bound to anti-FcεRI Ig, 31 / 172 activates an FcεRI-mediated signaling pathway.

[0179] In one example, the method further comprises one or more steps selected from a group consisting of ethanol precipitation, octanoid acid fractionation, ion exchange chromatography, viral inactivation, viral filtration, ultrafiltration / diafiltration and combinations thereof.

[0180] The findings also provide the basis for a pharmaceutical composition comprising the reduced anti-FcεRI Ig preparation or the reduced anti-FcεRI Ig IgG plasma preparation, comprising polyclonal IgG, as well as the use of the pharmaceutical composition to treat, prevent and / or delay the progression of a condition (e.g., primary immunodeficiency disease, chronic inflammatory demyelinating polyneuropathy and chronic immune thrombocytopenic purpura) in an individual.

[0181] The present invention provides a pharmaceutical composition comprising a reduced immunoglobulin (Ig) anti-Fc epsilon I receptor (FcεRI) preparation produced by a method described in this document.

[0182] In one example, the polyclonal IgG is selected from the group consisting of Hizentra® (CSL Behring), Privigen® (CSL Behring), Flebogamma® (Grifols), Gamunex®-C (Grifols), Gammagard® (Takeda) and Octagam® (Octapharma). Gamunex®-C (Grifols), Xembify® (Grifols), Cutaquig® (Octapharma) and Cuvitru® (Takeda).

[0183] In one example, the reduced anti-FcεRI Ig preparation comprises an undetectable amount of anti-FcεRI Ig. For example, the reduced anti-FcεRI Ig preparation comprises less than 40 μg / mL of anti-FcεRI IgG and / or less than 0.1 kU / L of anti-FcεRI IgE. In one example, the reduced anti-FcεRI Ig preparation comprises less than 40 μg / mL of anti-FcεRI IgG. In one example, the reduced anti-FcεRI Ig preparation comprises less than 35 μg / mL of anti-FcεRI IgG. In one example, the reduced anti-FcεRI Ig preparation comprises less than 30 μg / mL of Petition 870250100974, dated 04 / 11 / 2025, p. 37 / 216 32 / 172 IgG anti-FcεRI. In one example, the reduced Ig anti-FcεRI preparation comprises less than 25 μg / mL of IgG anti-FcεRI. In one example, the reduced Ig anti-FcεRI preparation comprises less than 20 μg / mL of IgG anti-FcεRI. In one example, the reduced Ig anti-FcεRI preparation comprises less than 15 μg / mL of IgG anti-FcεRI. In one example, the reduced Ig anti-FcεRI preparation comprises less than 10 μg / mL of IgG anti-FcεRI. In one example, the reduced Ig anti-FcεRI preparation comprises less than 5 μg / mL of IgG anti-FcεRI. In one example, the reduced anti-FcεRI IgE preparation comprises less than 0.1 kU / L of anti-FcεRI IgE. In one example, the reduced anti-FcεRI IgE preparation comprises less than 0.01 kU / L of anti-FcεRI IgE. In one example, the reduced anti-FcεRI IgE preparation comprises less than 0.005 kU / L of anti-FcεRI IgE. In one example, the reduced anti-FcεRI IgE preparation comprises less than 0.001 kU / L of anti-FcεRI IgE.

[0184] In one example, the reduced anti-FcεRI Ig IgG preparation comprises an undetectable amount of anti-FcεRI Ig. For example, the reduced anti-FcεRI Ig IgG preparation comprises less than 40 μg / mL of anti-FcεRI IgG and / or less than 0.1 kU / L of anti-FcεRI IgE. In one example, the reduced anti-FcεRI Ig IgG preparation comprises less than 40 μg / mL of anti-FcεRI IgG. In one example, the reduced anti-FcεRI Ig IgG preparation comprises less than 35 μg / mL of anti-FcεRI IgG. In one example, the reduced anti-FcεRI Ig IgG preparation comprises less than 30 μg / mL of anti-FcεRI IgG. In one example, the reduced IgG anti-FcεRI preparation comprises less than 25 μg / mL of anti-FcεRI IgG. In another example, the reduced IgG anti-FcεRI preparation comprises less than 20 μg / mL of anti-FcεRI IgG. In another example, the reduced IgG anti-FcεRI preparation comprises less than 15 μg / mL of anti-FcεRI IgG.In one example, the reduced IgG anti-FcεRI Ig preparation comprises less than 10 μg / mL of anti-FcεRI IgG. In another example, the reduced IgG anti-FcεRI Ig preparation comprises less than 5 μg / mL. Petition 870250100974, dated 04 / 11 / 2025, p. 38 / 216 33 / 172 of IgG anti-FcεRI. In one example, the reduced IgG anti-FcεRI preparation comprises less than 0.1 kU / L of IgE anti-FcεRI. In one example, the reduced IgG anti-FcεRI preparation comprises less than 0.01 kU / L of IgE anti-FcεRI. In one example, the reduced IgG anti-FcεRI preparation comprises less than 0.005 kU / L of IgE anti-FcεRI. In one example, the reduced IgG anti-FcεRI preparation comprises less than 0.001 kU / L of IgE anti-FcεRI.

[0185] In one example, the reduced anti-FcεRI Ig preparation does not induce activation of the FcεRI-mediated signaling pathway. For example, the reduced anti-FcεRI Ig preparation does not induce activation and / or degranulation of basophils and / or mast cells. In one example, the reduced anti-FcεRI Ig preparation does not induce a detectable amount of activation and / or degranulation of basophils and / or mast cells.

[0186] The description contained herein makes it clear that the activation and / or degranulation of basophils and / or mast cells is determined by determining the proportion of basophils expressing CD63 and / or CD203c and / or mast cells expressing CD107a. In one example, the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5%, the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5%, and / or the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils and / or mast cells exposed to the reduced IgG anti-FcεRI Ig preparation. In another example, the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.In another example, the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation. Petition 870250100974, dated 04 / 11 / 2025, p. 39 / 216 34 / 172 In one example, the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total mast cell population exposed to the reduced IgG anti-FcεRI Ig preparation. In another example, the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total basophil population exposed to the reduced IgG anti-FcεRI Ig preparation and / or the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total basophil population exposed to the reduced IgG anti-FcεRI Ig preparation.In one example, the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation and / or the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of mast cells exposed to the reduced IgG anti-FcεRI Ig preparation. In one example, the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation and / or the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of mast cells exposed to the reduced IgG anti-FcεRI Ig preparation.In one example, the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation, the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation, and / or the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the population. Petition 870250100974, dated 04 / 11 / 2025, p. 40 / 216 35 / 172 total mast cells exposed to the reduced IgG preparation of anti-FcεRI Ig.

[0187] The present invention also offers a combined IgG preparation, wherein the combined IgG preparation comprises a detectable amount of Fc epsilon I receptor immunoglobulin (Ig) (FcεRI). To the expert, from the description in this document, it will be evident that the combined IgG preparation with a detectable amount of anti-FcεRI Ig has not been subjected to any method of the present invention. Thus, the present invention also offers a method for detecting anti-FcεRI Ig in a combined IgG preparation.

[0188] The present invention also provides a method for treating, preventing and / or delaying the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual, the method comprising administering the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation or the pharmaceutical composition described in this document. For example, the description provides a method for treating a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual, the method comprising administering the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation or the pharmaceutical composition described in this document.The description also offers a method for preventing a condition related to immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual, the method comprising administering the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation, or the pharmaceutical composition described in this document. The description also offers a method for delaying the progression of a condition related to immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual, the method comprising administering the preparation. Petition 870250100974, dated 04 / 11 / 2025, p. 41 / 216 36 / 172 reduced anti-FcεRI Ig, from the reduced anti-FcεRI Ig IgG preparation or from the pharmaceutical composition described in this document.

[0189] The present invention also provides reduced preparation of The description provides for the reduced Ig anti-FcεRI preparation, the reduced IgG preparation of Ig anti-FcεRI, or the pharmaceutical composition described herein for use in the treatment, prevention, and / or delay of the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual. The description also provides for the reduced Ig anti-FcεRI preparation, the reduced IgG preparation of Ig anti-FcεRI, or the pharmaceutical composition described herein for use in the treatment of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual. The description also provides for the reduced Ig anti-FcεRI preparation, the reduced IgG preparation of Ig anti-FcεRI, or the pharmaceutical composition described herein for use in the prevention of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual.The description also provides for the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig preparation, or the pharmaceutical composition described herein for use in delaying the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual.

[0190] The present invention also provides the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation, or the pharmaceutical composition described herein to treat, prevent, and / or delay the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual. The present invention also provides the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation, or the pharmaceutical composition described herein. Petition 870250100974, dated 04 / 11 / 2025, p. 42 / 216 37 / 172 document to treat a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual. The present invention also provides the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation or the pharmaceutical composition described herein to prevent a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual. The present invention also provides the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation or the pharmaceutical composition described herein to delay the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual.

[0191] The present invention also allows the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation, or the pharmaceutical composition described herein in the manufacture of a medicament for the treatment, prevention, and / or delaying of the progression of an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual. The present invention also allows the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation, or the pharmaceutical composition described herein in the manufacture of a medicament for the treatment of an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual.The present invention also allows the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation, or the pharmaceutical composition described herein in the manufacture of a medicament for the prevention of an immunodeficiency, an inflammatory disease, an autoimmune disease, and / or an acute infection in an individual. The present invention also allows the use of the reduced anti-FcεRI Ig preparation, the reduced anti-FcεRI Ig IgG preparation. Petition 870250100974, dated 04 / 11 / 2025, p. 43 / 216 38 / 172 Ig anti-FcεRI or the pharmaceutical composition described in this document in the manufacture of a medicament to delay the progression of an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual.

[0192] The present invention also offers a method for preparing an immunoglobulin (Ig) preparation from a plasma sample or a fraction thereof, the preparation of Ig with reduced adverse reactions in an individual, the method which includes detecting the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof according to any method described herein and producing an Ig preparation with reduced adverse reactions.

[0193] In one example, the condition is selected from the group consisting of primary immunodeficiency disease, chronic inflammatory demyelinating polyneuropathy, and chronic immune thrombocytopenic purpura. In one example, the condition is primary immunodeficiency disease. In another example, the condition is chronic inflammatory demyelinating polyneuropathy. In another example, the condition is chronic immune thrombocytopenic purpura.

[0194] The present invention also offers a method for preparing an immunoglobulin (Ig) preparation from a plasma sample or a fraction thereof, the Ig preparation which reduced adverse reactions in an individual, the method comprising determining the proportion of activation and / or degranulation of basophils and / or mast cells after exposure to the plasma sample or a fraction thereof;

[0195] (i) include the sample or plasma fraction in the Ig preparation if the proportion of basophils expressing CD63 after exposure to the sample or plasma fraction is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total population of basophils exposed to the sample or plasma fraction;

[0196] (ii) exclude the plasma sample or fraction thereof from the preparation of Petition 870250100974, dated 04 / 11 / 2025, page 44 / 216 39 / 172 If the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction thereof is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14%, or greater than 15% of the total population of basophils exposed to the plasma sample or fraction thereof;

[0197] (iii) include the sample or plasma fraction in the Ig preparation if the proportion of basophils expressing CD203c after exposure to the sample or plasma fraction is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total population of basophils exposed to the sample or plasma fraction;

[0198] (iv) exclude the plasma sample or a fraction thereof in the preparation of If the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction thereof is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14%, or greater than 15% of the total population of basophils exposed to the plasma sample or fraction thereof;

[0199] (v) include the plasma sample or a fraction thereof in the preparation of Ig if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction thereof is less than 1%, less than 2%, less than 3%, less than 4%, or less than 5% of the total mast cell population exposed to the plasma sample or fraction thereof; and / or

[0200] (vi) exclude the plasma sample or a fraction thereof in the preparation of Ig if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction thereof is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14%, or greater than 15% of the total mast cell population exposed to the plasma sample or fraction thereof.

[0201] The present invention also provides methods for identifying a suitable plasma donation for the production of an Ig preparation. Petition 870250100974, dated 04 / 11 / 2025, p. 45 / 216 40 / 172 BRIEF DESCRIPTION OF THE DRAWINGS

[0202] Figure 1 is a graphical representation of an activation profile mediated by the MRGPRX2 receptor for Cortistatin 14 (A, positive control), individual plasma donors (B, C, including donor Z), affected (D, F) and unaffected (E, G) products.

[0203] Figure 2 is a graphical representation of Hoxb8 mast cell activation by IVIG. Unaffected batches labeled Ctrl-P. Affected batches labeled AE-P (A) or unlabeled (B). The formulation buffer is used as a negative control (data not shown).

[0204] Figure 3 is a graphical representation of a Hoxb8 mast cell activation by SCIG. Unaffected batches labeled Ctrl-H. Affected batches labeled AE-H(A) or unlabeled (B). The formulation buffer is used as a negative control (data not shown).

[0205] Figure 4 is a graphical representation of the mast cell activation profiles for 17 single donor plasma samples tested (A, B). Plasma 1 sample is from designated donor Z. The arrow indicates the activation signal of Plasma 1.

[0206] Figure 5 is a graphical representation of mast cell activation profiles for untreated (A), IgG-depleted (B), and IgE-depleted (C) plasma from donors 1, 2, and 3. Exclamation points indicate the absence of Hoxb8 mast cell activation.

[0207] Figure 6 is a graphical representation of mast cell activation profiles with IgG binding blockade to FcYRIIb by the Fc-based antiCD16 / 32 antibody. The dashed line highlights the 5% threshold.

[0208] Figure 7 is a graphical representation of mast cell activation profiles with IgE binding to FcεRIα blocked by soluble FcεRIα. Exclamation points indicate partial blockage of Hoxb8 mast cell activation. The dashed line highlights the 5% threshold.

[0209] Figure 8 is a graphical representation of mast cell activation profiles with an intrinsic cell block, targeting BTK with Petition 870250100974, dated 04 / 11 / 2025, page 46 / 216 41 / 172 Ibrutinib. Exclamation points indicate the suppression of Hoxb8 mast cell activation. The dotted line highlights the 5% limit.

[0210] Figure 9 is a graphical representation of mast cell activation profiles with blockade of C5a-dependent mast cell activation by the use of the antagonist C5aR. The dashed line highlights the 5% threshold.

[0211] Figure 10 is a graphical representation of the activation of basophil (CD63+) degranulation by IVIG using basophils from Donors 1 (A), 2 (B), 3 (C). Unaffected batches labeled Ctrl-P. Affected batches labeled AE-P or unlabeled. The upper dashed line highlights the 5% limit and the lower dashed line highlights the baseline.

[0212] Figure 11 is a graphical representation of the activation of basophil (CD63+) degranulation by SCIG using basophils from basophil donors 1 (A), 2 (B), 3 (C). Unaffected batches labeled Ctrl-H. Affected batches labeled AE-H. The upper dashed line highlights the 5% limit and the lower dashed line highlights the baseline.

[0213] Figure 12 is a graphical representation of the activation of basophil (CD63+) degranulation by individual plasma samples using basophils from Donors 1 (A), 2 (B), 3 (C). Plasma 1 sample is from designated donor Z. The arrows indicate the activation signal of Plasma 1 for all basophil donors in the undiluted condition. The upper dashed line highlights the 5% threshold and the lower dashed line highlights the baseline.

[0214] Figure 13 is a graphical representation of the activation of basophil degranulation, CD63+ (A) and CD203c+ (B) without IL-3 by individual plasma samples using basophils from Donor 1. The dashed line highlights the 5% threshold.

[0215] Figure 14 is a graphical representation of the activation of CD63+ (A) and CD203c+ (B) basophil degranulation without IL-3 by individual plasma samples using basophils from Basophil Donor 2. The dashed line highlights the 5% threshold. Petition 870250100974, dated 04 / 11 / 2025, page 47 / 216 42 / 172

[0216] Figure 15 is a graphical representation of the activation of CD63+ (A) and CD203c+ (B) basophil degranulation without IL-3 by individual plasma samples using basophils from Basophil Donor 3. The dashed line highlights the 5% threshold.

[0217] Figure 16 is a graphical representation of the activation of basophil degranulation (CD203c+) by SCIG (A) and IVIG (B) using donor basophils 1. The upper dashed line highlights the 5% limit and the lower dashed line highlights the baseline. The exclamation point indicates that the activation signal has exceeded the limit. For each batch, basophil degranulation activation is plotted from left to right at a concentration of SCIG (A) or IVIG (B) as used in the assay of 2, 20, 200, 2000, 20,000 and 40,000 pg / mL. For each batch on the right side of each panel, activation at a concentration of 2000 pg / mL of SCIG (A) or IVIG (B) enriched with anti-FcεRI is plotted as a stimulation control.

[0218] Figure 17 is a graphical representation of the activation of basophil degranulation (CD203c+) by SCIG (A) and IVIG (B) using donor basophils 2. The upper dashed line highlights the 5% limit and the lower dashed line highlights the baseline.For each batch, basophil degranulation activation is plotted from left to right at a concentration of SCIG (A) or IVIG (B) as used in the assay of 2, 20, 200, 2000, 20,000, and 40,000 pg / mL. For each batch on the right side of each panel, activation at a concentration of 2000 pg / mL of SCIG (A) or IVIG (B) enriched with anti-FcεRI is plotted as a stimulation control.

[0219] Figure 18 is a graphical representation of basophil (CD203c+) degranulation activation by SCIG (A) and IVIG (B) using donor basophils 3. The upper dashed line highlights the 5% limit and the lower dashed line highlights the baseline. For each batch, basophil degranulation activation is plotted from left to right at a concentration of SCIG (A) or IVIG (B) as used in the assay of 2, 20, 200, 2000, 20,000 and 40,000 pg / mL. For each batch on the right side of each. Petition 870250100974, dated 04 / 11 / 2025, page 48 / 216 43 / 172 panel, activation for a concentration of 2000 pg / mL of SCIG (A) or IVIG (B) enriched with anti-FcεRI is plotted as a stimulation control.

[0220] Figure 19 is a graphical representation of basophil (CD203c+) degranulation by individual plasma samples using basophils from Donors 1 (A), 2 (B), 3 (C). The upper dashed line highlights the 5% threshold, the lower dashed line highlights the baseline, with anti-FcεRI peak media (stimulation control). For each plasma sample using basophils from Donors 1 (A), 2 (B), 3 (C), basophil degranulation is plotted from left to right for the following plasma dilutions tested: undiluted, 1:10, 1:100, 1:1000, 1:10000, and 1:100000. For each plasma sample tested, on the right side of each panel, a 1:10 dilution labeled with anti-FcεRI is plotted as a stimulus control.

[0221] Figure 20 is a graphical representation of basophil (CD203c+) degranulation profiles for untreated, IgG-depleted, IgG-enriched, and IgE-depleted plasma from donors 1 (A, D, G), 2 (B, E, H), and 3 (C, F, I). Plasma 1 sample is from designated donor Z. The arrows indicate the cancellation of the activation signal from Plasma 1 for all basophils from IgG-depleted plasma donors. The upper dashed line highlights the 5% threshold, the lower dashed line highlights the baseline, signifying anti-FcεRI (stimulation control). DETAILED DESCRIPTION IN GENERAL

[0222] Throughout this descriptive report, unless specifically stated otherwise or the context requires otherwise, reference to a single step, matter composition, group of steps or group of matter compositions shall be considered as encompassing one and a plurality (i.e., one or more) of these steps, matter compositions, groups of steps or groups of matter compositions.

[0223] Those skilled in the art will understand that the present invention is susceptible to variations and modifications other than those specifically Petition 870250100974, dated 04 / 11 / 2025, page 49 / 216 44 / 172 described. It should be understood that the description includes all such variations and modifications. The description also includes all steps, features, compositions and compounds mentioned or indicated in this descriptive report, individually or collectively, and any and all combinations of said steps or features.

[0224] The present invention should not be limited in its scope by the specific examples described herein, which are intended for illustrative purposes only. Functionally equivalent products, compositions and methods are clearly within the scope of the present invention.

[0225] Any instance of the present invention contained herein shall be deemed applicable mutatis mutandis to any other instance of the description, unless specifically stated otherwise.

[0226] Unless specifically defined otherwise, all technical and scientific terms used herein should be considered as having the same meaning commonly understood by someone with ordinary skill in the field (e.g., in immunology, immunohistochemistry, protein chemistry, and biochemistry).

[0227] Unless otherwise indicated, the recombinant protein, cell culture, and immunological techniques used in the present invention are standard procedures, well known to those skilled in the art. These techniques are described and explained throughout the literature in sources such as J. Perbal, A Practical Guide to Molecular Cloning, John Wiley and Sons (1984), J. Sambrook et al. Molecular Cloning: A Laboratory Handbook, Cold Spring Harbour Laboratory Press (1989), TA Brown (editor), Essential Molecular Biology: A Practical Approach, Volumes 1 and 2, IRL Press (1991), DM Glover and BD Hames (editors), DNA Cloning: A Practical Approach, Volumes 1-4, IRL Press (1995 and 1996), and FM Ausubel et al. (editors), Current Protocols in Molecular Biology, Greene Pub. Associates and WileyInterscience (1988, including all updates to the present), Ed Harlow and David Lane (editors) Antibodies: A Laboratory Manual, Cold Spring Petition 870250100974, dated 04 / 11 / 2025, page 50 / 216 45 / 172 Harbour Laboratory, (1988), and JE Coligan et al. (editors) Current Protocols in Immunology, John Wiley & Sons (including all updates to the present).

[0228] The term “and / or”, for example, “X and / or Y” should be understood as meaning “X and Y” or “X or Y” and should be considered as providing explicit support for both meanings or for either meaning.

[0229] Throughout this descriptive report, the word “compreender”, or variations such as “compreende” or “compreendendo”, will be understood as implying the inclusion of an element, whole or stage, or group of elements, whole or stage, but not the exclusion of any other element, whole or stage, or group of elements, whole or stage. SELECTED DEFINITIONS

[0230] The term “immunoglobulin (Ig)” should be understood as a protein or antibody present in the serum and cells of the immune system. There are several types of Ig, for example, IgG, IgE, IgM, IgD, IgA, and IgY.

[0231] As used in this document, “an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI)” or “anti-FceRI Ig” should be understood as any Ig that binds to FcεRI, a fragment thereof, or an epitope of FceRI.

[0232] As used in this document, the term “FceRI-mediated signaling pathway” refers to the cross-linking of FceRI that leads to the activation and / or degranulation of basophils and / or mast cells.

[0233] The term “plasma” refers to the pale / light yellow component of blood obtained from one or more blood donors. The methods of obtaining plasma from a donor will be apparent to an experienced person and / or described in this document. For example, plasma is obtained by removing red blood cells from donated blood. For example, plasma is obtained by plasmapheresis.

[0234] The term “plasma sample” or “plasma fraction” refers to Petition 870250100974, dated 04 / 11 / 2025, p. 51 / 216 46 / 172 Plasma that has been fractionated to isolate one or more desirable protein components from the plasma. For example, plasma can be fractionated to isolate cryoprecipitates (proteins that precipitate from solution when a unit of fresh frozen plasma is slowly thawed in the cold) and cryosupernatant (also known as cryo-poor plasma). For example, plasma can be fractionated by ethanol precipitation to produce Oncley fractions containing IgG, Cohn fractions, ammonium sulfate precipitates, or Precipitate A (KN A) plasma, as described in U.S. Patent 3,301,842. Plasma fractions include precipitate II+III produced according to Cohn methods, such as Method 6, Cohn et al. J. Am; Chem. Soc., 68 (3), 459-475 (1946), Method 9, Oncley et al. J. Am; Chem. Soc., 71, 541-550 (1946), or the I+II+III precipitate, Method 10, Cohn et al. J. Am; Chem. Soc., 72, 465-474 (1950); as well as the method of Deutsch et al. J. Biol. Chem.164, 109-118 (1946) or the Nitschmann and Kistler Precipitate-A Vox Sang. 7, 414-424 (1962); Helv. Chim. Acta 37, 866873 (1954). For example, plasma can be fractionated by octanoic acid fractionation, as described in European application 893450. Typically, the Cohn fractions and the Kistler / Nitschmann Precipitate A (KN A) exist as a suspended paste. Other purification techniques, including chromatography, can be used.

[0235] As used in this document, an “IgG intermediate product” refers to any material obtained between manufacturing steps. For example, supernatants or fractions of the starting material.

[0236] As used in this document, “mast cells” are understood to refer to cells residing in granular tissues known for host cell response, allergic response, and vascular homeostasis.

[0237] As used in this document, “basophils” should be understood as the largest type of granulocyte, representing approximately 0.5% to 1% of circulating white blood cells. Their activation and degranulation are involved Petition 870250100974, dated 04 / 11 / 2025, page 52 / 216 47 / 172 in inflammatory reactions during the immune response, as well as in the formation of acute and chronic allergic diseases.

[0238] The term “protein” should be understood as a single polypeptide chain, that is, a series of contiguous amino acids linked by peptide bonds or a series of polypeptide chains linked together covalently or non-covalently (i.e., a polypeptide complex). For example, the series of polypeptide chains may be covalently linked using a suitable chemical or a disulfide bond. Examples of non-covalent bonds include hydrogen bonds, ionic bonds, Van der Waals forces, and hydrophobic interactions.

[0239] The term “polypeptide” or “polypeptide chain” will be understood in the previous paragraph as a series of contiguous amino acids linked by peptide bonds.

[0240] The specialist knows that an “antibody” is generally considered a protein comprising a variable region composed of a plurality of polypeptide chains, for example, a polypeptide comprising a variable light chain (VL) region and a polypeptide comprising a variable heavy chain (VH) region. In general, an antibody also comprises constant domains, some of which may be organized into a constant region, which includes a constant fragment or a crystallizable fragment (Fc), in the case of a heavy chain. A VH and a VL interact to form an Fv comprising an antigen-binding region capable of specifically binding to one or a few closely related antigens. In general, a mammalian light chain is a κ light chain or a λ light chain, and a mammalian heavy chain is α, δ, ε, γ, or μ.Antibodies can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgGa, IgG4, IgA1, and IgA2), or subclass. The term "antibody" also encompasses humanized antibodies, primate antibodies, and antibodies. Petition 870250100974, dated 04 / 11 / 2025, p. 53 / 216 48 / 172 human, synhumanized antibodies and chimeric antibodies.

[0241] As used in this document, “variable region” refers to the portions of the light and / or heavy chains of an antibody, as defined in this document, that are capable of specifically binding to an antigen and include amino acid sequences of complementarity-determining regions (CDRs), namely CDR1, CDR2, and CDR3, and structure regions (FRs). Exemplary variable regions comprise three or four FRs (e.g., FR1, FR2, FR3, and optionally FR4) along with three CDRs. VH refers to the variable region of the heavy chain. VL refers to the variable region of the light chain.

[0242] As used in this document, the term “detect” or “detect” refers to the identification of the presence or existence of an antiFcεRI Ig in a plasma sample.

[0243] As used in this document, the term “contact” or “contact” is used to refer to a direct or indirect interaction or association between a ligand or reagent described in this document and a molecule. For example, a ligand (such as FcεRI or a fragment or epitope thereof) binds directly or indirectly to an anti-FcεRI Ig in a sample or plasma fraction. The term also covers the interaction between, for example, a first protein (such as a detection protein) with, for example, a second molecule (such as an antibody).

[0244] As used in this document, the term “binds” in reference to the interaction of a protein with an antigen means that the interaction depends on the presence of a specific structure (e.g., an antigenic determinant or epitope) on the antigen. For example, an antibody recognizes and binds to a specific protein structure rather than to proteins in general. If an antibody binds to the epitope “A”, the presence of a molecule containing the epitope “A” (or free, unlabeled “A”), in a reaction containing labeled “A” and the antibody, will reduce the amount of labeled “A” bound to the antibody. Petition 870250100974, dated 04 / 11 / 2025, p. 54 / 216 49 / 172

[0245] As used in this document, the term “specifically binds” or “binds specifically” should be understood as an antibody of the description reacting or associating more frequently, more rapidly, for a longer duration, and / or with greater affinity to a particular antigen (e.g., S protein or RBD) than to alternative antigens. For example, an antibody binds to S protein or RBD with materially greater affinity (e.g., 20-fold or 40-fold or 60-fold or 80-fold to 100-fold or 150-fold or 200-fold greater affinity) avidity, more readily, and / or for a longer duration than it binds to other antigens, for example, to antigens commonly recognized by polyreactive natural antibodies (i.e., by naturally occurring antibodies known to bind to a variety of antigens found naturally in humans).In general, but not necessarily, reference to linkage means specific linkage, and each term should be understood as explicitly supporting the other term.

[0246] As used in this document, the term “epitope” (synonymous with “antigenic determinant”) should be understood as a region of the protein to which a protein comprising a variable antibody region binds. This term is not necessarily limited to the specific residues or structure with which the protein makes contact. For example, this term includes the region encompassing the amino acids contacted by the protein and / or 5-10 or 2-5 or 1-3 amino acids outside this region. In some examples, the epitope comprises a series of discontinuous amino acids that are positioned close to each other when the protein is folded, i.e., a “conformational epitope”. The expert also knows that the term “epitope” is not limited to peptides or polypeptides.For example, the term "epitope" includes chemically active surface clusters of molecules, such as sugar side chains, phosphorus side chains, or sulfonyl side chains, and in certain examples, may have specific three-dimensional structural features. Petition 870250100974, dated 04 / 11 / 2025, p. 55 / 216 50 / 172 and / or specific load characteristics.

[0247] The term “affinity chromatography resin” should be understood as a resin comprising an affinity chromatography ligand (e.g., FcεRI or fragment or epitope thereof) bound to a matrix, as would be apparent to the skilled craftsman and / or as described in this document.

[0248] The term “ligand” should be understood as a molecule immobilized in a chromatographic column matrix that interacts with anti-FcεRI Ig. For example, the ligand comprises an FcεRI or a fragment or epitope thereof. In one example, the ligand is an FcεRI or a fragment or epitope thereof. In another example, the ligand is an FcεRI antibody or a fragment thereof. In yet another example, the ligand is an FcεRI DNA aptamer.

[0249] The term “matrix” should be understood as a support to which molecules can be attached, directly or indirectly. The matrix may include any substrate material that is capable of providing physical support for the compositions described herein. The materials may be naturally occurring, synthetic, or a modification of a naturally occurring material.Suitable matrix materials may include glass fibers, polyester, cellulose, rayon, silicon, a silicon wafer chip, graphite, mirrored surfaces, laminates, membranes, ceramics, plastics (including polymers such as, for example, poly(vinyl chloride), cycloolefin copolymers, agarose gels or spheres, polyacrylamide, polyacrylate, polyethylene, polypropylene, poly(4-methylbutene), polystyrene, polymethacrylate, poly(ethylene terephthalate), polytetrafluoroethylene (PTFE or Teflon®), nylon, poly(vinyl butyrate)), germanium, gallium arsenide, gold, silver, Langmuir-Blodgett films, a flux chip, etc., used alone or in combination with other materials. Other rigid materials may be considered, such as glass, which includes silica and, in addition, includes, for example, glass that is available as Bioglass. Other materials that may be employed include... Petition 870250100974, dated 04 / 11 / 2025, page 56 / 216 51 / 172 porous materials, such as, for example, glass spheres with controlled pores, cross-linked agarose or Sepharose® resins, or cross-linked bis-acrylamide and azalactone copolymers.

[0250] The term “pharmaceutical composition” should be understood as an Ig formulation with compounds generally accepted in the art for the administration of Ig to mammals. Exemplary compounds include all pharmaceutically acceptable carriers, diluents, or excipients.

[0251] The term “treat”, “treatment” or “being treated” should be understood as the administration of a therapeutically effective amount of Ig such that one or more symptoms or features of the disease are reduced in the individual or that the individual is no longer clinically diagnosed with the disease.

[0252] The term “preventing”, “preventing” or “prevention” includes providing prophylaxis with respect to the occurrence or recurrence of a specific condition in an individual. An individual may be predisposed to or at risk of developing a condition, but has not yet been diagnosed with it.

[0253] As used in this document, the phrase “delay the progression of” includes reducing or slowing the progression of a condition in an individual and / or more than one symptom of the condition.

[0254] The term “condition” should be understood as a state of being or state of health of an individual who needs treatment with Ig.

[0255] The term “individuals” should be understood as any animal, including humans, for example, a mammal. Some examples include, but are not limited to, human beings and non-human primates. For example, the individual is a human being. Fc EPSILON I RECEPTOR (FceRI)

[0256] The present invention provides a method for identifying an anti-Fc epsilon I receptor immunoglobulin (Ig) (FccRI) in a plasma sample or a fraction thereof.

[0257] As used in this document, the term “FC Receiver” Petition 870250100974, dated 04 / 11 / 2025, p. 57 / 216 "52 / 172 epsilon I (FcεRI)" should be understood as an antigen present on mast cells, basophils, Langerhans epidermal cells, eosinophils, and other antigen-presenting cells. FcεRI is a multimeric receptor and a member of a family of antigen / Fc-related receptors that have conserved structural characteristics and similar functions in initiating intracellular signaling cascades. In humans, two types of FcεRI are expressed on the cell surface: a tetrameric receptor composed of an α chain, a β chain, and a homodimeric γ chain (αβγ2), and a trimeric receptor composed of an α chain and a homodimeric γ chain (αγ2).

[0258] The FcεRI is responsible for the activation and degranulation of mast cells and basophils. Antigenic cross-linking, for example, through the binding of IgE and / or IgG, of the FcεRI initiates several signaling pathways, termed the “FcεRI-mediated signaling pathway,” which control various effector responses. This includes the secretion of allergic mediators and the induction of cytokine gene transcription, resulting in the secretion of molecules such as interleukin-4, interleukin-6, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor. Therefore, the FcεRI is fundamental for the induction and maintenance of an allergic response. DETECTION, IDENTIFICATION AND SCREENING OF ANTI-FcεRI Ig

[0259] The present invention offers a method for detecting anti-FcεRI Ig in a plasma sample or a fraction thereof. In addition, the present invention offers a screening method for anti-FcεRI Ig in a plasma sample or a fraction thereof.

[0260] The present invention also provides methods for identifying a plasma sample or a fraction thereof suitable for administration to an individual. The present invention also provides methods for identifying a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual. In addition, the present invention provides methods for screening Petition 870250100974, dated 04 / 11 / 2025, page 58 / 216 53 / 172 a sample of plasma or a fraction thereof to determine suitability for administration to an individual. The present invention also provides methods for screening a sample of plasma or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual.

[0261] It is evident to the specialist that a plasma sample or fraction containing a detectable amount of anti-FcεRI Ig is not suitable for administration to an individual and / or for use in the production of an Ig preparation for administration to an individual.

[0262] As used in this document, a “detectable quantity” should be understood as any amount or quantity of anti-FcεRI Ig that induces activation of the FcεRI-mediated signaling pathway. For the expert, from the description in this document, it is evident that anti-FcεRI Ig may still be present in a plasma sample or fraction thereof, but in an insufficient quantity to induce activation of the FcεRI-mediated signaling pathway. For example, activation of the FcεRI-mediated signaling pathway may occur when there is more than 40 μg / mL of an anti-FcεRI IgG in a sample and / or more than 0.1 kU / L of an anti-FcεRI IgE in a sample.

[0263] In one example, the activation of the signaling pathway mediated by FcεRI can occur when the proportion of basophils expressing CD63 after exposure to a sample is greater than 5% of the total population of basophils exposed to the sample and / or the proportion of basophils expressing CD203c after exposure to a sample is greater than 5% of the total population of basophils exposed to the sample and / or the proportion of mast cells expressing CD107a after exposure to a sample is greater than 5% of the total population of mast cells exposed to the sample. For example, the proportion of basophils expressing CD63 and / or CD203c is relative to the total proportion of basophils exposed to the plasma sample or the plasma fraction. In one example, the proportion of mast cells expressing CD107a is relative to Petition 870250100974, dated 04 / 11 / 2025, page 59 / 216 54 / 172 total proportion of mast cells exposed to the plasma sample or a fraction thereof.

[0264] In alternative examples, a plasma sample or fraction thereof that does not contain a detectable amount of anti-FcεRI Ig is suitable for administration to the individual. For example, the method further includes administering the plasma sample to an individual if anti-FcεRI Ig is not present or is not detectable in the plasma sample or fraction thereof.

[0265] The present invention also provides methods for identifying an individual suitable for plasma donation for the production of an Ig preparation. In addition, the present invention provides methods for screening an individual suitable for plasma donation for the production of an Ig preparation. The present invention also provides methods for identifying a plasma donation suitable for the production of an Ig preparation.

[0266] It is evident to the specialist that a plasma sample or fraction from an individual that shows a detectable amount of anti-FcεRI Ig indicates that the individual is not a suitable candidate for plasma donation for the production of an Ig preparation. Furthermore, a plasma sample or fraction that shows a detectable amount of anti-FcεRI Ig indicates that the plasma sample or fraction is not suitable for the production of an Ig preparation.

[0267] In alternative examples, a plasma sample or fraction from the individual that does not contain a detectable amount of anti-FcεRI Ig indicates that the individual is a suitable candidate for plasma donation for the production of an Ig preparation. Furthermore, a plasma sample or fraction that does not show a detectable amount of anti-FcεRI Ig indicates that the plasma sample or fraction is suitable for the production of an Ig preparation. For example, the method further includes the donation of the plasma sample or fraction thereof for the production of an Ig preparation if a detectable amount of anti-FcεRI Ig is not present. Petition 870250100974, dated 04 / 11 / 2025, page 60 / 216 55 / 172

[0268] These detection, screening, and / or identification methods will be apparent to the qualified person and / or are described in this document. Exemplary methods for detection, screening, and / or identification of anti-FcεRI Ig in a plasma sample or fraction thereof or in an individual use ligands that bind to anti-Fc epsilon I receptor Ig (FcεRI) (e.g., an FcεRI or fragment or epitope thereof) and include a lateral flow assay and an ELISA. Methods for determining anti-FcεRI Ig levels will be apparent to the expert and / or described in this document.

[0269] In one example, the method comprises performing an enzyme-linked immunosorbent assay (ELISA). In another example, the method includes performing a fluorescence-linked immunosorbent assay (FLISA). In yet another example, the method comprises performing a lateral flow immunoassay. Enzyme-linked immunosorbent assay (ELISA) and fluorescence-linked immunosorbent assay (FLISA)

[0270] The present invention provides an ELISA or FLISA for detecting, identifying and / or tracking an anti-FcεRI Ig in a plasma sample or a fraction thereof, the assay comprising a ligand (e.g., an FcεRI or fragment or epitope thereof).

[0271] Standard solid-phase ELISA or FLISA formats are particularly useful for determining the concentration of a protein (e.g., an antibody or Ig) in a variety of samples. In one form, this assay involves immobilizing a biological sample in a solid matrix.

[0272] A ligand (e.g., an FcεRI or fragment or epitope thereof) that specifically binds to a protein (i.e., anti-FcεRI Ig) in a plasma sample or fraction thereof is brought into direct contact with the immobilized ligand and forms a direct bond with any target protein present in said sample. In general, this ligand is labeled with a Petition 870250100974, dated 04 / 11 / 2025, p. 61 / 216 56 / 172 detectable reporter molecule, such as, for example, a fluorescent marker (e.g., FITC or Texas Red) or a fluorescent semiconductor nanocrystal (as described in US 6,306,610) in the case of a FLISA or an enzyme (e.g., horseradish peroxidase (HRP) or alkaline phosphatase (AP) or β-galactosidase) in the case of an ELISA or an alternative protein labeled with a protein marker, e.g., horseradish peroxidase (HRP), alkaline phosphatase (AP) or β-galactosidase) in the case of an ELISA or, alternatively, a labeled protein or antibody that binds to the first antibody may be used. After washing to remove any unbound protein, the marker is detected directly, in the case of a fluorescent marker, or by adding a substrate, such as hydrogen peroxide, TMB or toluidine, or 5-bromo-4-chloro-3-indol-beta-D-galaotopyranoside (x-gal), in the case of an enzymatic marker.

[0273] These ELISA or FLISA-based systems are suitable for quantifying the amount of a protein in a sample by calibrating the detection system against known amounts of a standard to which the ligand binds, such as anti-FcεRI Ig.

[0274] The expert will understand that the method of the present invention is suitable for use in an enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassay (EIA). As used in this document, the term “ELISA”, “sandwich ELISA”, “capture ELISA” or “EIA” refers to the immobilization of a ligand (specific for anti-FcεRI Ig) on ​​a matrix, such as, for example, a membrane, a polystyrene or polycarbonate microwell, a polystyrene or polycarbonate rod or a glass support, followed by the addition of a quantity of plasma sample. The molecule is then “linked” or “captured”. The captured anti-FcεRI Ig is detected by the detection protein or detection antibody, which may be covalently linked to an enzyme, or may be detected by the addition of a secondary protein or antibody linked to an enzyme.

[0275] It is evident to the specialist that the essay formats Petition 870250100974, dated 04 / 11 / 2025, p. 62 / 216 57 / 172 described in this document are amenable to high-throughput formats, such as, for example, automated screening processes or a microarray format, as described in Mendoza et al., 1999. Furthermore, variations of the assay described above will be evident to subject matter experts, such as, for example, a competitive ELISA. LATERAL FLOW TESTS

[0276] The present invention offers a lateral flow assay for the detection and / or screening of an anti-FcεRI Ig in a plasma sample or a fraction thereof, the assay comprising a ligand and a lateral flow assay device.

[0277] Lateral flow assays, also known as “immunochromatographic strip tests”, operate on the same principles as enzyme-linked immunosorbent assays (ELISA). Essentially, these tests run a liquid sample along the surface of a membrane or filter paper with reactive molecules that show a positive or negative visual result depending on the presence of a specific analyte (e.g., an anti-FcεRI Ig).

[0278] A lateral flow assay device is a test system for the detection of analytes or components of interest in a sample, for example, to detect the presence of an anti-FcεRI Ig in a plasma sample or a fraction thereof. A lateral flow assay device is a device configured to receive a sample in a sample region and to allow the sample to move laterally, for example, by absorption, by capillary action from the sample region to a detection region. In certain examples, the lateral flow assay device further comprises one or more conjugation regions, wherein the lateral flow assay device is configured to allow lateral flow of a sample from a sample region to one or more conjugation regions before reaching a detection region. In related examples of a lateral flow assay device, a sample region is in Petition 870250100974, dated 04 / 11 / 2025, page 63 / 216 58 / 172 contact with a conjugation region and the conjugation region is in contact with one end of a detection region, so that the lateral flow assay device is configured to allow a sample to flow from the sample region to a conjugation region and finally to a detection region. In certain examples of the lateral flow assay device, the device further includes an absorbent region in contact with a detection region, so that the device is configured to allow the flow of a sample from a sample region to a detection region and finally to the absorbent region.

[0279] A side-mounted assay device typically has a matrix on which an optional sample region, an optional conjugation region, a detection region, and an optional absorbent region are mounted. The matrix (“backing card”) provides support for the actual assay pads and membranes but is not involved in the reaction or flow of the sample and analyte. Backing cards are, for example, made of polyvinyl chloride (PVC). Mounting the pads and membranes on the backing plate is usually done in a plastic compartment, although this is not required. The compartment may have more than one opening (“sample port”) over the sample pad for sample application. The control and test zones are visible (e.g., through an opening or window) to detect or measure the attached label. The compartment prevents the user from applying the sample anywhere except in the sample pad.The housing also serves to protect the strip from inadvertent splashes on the membrane. External labeling on the housing can also be used to indicate the position of the test and control lines and provide other information. Housings can be obtained as ready-to-use cassettes or custom-designed to fit the strip. Internal pins and bars can be used to hold the strip in place relative to the sampling port and viewing window. They keep the materials in fluid communication with each other. Petition 870250100974, dated 04 / 11 / 2025, page 64 / 216 59 / 172 while the test strip is working.

[0280] The “sample region”, if present, receives the sample after application and promotes uniform distribution of the sample in the detection region or in the conjugation region, if present. It may also influence the rate at which liquid enters the detection region, preventing flooding of the device. In addition, the sample block may also contain additional components, such as proteins, detergents, viscosity enhancers, and buffer salts, to process the sample (e.g., separation of sample components in the case of blood samples, removal of interferences, pH adjustment, viscosity increase, solubilization of components, and / or prevention of nonspecific binding between the conjugate and the analyte or other components or to the reaction membrane).

[0281] The “conjugated region” or “conjugation region,” if present, comprises a dry, mobilizable composition that includes the labeled antibody or labeled protein. When the sample flows into the conjugation region, the labeled antibody or labeled protein detaches from the material in the conjugation region and moves with the sample front to the detection region. If applicable, the conjugation region will also include the dry, mobilizable control conjugate.

[0282] In other examples, the lateral flow assay device does not include a separate conjugation region. In these examples, the sample is mixed with a composition that includes the labeled antibody or labeled protein disclosed herein in a separate container, prior to migration along the lateral flow assay device. These devices may be called lateral flow assay rods. For example, a plasma sample or fraction thereof from an individual may be brought into contact with the composition described in this document in a separate container to create a mixed solution, and then a lateral flow assay device with a detection region may be immersed in the solution. Petition 870250100974, dated 04 / 11 / 2025, page 65 / 216 60 / 172 so that it migrates along the detection region to the test and control zones.

[0283] The “detection region” is typically a membrane comprising a test zone and a control zone with irreversibly bound capture reagents, including an antibody or protein, an antibody against the labeled protein or labeled antibody, or a capture reagent such as streptavidin. Typically, the reaction membrane is made of a polymer such as nitrocellulose, polyvinylidene fluoride, nylon, or polyethersulfone. Nitrocellulose is an exemplary option for the reaction membrane. Nitrocellulose membranes bind proteins (such as antibodies or biotin-binding proteins) electrostatically through the interaction of the strong dipole of the nitrate esters with the strong dipoles of the peptide bonds within the protein.

[0284] The lateral flow assay device may also include an “absorbent region” or “absorption region.” The absorbent region is placed at the distal end of the detection region and holds the remaining sample. It conducts the fluid through the membrane and collects the processed liquid. In addition, it increases the total sample volume that can enter the detection region.

[0285] Suitable materials for a sample region, conjugation region, or detection region that may be included in a lateral flow assay device described in this document include, but are not limited to, organic or inorganic polymers and natural and synthetic polymers, including fiberglass, cellulose, nylon, crosslinked dextran, various chromatographic papers, and nitrocellulose. It should be considered that suitable materials will allow a sample to flow laterally, by capillary action, along the device described in this document. In some examples, the detection region is a nitrocellulose membrane. In some examples, a sample region and a conjugation region may be composed of the same material. In some examples, a Petition 870250100974, dated 04 / 11 / 2025, page 66 / 216 61 / 172 The lateral flow test device comprises a sample region in capillary contact with a detection region. Suitable commercially available materials are known to the expert. Commercially available materials may be used for a sample region, conjugation region and / or detection region that may be included in a lateral flow test device described in this document.

[0286] The lateral flow assay device may further include a sample filter membrane applied to the sample region. The sample filter membrane may be composed of any suitable material, including, but not limited to, a hydrophobic material capable of filtering cells (e.g., blood cells) from fluids. Suitable sample membranes will be apparent to the skilled person and may have, for example, a filter size of about 0.22 μm to about 10 μm.

[0287] In one example, a sample is applied to the sample region of a lateral flow assay device and the device is incubated. Incubation consists of allowing the device to remain at a temperature, for example, room temperature (e.g., about 20 °C to about 25 °C), so that the sample flows from the sample region to the detection region. In examples that also include a conjugation region, incubation involves allowing a lateral flow device to remain at a temperature, for example, room temperature (e.g., about 20 °C to about 25 °C), so that the sample flows from the sample region to the conjugation region followed by the detection region.

[0288] In one example, the lateral flow assay device is incubated after applying a sample to the sample region for about 2 minutes to about 20 minutes, about 2 minutes to about 15 minutes, or about 2 minutes to about 10 minutes. For example, the lateral flow assay device is incubated for about 10 minutes to about 15 minutes after applying a sample to the sample region. Petition 870250100974, dated 04 / 11 / 2025, page 67 / 216 62 / 172

[0289] In one example, the lateral flow test device may also include a control component immobilized in the control zone of the detection region. In one example, the detection region of a lateral flow test device is configured so that the sample passes through a test zone before the control zone. In one example, the test may also include inspection of the signal from a control line to confirm the valid operation of a lateral flow test device. The inspection may include visual confirmation of the signal on a control line.

[0290] In one example, the evaluation comprises a quantitative measurement of the molecules captured in a test zone and / or control zone. In another example, the evaluation may include a semi-quantitative or qualitative assessment of a test zone, for example, the detection of a signal above a predetermined threshold. The appropriate means for evaluating a test zone will depend on the signal generated by a test zone. For example, the detection may be optical, thermal, magnetic, or electrochemical. In another example, the evaluation may include the quantitative or qualitative measurement of the signal of, for example, a fluorescent dye or a colloidal metal. The evaluation may be done visually. The evaluation may be performed by a smartphone. In some examples, the evaluation may include the use of a portable fluorescence meter. Commercially available devices for measuring a signal from a lateral flow assay device are familiar to the expert. DETECTABLE MARKERS

[0291] As used in this document, a “detectable marker” is a molecular or atomic marker or label that generates or can be induced to generate an optical signal or other signal or product that can be detected visually or by means of a suitable detector. Detectable markers are well known in the art and include, for example, a radiolabel, an enzyme, a fluorescent marker, a luminescent marker, a bioluminescent marker, a marker Petition 870250100974, dated 04 / 11 / 2025, p. 68 / 216 63 / 172 magnetic, a prosthetic group, a contrast agent and an ultrasound agent.

[0292] Commonly used fluorescent markers include Alexa, cyanine, such as Cy5 and Cy5.5, and indocyanine, and fluorescein isothiocyanate (FITC), but are not limited to these. Fluorescent markers useful in the practice of the present invention may also include, without limitation, 1,5-IAEDANS; 1,8-ANS; 4-Methylumbelliferone; 5-carboxy-2,7-dichlorofluorescein; 5-Carboxyfluorescein (5-FAM); 5-Carboxinaptofluorescein (pH 10); 5-Carboxitetramethylrhodamine (5-TAMRA); 5-FAM (5-Carboxyfluorescein); 5-HAT (hydroxytryptamine); 5-Hydroxytryptamine (HAT); 5-ROX (carboxy-Xrhodamine); 5-TAMRA (5-Carboxitetramethylrhodamine); 6-Carboxyrodamine 6C; 6-CR 6G; 6-JOE; 7-Amino-4-methylcoumarin; 7-Aminoactinomycin D (7-AAD); 7-Hydroxy-4-methylcoumarin; 9-Amino-6-chloro-2-methoxycridine; ABQ; Acid fuchsin; ACMA (9-Amino-6-chloro-2-methoxycridine); Acridine Orange+DNA; Acridine Orange+RNA; Acridine Orange, both DNA & RNA; Acridine Red; Acridine yellow; Acriflavine; Acriflavine Feulgen SITSA;Aequorin (photoprotein); Alexa Fluor 350; Alexa Fluor 430; Alexa Fluor 488; Alexa Fluor 532; Alexa Fluor 546; Alexa Fluor 568; Alexa Fluor 594; Alexa Fluor 633; Alexa Fluor 647; Alexa Fluor 660; Alexa Fluor 680; Alizarin Complex; Alizarin Red; Allophycocyanin (APC); AMC, AMCA-S; AMCA (Aminomethylcoumarin); AMCA-X; Aminoactinomycin D; Aminocoumarin; Aminomethylcoumarin (AMCA); Anilin Blue; Anthrocyl stearate; APC (allophycocyanin); APC-Cy7; APTRA-BTC=Ratio Dye, Zn2+; APTS; Astrazon Brilliant Red 4G; Astrazon Orange R; Astrazon Red 6B; Astrazon Yellow 7 GLL; Atabrine; ATTO-TAG CBQCA; ATTO-TAG FQ; Auramine; Aurophosphine G; Aurophosphine; BAO 9 (Bisamminophenyloxadiazole); BCECF (high pH); BCECF (low pH); Berberine sulfate; Beta Lactamase; GFP with blue shift BFP (Y66H); Blue Fluorescent Protein; BFP / GFP FRET Bimane; Bisbenzamnide; Bisbenzimide (Hoechst); bis-BTC=Ratio Dye, Zn2+; Blancophor FFG; Blancophor SV; BOBO-1; BOBO-3; Bodipy 492 / 515; Bodipy; Petition 870250100974, dated 04 / 11 / 2025, p. 69 / 216 64 / 172 493 / 503; Bodipy 500 / 510; Bodipy 505 / 515; Bodipy 530 / 550; Bodipy 542 / 563; Bodipy 558 / 568; Bodipy 564 / 570; Bodipy 576 / 589; Bodipy 581 / 591; Bodipy 630 / 650-X; Bodipy 650 / 665-X; Bodipy 665 / 676; Bodipy Fl; Bodipy FL ATP; Bodipy Fl-Ceramide; Bodipy R6G SE; Bodipy TMR; Bodipy TMRX Conjugate; Bodipy TMR-X, SE; Bodipy TR; Bodipy TR ATP; Bodipy TR-X SE; BOPRO-1; BO-PRO-3; Brilliant Sulphoflavin FF; BTC-Ratio Ca2+ dye; BTC-5N-atio, Zn2+ dye; Calcein; Calcein Blue; Calcium Crimson; Calcium Green; Calcium Green-1 dye; Calcium Green-2 Ca2+ dye; Calcium Green-5N Ca2+ dye; Calcium Green-C18 Ca2+ dye; Calcium Orange; Calcofluor White; Carboxy-X-rhodamine (5-ROX); Cascade Blue; Cascade Yellow 399; Catecholamine; CCF2 (GeneBlazer); CFDA; CFP - Cyan Fluorescent Protein; CFP / YFP; FRET; Chlorophyll; Chromomycin A; Chromomycin A; CL-NERF (pH ratio dye); CMFDA; Coelenterazine; Coelenterazine cp (Ca2+ dye); Coelenterazine f; Coelenterazine fcp; Coelenterazine h; Coelenterazine hcp;Coelenterazine ip; Coelenterazine s.f; Coelenterazine O; Coumarin Phalloidin; C-ficocianina; CPM Methylcoumarin; CTC; CTC Formazan; Cy2; Cy3.1 8; Cy3.5; Cy3; Cy5.1 8; Cy5.5; Cy5; Cy7; GFP cyano; cyclic AMP fluorosensor (FiCRhR); CyQuant cell proliferation assay; Dabcyl; Dansyl; Dansyl Amine; Dansyl Cadaverine; Dansyl Chloride; Dansyl DHPE; Dansyl Fluoride; DAPI; Dapoxil; Dapoxil 2; Dapoxil 3; DCFDA; DCFH (Dichlorodihydrofluorescein Diacetate); DDAO; DHR (Dihydrorhodamine 123); Di-4ANEPPS; Di-8-ANEPPS (no proportion); DiA (4-Di-16-ASP); Dichlorodihydrofluorescein Diacetate (DCFH); Lipophilic Tracer DiD; DiD (DiIC18(5)); DIDS; Dihydrorhodamine 123 (DHR); DiI (DiIC18(3)); Dinitrophenol; DiO (DiOC18(3)); DiR; DiR (DiIC18(7)); DM-NERF (high pH); DNP; Dopamine; DsRed; Red fluorescent protein; DTAF; DY-630-NHS; DY-635-NHS; EBFP; ECFP; EGFP; ELF 97; Eosin; Erythrosine; Erythrosin ITC; Ethidium bromide; Ethidium homodimer-1 (EthD-1); Euchrysin; EukoLight; Europium (III) chloride; EYFP; FastBlue; FDA; Feulgen (Pararosaniline); FIF Petition 870250100974, dated 04 / 11 / 2025, page 70 / 216 65 / 172 (Formaldehyde-induced fluorescence); FITC; FITC antibody; Flazo Orange; Fluo-3; Fluo-4; Fluorescein (FITC); Fluorescein diacetate; Fluoro-Emerald; Fluoro-Gold (hydroxystilbamidine); Fluor-Ruby; FluorX; FM 1-43; FM 4-46; Fura Red (high pH); Fura Red / Fluo-3; Fura-2, high calcium; Fura-2, low calcium; Fura-2 / BCECF; Genacryl Brilliant Red B; Genacryl Brilliant Yellow 10GF; Genacryl Pink 3G; Genacryl Yellow 5GF; GeneBlazer (CCF2); GFP (S65T); Red-shifted GFP (rsGFP); Wild-type GFP, non-UV excited (wtGFP); Wild-type GFP, UV excited (wtGFP); GFPuv; Gloxalic Acid; Granulated Blue; Hematoporphyrin; Hoechst 33258; Hoechst 33342; Hoechst 34580; HPTS; Hydroxycoumarin; Hydroxystilbamidine (FluoroGold); Hydroxytryptamine; Indo-1, high calcium; Indo-1, low calcium; Indodicarbocyanine (DiD); Indotricarbocyanine (DiR); Intrawhite Cf; JC-1; JO-JO-1; JO-PRO-1; LaserPro; Laurodan; LDS 751 (DNA); LDS 751 (RNA);Leucophore PAF; Leucophore SF; Leucophore WS; Lissamine Rhodamine; Lissamine Rhodamine B; LIVE / DEAD Kit Animal cells, Calcine / Ethidium homodimer; LOLO1; LO-PRO-1; Lucifer Yellow; Lyso Tracker Blue; Lyso Tracker Blue-White; Lyso Tracker Green; Lyso Tracker Red; Lyso Tracker Yellow; LysoSensor Blue; LysoSensor Green; LysoSensor Yellow / Blue; Mag Green; Magdala Red (Phloxine B); Mag-Fura Red; Mag-Fura-2; Mag-Fura-5; Mag-Indo-1; Magnesium Green; Magnesium Orange; Malachite Green; Marina Blue; Maxilon Brilliant Flavin 10 GFF; Maxilon Brilliant Flavin 8 GFF; Merocyanin; Methoxycoumarin; Mitotracker Green FM; Mitotracker Orange; Mitotracker Red; Mithramycin; Monobromobiman; Monobromobiman (mBBr-GSH); Monochlorobiman; MPS (Methyl Green Pyronine Stilbene); NBD; NBD Amine; Nile Red; Nitrobenzoxadidole; Noradrenaline; Nuclear Fast Red; Nuclear Yellow; Nylosan Brilliant Iavin E8G; Oregon Green; Oregon Green 488-X; Oregon Green; Oregon Green 488; Oregon Green 500; Oregon Greene 514;Pacific Blue; Pararosaniline (Feulgen); PBFI; PE-Cy5; PECy7; PerCP; PerCP-Cy5.5; PE-TexasRed [Red 613]; Phloxin B (Red of; Petition 870250100974, dated 04 / 11 / 2025, p. 71 / 216 66 / 172 Magdala); Phorwite AR; Phorwite BKL; Phorwite Rev; Phorwite RPA; Phosphine 3R; PhotoResist; Phycoerythrin B [PE]; Phycoerythrin R [PE]; PKH26 (Sigma); PKH67; PMIA; Pontochrome Blue Black; POPO-1; POPO-3; PO-PRO-1; POPRO-3; Primulin; Procyon Yellow; Propidium Iodide (PI); PyMPO; Pyrene; Pyronine; Pyronine B; Pyrozal Brilliant Flavin 7GF; QSY 7; Quinacrine Mustard; Texas Red 613 [PE]; Resorufin; RH 414; Rhod-2; Rhodamine; Rhodamine 110; Rhodamine 123; Rhodamine 5 GLD; Rhodamine 6G; Rhodamine B; Rhodamine B 200; Rhodamine B extra; Rhodamine BB; Rhodamine BG; Rhodamine Green; Rhodamine phallicidin; Rhodamine paloidin; Rhodamine Red; Rhodamine WT; Rose Bengal; R-phycocyanin; R-phycoerythrin (PE); rsGFP; S65A; S65C; S65L; S65T; Sapphire GFP; SBFI; Serotonin; Sevron Brilliant Red 2B; Sevron Brilliant Red 4G; Sevron Brilliant Red B; Sevron Orange; Sevron Yellow L; sgBFP; sgBFP (super glow BFP); sgGFP; sgGFP (super glow GFP); SITS; SITS (Primuline);SITS (stilbene isothiosulfonic acid); Calcein SNAFL; SNAFL-1; SNAFL-2; SNARF calcein; SNARF1; Green Sodium; SpectrumAqua; SpectrumGreen; SpectrumOrange; Spectrum Red; SPQ (6methoxy-N-(3-sulfopropyl)quinolínio); Stilbene; Sulforodamine B pode C; Sulforodamine G Extra; SYTO 11; SYTO 12; SYTO 13; SYTO 14; SYTO 15; SYT; SYTO 17; SYTO 18; SYTO 20; SYTO 21; SYTO 22; SYTO 23; SYTO 24; SYTO 25; SYTO 40; SYTO 41; SYTO 42; SYTO 43; SYTO 44; SYTO 45; SYTO 59; SYTO 60; SYTO 61; SYTO 62; SYTO 63; SYTO 64; SYTO 80; SYTO 81; SYTO 82; SYTO 83; SYTO 84; SYTO 85; SYTOX Azul; SYTOX Verde; SYTOX Laranja; Tetracycline; Tetramethylrhodamine (TRITC); Texas Red; Conjugado Texas Red-X; Thiadicarbocyanine (DiSC3); Tiazina Vermelha R; Laranja thiazol; Thioflavin 5; Thioflavina S; Thioflavina TCN; Tiólito; Thiozole Orange; Tinopol CBS (Calcofluor White); TMR; TO-PRO-1; TO-PRO-3; TOPRO-5; TOTO-1; TOTO-3; TriColor (PE-Cy5); TRITC (TetramethylRodaminaIsoTioCianato); True Blue; TruRed; Ultralite; Uranina B; Uvitex SFC;GFP by weight; WW 781; X-Rhodamine; XRITC; Xylene Orange; Y66F; Y66H; Y66W; Petition 870250100974, dated 04 / 11 / 2025, p. 72 / 216 67 / 172 GFP yellow; YFP; YO-PRO-1; YO-PRO-3; YOYO-1; and YOYO-3.

[0293] In one example, a detectable marker is an enzyme. Examples of useful enzymes in the description include, but are not limited to, alkaline phosphatase and horseradish peroxidase. Alternatively or additionally, the enzyme may be, for example, luciferase. The enzyme may be linked to the antibody by conventional chemical methods or may be expressed along with the antibody as a fusion protein. In one example, the enzyme is horseradish peroxidase.

[0294] Useful radioisotopes as detectable tracers in the description are well known in the art and may include 3H, 11C, 18F, 35S, 64Cu, 67Ga, 68Ga, 99mTc, 111In, 123I, 1241, 125I and 131I. Effector cell analysis

[0295] The methods for determining the ratio of basophil and / or mast cell activation and / or basophil and / or mast cell degranulation from the revelation will be apparent to the qualified person and / or described in this document. For example, the ratio can be determined using ELISA, FLISA, or a lateral flow assay. Briefly, basophils and / or mast cells are incubated with the plasma sample or a fraction thereof for an appropriate period of time. Then, the cells are fixed and the ratio of basophil and / or mast cell activation and / or basophil and / or mast cell degranulation relative to the total proportion of basophils and / or mast cells exposed to the sample is analyzed by flow cytometry.

[0296] As used in this document, the term “ratio” in reference to basophil and / or mast cell activation should be understood as a measure of an activation marker.

[0297] As used in this document, the term “activation” should be understood as the stimulation of a cell (e.g., basophils and / or mast cells) by exposure to activation markers, such as a cellular or soluble ligand, which results in a change in the cell's morphology or behavior. Petition 870250100974, dated 04 / 11 / 2025, page 73 / 216 68 / 172

[0298] For example, after cell activation, the cell upregulates activation markers. In some instances, activation markers are selected from the group consisting of CD63, CD203c, CD107a and their combinations.

[0299] As used in this document, the term “degranulation” should be understood as the process by which cytoplasmic granules are released from cells (e.g., from mast cells and / or basophils).

[0300] In some examples, cell activation leads to degranulation. In other examples, cell activation does not lead to degranulation. For example, cell activation leads to increased cytokine production without degranulation.

[0301] In one example, basophil activation after exposure to a plasma sample or fraction thereof can be determined using basophil activation tests known in the art. For example, the test is a basophil activation test. The test uses activation markers to measure the ratio of activation and / or degranulation of basophils. For example, the activation marker is CD63. In another example, the activation marker is CD203c. CD63 and CD203c are useful markers for the cytometric flow quantification of activated basophils in vitro. In some examples, the basophils are activated human basophils.

[0302] In one example, the basophil activation ratio is determined using flow cytometry. In another example, the basophil activation ratio is determined by incubating basophils with a plasma sample or fraction thereof and quantifying the proportion of basophils expressing CD63 in the total basophil population using flow cytometry. In another example, the basophil activation ratio is determined by incubating basophils with a plasma sample or fraction thereof and quantifying the proportion of basophils expressing CD203c in the total basophil population using flow cytometry.

[0303] In one example, basophil activation is measured by the presence Petition 870250100974, dated 04 / 11 / 2025, page 74 / 216 69 / 172 of interleukin-3 (IL-3). In another example, basophil activation is measured by the absence of IL-3.

[0304] In another example, mast cell activation after exposure to a plasma sample or fraction thereof can be determined using commercially known mast cell activation assays. For example, the assay is a Hoxb8 mast cell activation test. The assay uses activation markers to measure the proportion of mast cells activated and / or degranulated. For example, the activation marker is CD107a. CD107a is a useful marker for flow cytometric quantification of activated mast cells in vitro. In some examples, the mast cells are Hoxb8 mast cells.

[0305] In one example, the proportion of mast cell activation is determined by incubating mast cells with a plasma sample or fraction thereof and quantifying the proportion of mast cells expressing CD107a in the total mast cell population using flow cytometry.

[0306] In summary, basophils or mast cells are incubated with the plasma sample or a fraction thereof. Detection of cell activation is performed by detecting the proportion of cells expressing an activation marker (e.g., CD63, CD203c, and / or CD107a). The activation proportion (i.e., the proportion of cells expressing the activation marker in the total cell population) is then quantified using flow cytometry.

[0307] For the specialist, based on the description in this document, it is evident that the methods for determining the activation and / or degranulation of basophils and / or mast cells are performed in vitro.

[0308] In one example, the method comprises determining a detectable amount of anti-FcεRI Ig in a plasma sample or fraction thereof by determining the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction thereof. In one example, a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if at least 5% of a basophil population Petition 870250100974, dated 04 / 11 / 2025, page 75 / 216 70 / 172 express CD63 after exposure to a plasma sample or plasma fraction. For example, the proportion of basophils expressing CD63 after exposure to a plasma sample or plasma fraction is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14%, or greater than 15% of the total population of basophils exposed to the plasma sample or plasma fraction.

[0309] In one example, the method comprises determining a detectable amount of anti-FcεRI Ig in a plasma sample or fraction thereof by determining the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction thereof. In one example, a detectable amount of anti-FcεRI Ig is present in the plasma sample or plasma fraction if at least 5% of a basophil population expresses CD203c after exposure to the plasma sample or plasma fraction. For example, the proportion of basophils expressing CD203c after exposure to the plasma sample or plasma fraction is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14%, or greater than 15% of the total population of basophils exposed to the plasma sample or plasma fraction.

[0310] In one example, the method comprises determining a detectable amount of anti-FcεRI Ig in a plasma sample or fraction thereof by determining the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction thereof. In one example, a detectable amount of anti-FcεRI Ig is present in the plasma sample or plasma fraction if at least 5% of a mast cell population expresses CD107a after exposure to the plasma sample or plasma fraction. For example, the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction thereof is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14%, or greater than 10%. Petition 870250100974, dated 04 / 11 / 2025, page 76 / 216 71 / 172 to 15% of the total mast cell population exposed to the plasma sample or a fraction thereof. METHODS FOR PREPARING REDUCED ANTI-FcsRI Ig PREPARATIONS

[0311] The present invention offers a method for preparing a reduced anti-FccRI Ig preparation from a plasma or a fraction thereof using a chromatography resin. For example, the description provides a method for preparing a reduced anti-FccRI Ig preparation from a plasma or a fraction thereof using an affinity chromatography resin. The affinity resin of the present invention comprises a ligand capable of specifically binding to an anti-FccRI Ig.

[0312] As used in this document, the terms “reduced” and “depleted” are used interchangeably and should be understood as an Ig preparation in which the amount of anti-FccRI Ig has been reduced relative to an Ig preparation in which the anti-FccRI Ig has not been reduced or depleted, and in a sufficient amount to prevent activation of the FccRI-mediated signaling pathway. As the qualified person may perceive from the description in this document, the anti-FccRI Ig need not be reduced or depleted by 100%, but only in an amount that prevents activation of the FccRI-mediated signaling pathway.

[0313] As used in this document, the terms “reduced basophil activation” and “reduced mast cell activation” should be understood as an Ig preparation in which the amount of anti-FccRI Ig is reduced, such that basophil or mast cell activation is reduced.As the specialist can appreciate, the reduction in basophil activation or the reduction in mast cell activation does not need to refer to a 100% decrease in activation, but only to a decrease relative to an Ig preparation in which anti-FccRI Ig has not been reduced or depleted. Petition 870250100974, dated 04 / 11 / 2025, p. 77 / 216 72 / 172

[0314] Suitable affinity chromatography resins will be apparent to the expert and / or described in this document. In one example, the resin comprises a ligand that includes an FcεRI or a fragment or epitope thereof. In another example, the resin comprises a ligand that includes an FcεRI antibody or a fragment thereof. The expert should be aware that FcεRI-based ligands are capable of specifically binding to all types of anti-FcεRI Ig (i.e., IgG and IgE). CONTINUOUS AFFINITY CHROMATOGRAPHY

[0315] In some examples, affinity chromatography is continuous affinity chromatography.

[0316] The term “continuous affinity chromatography” should be understood as a chromatographic method comprising one or more columns packed with resins of identical affinity, each column comprising one or more zones. A zone is a column, or a region of a column, that includes the resin in which one or more chromatographic steps can be performed. For example, a zone is selected from a group consisting of an equilibrium zone, a binding zone, a washing zone, an elution zone, a stripping zone, or a combination thereof.

[0317] Continuous affinity chromatography comprising more than one column involves connecting the columns in an arrangement that allows the columns to be operated in series and / or in parallel. In principle, IgG can be loaded onto a first column and / or subsequent columns while other columns (or other zones of a column) are undergoing equilibration, washing, elution, and / or regeneration simultaneously. Examples of continuous affinity chromatography will be apparent to the expert and / or described in this document.

[0318] Examples of columns that can be used to perform the continuous chromatography method will be apparent to the expert and / or described in this document. For example, the chromatography method Petition 870250100974, dated 04 / 11 / 2025, page 78 / 216 Continuous chromatography (73 / 172) can be performed with the Tricorn 5 / 100 (Cytiva). Alternatively, continuous chromatography can be performed using the BioSMB PD System (Sartorius). Simulated Moving Bed Chromatography (SMB)

[0319] In one example, continuous affinity chromatography is simulated moving bed (SMB) chromatography. The term “simulated moving bed chromatography” or “SMB chromatography” refers to a chromatography method first described in U.S. Patent 2,985,589. Examples of SMB chromatography setup and / or apparatus will be apparent to the qualified person and / or described in this document. The simulated moving bed concept involves the use of several smaller columns (instead of one large column) containing a solid absorbent (e.g., affinity resin) and performing one or more continuous chromatography steps (i.e., equilibration, binding, washing, elution, or removal) simultaneously on different columns in a continuous loop.

[0320] An example of an SMB chromatography setup has columns arranged in four sections with one or more columns per section. Two inlet streams (feed and eluent) and two outlet streams (extract and raffinate) are directed in alternating order into and out of the column ring. The inlet and outlet positions are switched at regular time intervals in the direction of the liquid flow, thus simulating the countercurrent movement of the columns. A feed (containing adsorbable components (extract)) is loaded into one or more columns of the SMB chromatography setup, and the extract binds to the resin within the columns. Meanwhile, the less adsorbed components (raffinate) in the feed pass through the column. The raffinate can be loaded into one or more subsequent columns or removed from the SMB chromatography system as waste. An eluent is loaded into the column to collect the extract.For example, eluate can be collected from an initial column while more feed is loaded into one or more subsequent columns. Petition 870250100974, dated 04 / 11 / 2025, page 79 / 216 74 / 172

[0321] Suitable washing and elution buffers with the characteristics of the present invention will be apparent to the skilled person and / or described in this document. In one example, the washing buffer is composed of 20 mM sodium dihydrogen phosphate, 145 mM sodium chloride and has a pH of 7.4.

[0322] The resin in SMB chromatography can be subjected to multiple cycles (e.g., 50 cycles) of resin equilibration, IgG loading, binding, elution, removal, sanitization, and / or regeneration per batch of plasma sample or fraction used. Multiple batch runs (e.g., 4 to 10 batches) can be performed using SMB chromatography. The total lifespan of the resin in SMB chromatography can be in the range of 200 to 500 cycles (if not more) before the resin becomes unusable. Resin regeneration is usually performed to allow for multiple uses of the resin. Countercurrent Periodic Chromatography (PCC)

[0323] In one example, continuous affinity chromatography is periodic countercurrent chromatography (PCC). Examples of PCC setup and / or apparatus will be apparent to the qualified person and / or described in this document. The PCC concept involves the use of multiple columns containing a solid absorbent (e.g., affinity resin) and the execution of the chromatography steps in parallel in a near-continuous manner. The buffers used in the ligation, washing, and / or elution steps flow countercurrently into the affinity resin.

[0324] An example of a PCC setup involves the use of two columns. In a first step, a sample is loaded onto a first column above the resin DBC, so that the unbound product (e.g., IgG) passes through the first column and is captured by the second column. In a second step, the first column is washed, eluted, cleaned, and / or rebalanced, regardless of whether the second column is loaded with another sample. In a third step, an additional sample is loaded onto the second column above the resin DBC, so that the Petition 870250100974, dated 04 / 11 / 2025, page 80 / 216 75 / 172 unbound product passes through the second column and is captured by the first column. In a fourth step, the second column is washed, eluted, cleaned and / or rebalanced, regardless of whether the first column is loaded with another sample. The process steps are continuously alternated between the two columns.

[0325] Another example of a PCC configuration involves the use of multiple columns. For example, a variation of the PCC configuration above might involve using multiple columns to capture the unbound product, which simulates the use of a large column. Continuous tangential countercurrent chromatography (CCTC)

[0326] In one example, continuous affinity chromatography is continuous countercurrent tangential chromatography (CCTC). Examples of CCTC setup and / or apparatus will be apparent to the qualified person and / or described in this document. The CCTC concept involves the use of affinity resin in a paste form, wherein the paste is continuously directed through several static mixers and hollow fiber membranes that separate the fluid phase from the resin. CCTC is typically performed at low pressures (e.g., <70kPa).

[0327] An example of a CCTC process involves binding, first wash, second wash, elution, stripping, and / or equilibration steps. The sample (e.g., plasma sample or fraction thereof) and affinity resin pass through static mixers and hollow fiber membranes in a binding step. Impurities are removed in the flow through the hollow fiber membranes in the washing step, while the resin-bound product (i.e., IgG) is retained by the membrane. The hollow fibers retain the resin and allow the product to flow in the elution step. The resins are stripped and / or equilibrated, and the process is repeated. Countercurrent continuous spiral chromatography (CCSC)

[0328] In one example, continuous affinity chromatography is the Petition 870250100974, dated 04 / 11 / 2025, page 81 / 216 76 / 172 Continuous countercurrent spiral chromatography (CCSC). Examples of CCSC configuration and / or apparatus will be apparent to the qualified person and / or described in this document. The CCSC concept involves the use of a compact rotating coil separation column mounted in a rotating centrifuge frame. There are two separation column designs currently available: the spiral disc assembly and the spiral tube support assembly.

[0329] An exemplary CCSC process involves a spiral separation column rotating around a central axis of the centrifuge while it rotates synchronously around its own axis (e.g., 1,000 to 1,200 rpm). A mobile phase can be passed through the centrifuge rotor without rotating seals, and a large amount of a stationary phase is retained while the two phases are mixed along the length of the column to produce a highly efficient solute separation. SHOCK ABSORBERS

[0330] The present invention provides an affinity chromatography method using buffers that allow efficient binding of Ig to the resin and its collection. In general, the plasma sample or fraction thereof is at a neutral pH (pH of approximately 7.4). The resin is equilibrated with an equilibration buffer and / or washed with a washing buffer with a buffering range covering the neutral pH. Suitable washing buffers include buffering agents with a dissociation constant (pKa) between 6.8 and 8.5 at 25 °C.

[0331] An exemplary buffering agent for equilibrium and / or washing buffers is sodium dihydrogen phosphate, wherein the phosphoric acid component of sodium dihydrogen phosphate has three dissociation constants (pKa: 2.16, 7.21, and 12.32). Phosphoric acid has a dissociation constant around the pH of an elution and / or removal buffer used in the continuous affinity chromatography method. However, phosphoric acid does not have a dissociation constant between the pH of the buffer of Petition 870250100974, dated 04 / 11 / 2025, page 82 / 216 77 / 172 equilibrium and / or washing (higher pH) and the elution and / or removal buffer (lower pH) used in the affinity chromatography method. This allows for a rapid changeover between the washing and elution steps, and the removal and equilibrium steps, providing more defined peaks and shorter chromatographic phases. An advantage of using these equilibrium and / or washing buffers is that smaller buffer volumes can be used, thus increasing the efficiency of the affinity chromatography method.

[0332] Other suitable buffering agents for equilibration and / or washing include imidazole (pKa: 7.0), Tris (pKa: 8.30), glycylglycine (pKa: 8.40), MOPS (pKa: 7.2), PIPES (pKa: 6.8), TES (pKa: 7.40), Bicin (pKa: 8.35), HEPES (pKa: 7.55), EPPS (pKa: 8.00), HEPPSO (pKa: 7.85), MOBS (pKa: 7.60), POPSO (pKa: 7.78), TAPSO (pKa: 7.61), Tricin (pKa: 8.05), TEA (pKa: 7.76). CHROMATOGRAPHY RESIN

[0333] The present invention offers a method for preparing a reduced preparation of Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) from a plasma sample or a fraction thereof using a continuous chromatography resin. In one example, the resin of the present invention comprises a ligand capable of specifically binding to an Fc epsilon I receptor immunoglobulin (Ig) (FcεRI).

[0334] In one example, the method also includes the use of an affinity chromatography resin to remove anti-A and anti-B antibodies. In one example, the method also includes the use of an affinity chromatography resin to remove anti-A antibodies. In one example, the method also includes the use of an affinity chromatography resin to remove anti-B antibodies.

[0335] Suitable chromatography resins will be apparent to the expert and / or described in document US2009 / 074749, incorporated herein by reference. In one example, the resin comprises a mixture of Petition 870250100974, dated 04 / 11 / 2025, page 83 / 216 78 / 172 supports whose matrices are grafted with oligosaccharide groups that have antigenic similarity to blood groups A and B. An exemplary resin is GlycosorbAbo® (Glycorex Transplantation AS). ADDITIONAL PURIFICATION STEPS

[0336] As will be understood by those skilled in the art, additional steps may be performed before or after the continuous chromatography step. In one example, the additional steps may be performed before the continuous chromatography step. In another example, the additional steps may be performed after the continuous chromatography step.

[0337] In one example, the method further comprises one or more steps selected from a group consisting of ethanol precipitation, octanoic acid fractionation, ion-exchange chromatography, viral inactivation, viral filtration, and ultrafiltration / diafiltration. Additional purification steps will be apparent to the expert and / or described in this document.

[0338] In one example, the method further comprises ethanol precipitation. For example, cold ethanol can be used to isolate and enrich the reduced anti-FcεRI Ig preparation by removing albumin and α and β globulins from the plasma sample or its fractions. For example, as described in WO2011 / 149472.

[0339] In one example, the method further comprises the fractionation of octanoic acid. Octanoic acid can be used to remove plasma lipids and proteins (except IgG). For example, as described in WO2011 / 131787.

[0340] In one example, the method further comprises ion-exchange chromatography. For example, anion-exchange chromatography can be used to remove IgA, residual IgM and other plasma components (except IgG).

[0341] The anion exchanger can be a resin-based anion exchanger, an anion exchange membrane adsorbent, or any other Petition 870250100974, dated 04 / 11 / 2025, page 84 / 216 79 / 172 Anion exchanger format with a positively charged substrate to capture negatively charged particles. In one example, the anion exchanger is an anion exchange membrane adsorbent. In another example, the anion exchanger is a resin-based anion exchanger. In yet another example, the anion exchanger is a monolithic anion exchanger.

[0342] In one example, the method further comprises anion exchange chromatography using a resin-based anion exchanger. For example, the anion exchange chromatography resin is a strong anion exchanger. In one example, the strong anion exchange resin comprises a matrix consisting of a poly(styrene-divinylbenzene) matrix. In one example, the strong anion exchanger comprises a quaternized polyethyleneimine functional group. Suitable resin-based anion exchangers will be apparent to the expert and include, for example, POROS™ HQ 50.

[0343] In one example, the anion exchange chromatography step is performed in flow mode. In another example, the anion exchange chromatography step is performed in bind-and-elute mode.

[0344] In one example, the anion exchange chromatography step comprises a buffer selected from the group consisting of sodium citrate, 2-(N-morpholino)ethanesulfonic acid (MES) buffer, sodium dihydrogen phosphate, Bis-Tris phosphate, L-histidine, and combinations thereof. In one example, the anion exchange chromatography step comprises a buffer comprising MES buffer. In another example, the anion exchange chromatography step comprises phosphate buffer.

[0345] In one example, the method also includes viral inactivation. For example, viral inactivation can be achieved by adjusting the solution to a low pH. A low pH can be between 2 and 4. In one example, low pH viral inactivation is performed in the presence of caprylate. In another example, viral inactivation can be achieved by contact of the sample with... Petition 870250100974, dated 04 / 11 / 2025, page 85 / 216 80 / 172 plasma or a fraction thereof, or of the reduced anti-FcεRI Ig preparation or of the pharmaceutical composition comprising the reduced anti-FcεRI Ig preparation with n-Octyl-εD-Glucopyranoside (OG), thus forming an OG-IgG mixture. In another example, viral inactivation at low pH is carried out in the presence of N,N-Dimethylmyristylamine N-oxide (TDAO).

[0346] In another example, viral inactivation can be effected by exposing the protein mixture, plasma or plasma fraction, a protein-reduced preparation or composition (e.g., a plasma protein-reduced preparation, e.g., an IgG-reduced preparation) to a solvent-detergent inactivation step. Suitable solvent-detergent treatments would be apparent to a qualified person and include, for example, environmentally friendly detergents. Some examples of environmentally friendly detergents suitable for use in the present invention and, in particular, for use in the inactivation of lipid-enveloped viruses include N,N-Dimethylmyristylamine N-oxide (TDAO), polysorbate 80 (PS80), polyoxyethylene (10) isooctylcyclohexyl ether (TRITON® X-100-reduced) and a nonionic surfactant prepared from glucose and alcohol (e.g., Simulsol™ formulations). In one example, the detergent is N,N-Dimethylmyristylamine N-oxide (TDAO).In one example, the detergent is polysorbate 80. In another example, the detergent is polyoxyethylene (10) isooctylcyclohexyl ether (TRITON® X-100-reduced). In yet another example, the detergent is a nonionic surfactant prepared from glucose and alcohol.

[0347] In one example, the method further comprises viral filtration. For example, viral filtration membranes with pores of 1 to 20 nm can be used to remove microbes and viruses from a solution, eluate, or pharmaceutical composition. An example of a nanofilter is Planova 20 (Planova), which includes Planova S20N (Asahi), Virosart HC (Sartorius), and Planova 20N (Asahi).

[0348] In one example, the method also includes Petition 870250100974, dated 04 / 11 / 2025, page 86 / 216 81 / 172 Ultrafiltration / Diafiltration. An exemplary ultrafiltration / diafiltration membrane is the Pellicon 2 Cassettes (Millipore) or the Polyethersulfone or Hydrosart cassettes (Sartorius). Analysis of the reduced preparation of anti-FcsRI Ig

[0349] In one example, the activity of the reduced antiFcsRI Ig preparation is evaluated. The methods for determining the yield, purity, and distribution of the IgG subclass will be apparent to the expert and / or described in this document.

[0350] In one example, purity is determined by SDS-PAGE and MALDI-TOF-MS peptide fingerprint analysis. Briefly, purified plasma protein products or pharmaceutical compositions described in this document are loaded onto a suitable SDS-PAGE gel (e.g., 8-16% TRIS-glycine), along with a protein size marker and a positive control for the protein of interest (e.g., IgG, such as IVIG) under reduced and non-reduced conditions. Proteins are separated based on size, and bands of proteins of interest are isolated, processed, and analyzed by MALDI-TOF-MS.

[0351] In another example, impurities in the reduced anti-FcsRI Ig preparation or in the pharmaceutical composition described herein are measured in an enzyme-linked immunosorbent assay (ELISA) using antibodies specific for impurities (e.g., IgA). For example, the ELISA is performed using commercially available methods.

[0352] In one example, the purity, yield and / or distribution of IgG subclasses are determined by nephelometry.

[0353] In one example, the reduced anti-FcsRI Ig preparation comprises a purity of more than 95% Ig. For example, the reduced anti-FcsRI Ig preparation comprises a purity of more than 96% Ig. In another example, the reduced anti-FcsRI Ig preparation comprises a purity of more than 97% Ig. In yet another example, the reduced preparation of Petition 870250100974, dated 04 / 11 / 2025, page 87 / 216 82 / 172 Anti-FcεRI Ig comprises a purity of more than 98% Ig. In another example, the reduced anti-FcεRI Ig preparation comprises a purity of more than 99% Ig. Plasma Stability and Plasma Fraction

[0354] The stability of the plasma sample or fraction thereof for loading onto a chromatographic resin described herein can be determined by evaluating the procoagulant activity, proteolytic activity, and particle size of the plasma sample or fraction thereof. The methods for evaluating procoagulant activity, proteolytic activity, and particle size will be apparent to an experienced person and / or described in this document. Briefly, the plasma or plasma fraction is frozen / thawed in one or more cycles, stored between 2 °C and 32 °C (e.g., 2 °C, 10 °C, 18 °C, 21 °C, 28 °C, or 32 °C) for 24 or up to 48 hours, and analyzed using one or more of the methods described below. In one example, the plasma sample or fraction thereof is thawed in one or more cycles at a temperature of 32 °C, stored for 24 or up to 48 hours, and analyzed using one or more of the methods described below.In another example, the plasma sample or fraction thereof is thawed in one or more cycles at a temperature of 32 °C, stored for 24 or up to 48 hours, and analyzed using one or more of the methods described below, and then cooled and stored at a temperature of 21 °C. In one example, the plasma sample or fraction thereof is thawed at a temperature of 32 °C and at a temperature of 21 °C before continuous chromatography.

[0355] In one example, procoagulant activity in a plasma sample or fraction thereof can be determined using an in vitro coagulation assay, for example, the activated partial thromboplastin time (NaPTT) assay. The NaPTT assay measures the rate at which one or more coagulation factors (e.g., fibrinogen, prothrombin, proaccelerin, anti-hemophilic factor, Stuart-Prower factor, anti-thromboplastin) are produced. Petition 870250100974, dated 04 / 11 / 2025, page 88 / 216 83 / 172 plasma and Hegeman factor) are activated or formed in a plasma sample or fraction thereof when coagulation activators (e.g., silica, kaolin, ellagic acid) are added to the assay.

[0356] In one example, proteolytic activity in a plasma sample or fraction thereof can be assessed by measuring the activity of thrombin, general serine proteases, kallikrein, plasmin and FXa, for example, using commercially available kits such as the thrombin activity assay kit (S-2238), the general serine protease assay kit (S-2288), the kallikrein activity assay kit (S-2302), the plasmin activity assay kit (S-2251) and the FXa activity kit (S-2765).

[0357] In one example, the size of any particle in the plasma sample or fraction thereof is evaluated by microflow imaging (MFI) and the polydispersity index is calculated. The calculation of the polydispersity index will be evident to the specialist. PHARMACEUTICAL COMPOSITIONS

[0358] The anti-FcεRI reduced Ig plasma preparations and the anti-FcεRI reduced Ig IgG preparations described are useful for formulations in a pharmaceutical composition for parenteral administration, such as intravenous or subcutaneous administration, for therapeutic and prophylactic treatment.

[0359] A pharmaceutical composition of the present invention, according to a preferred embodiment, comprises a reduced anti-FcεRI Ig preparation or a reduced anti-FcεRI Ig IgG plasma preparation.

[0360] Compositions for administration generally comprise a solution of the reduced anti-FcεRI Ig preparation or the reduced anti-FcεRI Ig IgG preparation of the description dissolved in a pharmaceutically acceptable vehicle, such as an aqueous vehicle. Various aqueous carriers may be used, for example, buffered saline solution and the like. The compositions may contain pharmaceutically acceptable vehicles as necessary to approximate physiological conditions, such as Petition 870250100974, dated 04 / 11 / 2025, page 89 / 216 84 / 172 as pH adjusting and buffering agents, toxicity adjusting agents and the like, for example, sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like.

[0361] The concentration of Ig in the pharmaceutical composition of the present invention in these formulations may vary widely and will be selected primarily based on fluid volumes, viscosities, body weight and the like, according to the specific mode of administration selected and the patient's needs. The vehicles may contain small amounts of additives that increase isotonicity and chemical stability, for example, buffers and preservatives. For example, the pharmaceutical composition comprises proline as a stabilizing agent.

[0362] Suitable pharmaceutical compositions, according to the description, generally include an amount of the reduced anti-FcεRI Ig preparation of the present invention mixed with an acceptable pharmaceutical vehicle, such as a sterile aqueous solution, to provide a variety of final concentrations, depending on the intended use. Preparation techniques are generally known in the art, as exemplified in Remington's Pharmaceutical Sciences, 16th Ed. Mack Publishing Company, 1980.

[0363] For example, the total Ig concentration of the pharmaceutical composition is 1 to 5% w / v, 5 to 15% w / v, or 8 to 12% w / v. For example, the total Ig concentration of the pharmaceutical composition is 1%, or 2%, or 3%, or 4%, or 5%, or 6%, or 7%, or 8%, or 9%, or 10%, or 11%, or 12%, or 13%, or 14%, or 15% w / v. For intravenous use, 1% w / v (i.e., 10g Ig / L) can be used. For intravenous use, 10% w / v (i.e., 100g Ig / L) can be used.

[0364] For subcutaneous administration, a higher concentration may be used. For example, 15 to 35% w / v, or 20 to 30% w / v. In one example, the total Ig concentration of the pharmaceutical composition is 16%, or 17%, or 18%, or 19%, or 20%, or 21%, or 22%, or 23%, or 24%, or Petition 870250100974, dated 04 / 11 / 2025, pp. 90 / 216 85 / 172 25%, or 26% p / v. Reduced Ig Preparations of Anti-FcsRI Ig

[0365] The present invention provides a reduced preparation of Fc epsilon I receptor immunoglobulin (Ig), comprising polyclonal IgG.

[0366] The present invention also provides a reduced immunoglobulin (Ig) anti-Fc epsilon I receptor (FceRI) preparation, comprising polyclonal IgG.

[0367] In one example, polyclonal IgG is present in an amount of 5 to 25% (w / v). In one example, polyclonal IgG is present in an amount of 6 to 15% (w / v). In one example, polyclonal IgG is present in an amount of approximately 8 to 12% (w / v). In one example, polyclonal IgG is present in an amount of approximately 10% (w / v).

[0368] The final protein concentration will depend on several factors, such as route of administration, type of condition to be treated, etc. A person skilled in the art will be able to determine the ideal protein concentration for the intended application.

[0369] For example, for intravenous infusion, polyclonal IgG is present in an amount of about 15 to 20% (w / v). In one example, polyclonal IgG is present in an amount of about 8 to 12% (w / v). In another example, polyclonal IgG is present in an amount of about 20% (w / v).

[0370] For subcutaneous administration, a higher dosage may be chosen, for example, approximately 15 to 20% (w / v). In one example, polyclonal IgG is present in an amount of approximately 20% (w / v).

[0371] Immunoglobulins can be isolated from human or animal blood or produced by other means, for example, by recombinant DNA technology or hybridoma technology. In one example, immunoglobulin is obtained from blood plasma, usually from a plasma pool. Petition 870250100974, dated 04 / 11 / 2025, page 91 / 216 86 / 172 blood samples from multiple donors. To obtain the immunoglobulins from the plasma, the plasma is subjected to alcohol fractionation, which can be combined with other purification techniques such as chromatography, adsorption, or precipitation, as described in this document. However, other processes can also be used.

[0372] The pharmaceutical compositions described are formulated by methods known in the art. In the case of an IgG solution, the pH of the final preparation is adjusted to a relatively high, but acidic pH, i.e., in the range of about pH 4.2 to 5.4. This pH range has been found to be particularly useful for improving the storage characteristics of polyclonal IgG preparations. In one example, the pH is about 4.6 to 5.0. In another example, the pH is 4.8.

[0373] In other examples, the pharmaceutical composition further comprises a stabilizer. In one example, the stabilizer is composed of more than one amino acid. For example, the amino acids are selected from the group consisting of nonpolar and basic amino acids. In some examples, the amino acid is selected from the group consisting of histidine, arginine, lysine, ornithine, isoleucine, valine, methionine, glycine, and proline.

[0374] In one example, the stabilizer is proline. For example, the proline is L-proline. The amount of proline in the pharmaceutical composition varies from about 10 to about 2,000 mmol / l. In some examples, the amount of proline in the pharmaceutical composition varies from about 50 to about 1,000 mmol / l. In other examples, the amount of proline in the pharmaceutical composition varies from approximately 100 to 500 mmol / l.

[0375] In one example, the amount of L-proline in the pharmaceutical composition varies from about 200 mmol / L to 300 mmol / L. For example, the amount of L-proline in the preparation varies from 225 mmol / L to 275 mmol / L. In one example, the amount of L-proline in the pharmaceutical composition varies from about 240 mmol / L to 260 mmol / L. For example, the amount of L-proline in the pharmaceutical composition varies from about 250 mmol / L. Petition 870250100974, dated 04 / 11 / 2025, p. 92 / 216 87 / 172

[0376] In other examples, the amount of proline in the pharmaceutical composition is about 250 mmol / l.

[0377] In one example, the final proline concentration is between 200 mM and 400 mM. In another example, the final proline concentration is 250 mM.

[0378] In one example, proline is L-proline. In another example, proline is a proline equivalent (e.g., proline analogs).

[0379] In other examples, the stabilizer is present in the pharmaceutical composition at a concentration of more than 200 mM. In some examples, the stabilizer is present in the pharmaceutical composition at a concentration between 200 mM and 400 mM. In other examples, the stabilizer is present in the pharmaceutical composition at a concentration between 200 mM and 300 mM. In other examples, the stabilizer is present in the pharmaceutical composition at a concentration of 250 mM.

[0380] In one example, the pharmaceutical composition comprises a pH between 4 and 5.5. For example, the pharmaceutical composition comprises a pH between 4.5 and 5.0. In one example, the pharmaceutical composition comprises a pH between 4.6 and 5.0. For example, the pharmaceutical composition comprises a pH of 4.6. In one example, the pharmaceutical composition, the Ig preparation, or the reduced anti-FcεRI Ig preparation has a pH of 4.7. In another example, the pharmaceutical composition comprises a pH of 4.8. In another example, the pharmaceutical composition comprises a pH of 4.9. In one example, the pharmaceutical composition comprises a pH of 5.0.

[0381] In one example, the pharmaceutical composition comprises 100 mg / mL of total human plasma protein. In one example, the pharmaceutical composition comprises 20 g / 100 mL of total human plasma protein.

[0382] In one example, the pharmaceutical composition comprises a purity of more than 95% of immunoglobulin G (IgG). For example, the pharmaceutical composition comprises a purity of more than 96% of Petition 870250100974, dated 04 / 11 / 2025, page 93 / 216 88 / 172 immunoglobulin G (IgG). In another example, the pharmaceutical composition comprises a purity of more than 97% immunoglobulin G (IgG). In another example, the pharmaceutical composition comprises a purity of more than 98% immunoglobulin G (IgG). In another example, the pharmaceutical composition comprises a purity of more than 99% immunoglobulin G (IgG).

[0383] In one example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG1 subclass distribution of more than 60%. For example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG1 subclass distribution of more than 65%.

[0384] In one example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG2 subclass distribution of less than 30%. For example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG2 subclass distribution of less than 28%.

[0385] In one example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG3 subclass distribution of less than 5%. For example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG3 subclass distribution of less than 4%.

[0386] In one example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG4 subclass distribution of less than 5%. For example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG4 subclass distribution of less than 3%.

[0387] In one example, the pharmaceutical composition or reduced anti-FcεRI Ig preparation comprises an IgG subclass distribution that is similar to that of normal human plasma, for example, 69% IgG1, 26% IgG2, 3% IgG3 and 2% IgG4. Petition 870250100974, dated 04 / 11 / 2025, p. 94 / 216 89 / 172

[0388] In one example, the pharmaceutical composition comprises a nominal osmolality between about 300 mOsm / kg and 400 mOsm / kg. In one example, the pharmaceutical composition comprises a nominal osmolality of 380 mOsm / kg. For example, the pharmaceutical composition comprises a nominal osmolality between about 300 mOsm / kg and 350 mOsm / kg. In one example, the pharmaceutical composition comprises a nominal osmolality of 320 mOsm / kg.

[0389] In one example, the pharmaceutical composition comprises a sodium content of < 1 mmol / L.

[0390] In one example, the pharmaceutical composition comprises an IgA content of < 0.05 mg / mL. For example, the pharmaceutical composition comprises an IgA content < 0.04 mg / mL or < 0.03 mg / mL. In one example, the pharmaceutical composition comprises an IgA content of < 0.025 mg / mL. In one example, the pharmaceutical composition comprises an IgA content of < 0.01 mg / mL. For example, the pharmaceutical composition comprises an IgA content of < 0.009 mg / mL.

[0391] In one example, the pharmaceutical composition comprises an IgA content < 0.1 mg / g of IgG.

[0392] In one example, the pharmaceutical composition comprises an IgA content of <0.09 mg / g of IgG.

[0393] In one example, the pharmaceutical composition comprises an IgM content of < 10 mg / L. For example, an IgM content of < 10 mg / L, < 9 mg / L, < 8 mg / L, < 7 mg / L, < 6 mg / L, < 5 mg / L, < 4 mg / L, < 3 mg / L, < 2 mg / L. In one example, the pharmaceutical composition comprises an IgM content of < 2 mg / L. In one example, the pharmaceutical composition comprises an IgM content < 1 mg / L. In one example, the pharmaceutical composition comprises an IgM content < 0.5 mg / L. For example, the pharmaceutical composition comprises an IgM content of < 0.17 mg / L.

[0394] In one example, the pharmaceutical composition comprises an IgM content of < 2 μg / g IgG. Petition 870250100974, dated 04 / 11 / 2025, page 95 / 216 90 / 172

[0395] In one example, the pharmaceutical composition comprises an IgM content of < 1.9 μg / g of IgG.

[0396] In one example, the pharmaceutical composition comprises an albumin content < 0.50 mg / mL. For example, the pharmaceutical composition comprises an albumin content < 0.40 mg / mL. In one example, the pharmaceutical composition or reduced Ig preparation of anti-FcεRI Ig comprises an albumin content of < 0.30 mg / mL. In one example, the pharmaceutical composition comprises an albumin content < 0.20 mg / mL. In one example, the pharmaceutical composition comprises an albumin content < 0.10 mg / mL. For example, the pharmaceutical composition contains an albumin content < 0.09 mg / mL. In one example, the pharmaceutical composition comprises an albumin content < 0.08 mg / mL. In one example, the pharmaceutical composition comprises an albumin content < 0.07 mg / mL.

[0397] In one example, the pharmaceutical composition comprises an albumin content of < 1 mg / g of IgG. In one example, the pharmaceutical composition comprises an albumin content < 0.80 mg / g of IgG.

[0398] In one example, the pharmaceutical composition comprises a prekallikrein activator (PKA) level of < 35 IU / mL. In one example, the pharmaceutical composition comprises a prekallikrein activator (PKA) level of < 30 IU / mL. In one example, the pharmaceutical composition comprises a prekallikrein activator (PKA) level of < 50 IU / mL. In one example, the pharmaceutical composition comprises a prekallikrein activator (PKA) level of < 20 IU / mL. For example, the pharmaceutical composition comprises a prekallikrein activator (PKA) level of < 15 IU / mL. In one example, the pharmaceutical composition comprises a prekallikrein activator (PKA) level of < 10 IU / mL.

[0399] In one example, the reduced anti-FcεRI Ig preparation comprises polyclonal IgG in an amount of 10% (w / v), proline at a concentration of 250 mM and a pH of 4.8. Petition 870250100974, dated 04 / 11 / 2025, p. 96 / 216 91 / 172

[0400] In one example, the reduced anti-FcεRI Ig preparation comprises polyclonal IgG in an amount of 20% (w / v), proline at a concentration of 250 mM, PS80 in an amount of 20 pg / mL and a pH of 4.8.

[0401] Exemplary methods for purifying Ig processes are described in document WO2015 / 000886, and exemplary IgG products are described in document WO2016 / 087569, both of which are incorporated herein by reference.

[0402] The present invention also offers a combined IgG preparation, wherein the combined IgG preparation comprises a detectable amount of anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI). To the skilled, from the description in this document, it will be evident that the combined IgG preparation with a detectable amount of anti-FcεRI Ig has not been subjected to any method of the present invention. Thus, the present invention also offers a method for detecting anti-FcεRI Ig in a combined IgG preparation.

[0403] In one example, the combined IgG preparation comprises other isotypes, such as IgA and IgM. In one example, the combined IgG preparation comprises IgA. In one example, the combined IgG preparation comprises other IgM isotypes. HOW TO USE

[0404] As discussed herein, the present invention provides a method of treating, preventing and / or delaying the progression of a condition related to a primary or secondary immunodeficiency, an inflammatory disease, an autoimmune disease or an acute infection in an individual, comprising administering a reduced anti-FcεRI Ig preparation, a reduced anti-FcεRI Ig preparation or a pharmaceutical formulation to the individual.

[0405] The present invention also provides a reduced anti-FcεRI IgG preparation or a reduced anti-FcεRI Ig IgG preparation. Petition 870250100974, dated 04 / 11 / 2025, page 97 / 216 92 / 172 or a pharmaceutical composition described in this document for use in treating, preventing and / or delaying the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual.

[0406] The present invention further provides a reduced anti-FcεRI Ig IgG preparation or a reduced IgFcεRI Ig IgG preparation or a pharmaceutical composition described herein for the manufacture of a medicament to treat, prevent and / or delay the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease and / or an acute infection in an individual.

[0407] In one example, the condition is selected from a group consisting of primary immunodeficiency disease (PI), chronic inflammatory demyelinating polyneuropathy (CIDP), chronic immune thrombocytopenic purpura (ITP), and combinations thereof.

[0408] In one example, the condition is primary immunodeficiency disease (PI).

[0409] In one example, the condition is chronic inflammatory demyelinating polyneuropathy (CIDP).

[0410] In one example, the condition is chronic immune thrombocytopenic purpura (ITP).

[0411] In another example, the condition is selected from the group consisting of congenital agammaglobulinemia and hypogammaglobulinemia, common variable immunodeficiency, severe combined immunodeficiency, allogeneic bone marrow transplantation, pediatric HIV chronic lymphocytic leukemia, kidney transplantation with a recipient with a high antibody index or with an ABO incompatible donor, chronic fatigue syndrome, Clostridium difficile colitis, Graves' ophthalmopathy, muscular dystrophy, inclusion body myositis, Lambert-Eaton syndrome, lupus erythematosus, multifocal motor neuropathy, myasthenia gravis, alloimmune thrombocytopenia Petition 870250100974, dated 04 / 11 / 2025, pp. 98 / 216 93 / 172 neonatal, Parvovirus B19 infection, pemphigus, post-transfusion purpura, renal transplant rejection, spontaneous abortion, stiff-person syndrome, opsoclonus, myoclonus, severe sepsis and septic shock in critically ill adults, toxic epidermal necrolysis, chronic lymphocytic leukemia, multiple myeloma, X-linked agammaglobulinemia, hypogammaglobulinemia, RRMS, IgG subclass deficiencies with recurrent infections, and combinations thereof.

[0412] In other examples, treatment also includes replacement therapy in myeloma or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections.

[0413] In other examples, the condition is selected from a group consisting of autoimmune diseases and certain neurological diseases, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), antiphospholipid syndrome, immune thrombocytopenia (ITP), Kawasaki disease, Guillain-Barré syndrome (GBS), multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), myasthenia gravis (MG), skin blistering diseases, scleroderma, dermatomyositis, polymyositis, Alzheimer's disease, Parkinson's disease, Down syndrome-related Alzheimer's disease, cerebral amyloid angiopathy, dementia with Lewy bodies, frontotemporal lobar degeneration, vascular dementia, cell and organ transplantation, and combinations thereof.

[0414] In some examples, the pharmaceutical composition is contained in a vial, a pre-filled syringe, or an autoinjector device.

[0415] The present invention also provides a pre-filled syringe comprising the pharmaceutical composition described in this document.

[0416] The present invention also provides an autoinjector device comprising the pharmaceutical composition described in this document.

[0417] In one example, the composition described is administered subcutaneously to the individual who needs it. In another example, the Petition 870250100974, dated 04 / 11 / 2025, page 99 / 216 94 / 172 composition of the description is administered intravenously to the individual who needs it.

[0418] In one example, the composition of the description is self-managed.

[0419] In one example, the composition described is self-administered subcutaneously.

[0420] In one example, the composition of the description is provided in a pre-filled syringe.

[0421] In one example, the composition described is self-administered subcutaneously, using a pre-filled syringe.

[0422] In an example of any method described in this document, the individual is a mammal, for example, a primate, such as a human being. KITS

[0423] Another example of the description provides kits containing an FcεRI or fragment or epitope thereof for use in any method described in this document (e.g., detection of an anti-FcεRI Ig in a plasma sample or fraction thereof).

[0424] In one instance, the panel or kit, as described in this document, is for ex vivo analysis. In one instance, the kit is suitable for use with a whole blood sample, a plasma sample, or a fraction thereof.

[0425] Reagents for specific types of assays may also be provided in the kits. In one example, the kits include a device, such as a lateral flow assay device, an analytical rotor, or an electrochemical, optical, or optoelectronic sensor, or a plate (e.g., a plate suitable for an ELISA assay). In examples where the kit comprises a lateral flow assay device, a ligand (e.g., FcεRI or fragment or epitope thereof) may be contained in the kit, separate from the device, or may be included in the device itself, for example, it may be dried in a conjugate region within the device.

[0426] In addition, the kit includes several diluents and buffers, combined Petition 870250100974, dated 04 / 11 / 2025, pages 100 / 216 95 / 172 labeled or other agents for carrying out the methods described above and other signal-generating reagents, such as enzyme substrates, cofactors, and chromogens. Other components of the kit can be easily determined by a person skilled in the art. These components may include coating reagents, indicator charts for colorimetric comparisons, disposable gloves, decontamination instructions, applicator sticks or containers, a sample preparation cup, etc. In one example, a kit comprises buffers or other reagents suitable for constituting a reaction medium in which the composition disclosed herein is brought into contact with the sample.

[0427] In one example, the kit further comprises an instruction or information leaflet with instructions for the detection and / or screening of an anti-FcεRI Ig in a plasma sample or fraction thereof. For example, in certain examples, the kit comprises an instruction indicating how to use the kit to detect an anti-FcεRI Ig, or to select and / or identify plasma samples suitable for administration to an individual, or to identify suitable and / or unsuitable individuals for plasma donation for the production of an Ig preparation. In one example, the kit comprises an instruction indicating how to prepare a sample. In one example, the kit provides instructions for contacting the sample with a ligand disclosed in this document (i.e., FcεRI or a fragment or epitope thereof) in any order before analyzing the sample to check for the presence of an anti-FcεRI Ig.The kit can also provide instructions for optimizing buffers, optimizing the ratios of various components, optimizing sample dilution, and optimizing the order of mixing and application steps (e.g., mixing all components before application, mixing only some components and applying others separately).

[0428] The invention is disclosed in more detail in the numbered paragraphs below: Petition 870250100974, dated 04 / 11 / 2025, pp. 101 / 216 96 / 172

[0429] 1. A method for detecting an Fc epsilon I anti-receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, the method comprising:

[0430] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0431] (ii) detect the complex, the presence of the complex being indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0432] 2. A screening method of a plasma sample or a fraction thereof for an anti-Fc epsilon I receptor immunoglobulin (Ig), the method comprises:

[0433] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0434] (ii) detect the complex, the presence of the complex being indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0435] 3. A method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, the method includes:

[0436] (i) bringing the sample into contact with a ligand that binds to anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0437] (ii) detect the complex, the presence of the complex being indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, the presence of anti-FcεRI Ig in the sample or plasma fraction indicating that the sample or plasma fraction is not suitable for administration to the individual.

[0438] 4. A method for screening a plasma sample or a fraction thereof to determine its suitability for administration to an individual, the method comprises:

[0439] (i) bring the sample into contact with a ligand that binds to an Fc epsilon I receptor (FcεRI) immunoglobulin (Ig) in the sample to form a complex; and Petition 870250100974, dated 04 / 11 / 2025, page 102 / 216 97 / 172

[0440] (ii) detect the complex, the presence of the complex being indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, the presence of anti-FcεRI Ig in the sample or plasma fraction indicating that the sample or plasma fraction is not suitable for administration to the individual.

[0441] 5. A method for identifying a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0442] (i) contact of the sample with a ligand that binds to the anti-Fc epsilon Receptor I (FcεRI) in the sample to form a complex; and

[0443] (ii) detect the complex, the presence of the complex being indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, the presence of anti-FcεRI Ig in the sample or plasma fraction indicating that the sample or plasma fraction is not suitable for use in the production of an Ig preparation for administration to an individual.

[0444] 6. A method for screening a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0445] (i) contact of the sample with a ligand that binds to an Fc epsilon I antireceptor Ig (FcεRI) in the sample to form a complex; and

[0446] (ii) detecting the complex, and the presence of the complex is indicative of the presence of anti-FcεRI Ig in the sample or plasma fraction, and the presence of anti-FcεRI Ig in the sample or plasma fraction indicates that the sample or plasma fraction is not suitable for use in the production of an Ig preparation for administration to an individual.

[0447] 7. The method in any of paragraphs 1 to 6, wherein the method further includes administering the plasma sample or a fraction thereof to the individual if anti-FcεRI Ig is not present in a detectable quantity.

[0448] 8. The method of any of paragraphs 1 to 8, in which the Petition 870250100974, dated 04 / 11 / 2025, p. 103 / 216 The 98 / 172 method further comprises the inclusion of the plasma sample or a fraction thereof in a combined blood plasma sample if anti-FcεRI Ig is not present in a detectable quantity.

[0449] 9. The method of any of paragraphs 1 to 8, wherein the method further includes the exclusion of the plasma sample or a fraction thereof from a pooled blood plasma sample if anti-FcεRI Ig is present in a detectable quantity.

[0450] 10. The method in any of paragraphs 1 to 9, wherein the method further includes contact of the complex with a detection protein.

[0451] 11. The method of paragraph 10, wherein the detection protein comprises a detectable marker, wherein the presence of the detectable marker is indicative of the presence of a detectable amount of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0452] 12. The method of paragraphs 10 or 11, in which the detection protein comprises a variable region of antibody that binds to antiFceRI Ig.

[0453] 13. The method of paragraph 10, wherein the method further comprises contact of the detection protein with an antibody that binds to it and comprises a detectable marker.

[0454] 14. A method for detecting an Fc epsilon I anti-receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, the method includes:

[0455] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0456] (ii) detect the complex with a detection protein containing a detectable marker, and the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0457] 15. A method for screening a plasma sample or a fraction thereof for an Fc epsilon I antireceptor immunoglobulin (Ig) (FcεRI), the Petition 870250100974, dated 04 / 11 / 2025, p. 104 / 216 The 99 / 172 method includes:

[0458] (i) bring the sample into contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0459] (ii) detect the complex with a detection protein containing a detectable marker, and the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0460] 16. A method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, the method includes:

[0461] (i) bringing the sample into contact with a ligand that binds to an Fc epsilon I receptor (FcεRI) immunoglobulin (Ig) in the sample to form a complex; and

[0462] (ii) detect the complex with a detection protein containing a detectable marker, wherein the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0463] 17. A method for screening a plasma sample or a fraction thereof to determine its suitability for administration to an individual, the method comprises:

[0464] (i) bring the sample into contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (FcεRI) in the sample to form a complex; and

[0465] (ii) detect the complex with a detection protein containing a detectable marker, wherein the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual. Petition 870250100974, dated 04 / 11 / 2025, pp. 105 / 216 100 / 172

[0466] 18. A method for identifying a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0467] (i) bring the sample into contact with a ligand that binds to an Fc epsilon I receptor anti-Ig (FcεRI) immunoglobulin in the sample to form a complex; and

[0468] (ii) detect the complex with a detection protein containing a detectable marker, wherein the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the plasma sample or fraction thereof is not suitable for use in the production of an Ig preparation for administration to an individual.

[0469] 19. A method for screening a plasma sample or fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0470] (i) bring the sample into contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (FcεRI) in the sample to form a complex; and

[0471] (ii) detect the complex with a detection protein containing a detectable marker, and the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for use in the production of an Ig preparation for administration to an individual.

[0472] 20. The method in any of paragraphs 14 to 19, wherein the method further includes contact of the complex with a detection protein.

[0473] 21. The method of any of paragraphs 14 to 20, wherein the detection protein comprises a variable region of antibody that binds to anti-FcεRI Ig.

[0474] 22. The method of any of paragraphs 1 to 21, in which the Petition 870250100974, dated 04 / 11 / 2025, pp. 106 / 216 Binder 101 / 172 is immobilized on a solid surface.

[0475] 23. The method in any of paragraphs 1 to 22, wherein the method further includes immobilization of the binder on a solid surface.

[0476] 24. A method for detecting an Fc epsilon I anti-receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, the method includes:

[0477] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0478] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0479] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig and in which the detection protein comprises a detectable marker; and

[0480] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0481] 25. A method for detecting an Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, the method includes:

[0482] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0483] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0484] (iii) contact of the complex with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig;

[0485] (iv) placing the detection protein in contact with an antibody Petition 870250100974, dated 04 / 11 / 2025, pp. 107 / 216 102 / 172 that binds to it and contains a detectable marker; and

[0486] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0487] 26. A method for screening a plasma sample or a fraction thereof for an Fc epsilon I antireceptor immunoglobulin (Ig), the method comprises:

[0488] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0489] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0490] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig and in which the detection protein comprises a detectable marker; and

[0491] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0492] 27. A method for screening a plasma sample or a fraction thereof for an Fc epsilon I receptor immunoglobulin (Ig), the method comprises:

[0493] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0494] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0495] (iii) contact of the complex with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig; Petition 870250100974, dated 04 / 11 / 2025, pp. 108 / 216 103 / 172

[0496] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0497] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0498] 28. A method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, the method comprises:

[0499] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0500] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0501] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig and in which the detection protein comprises a detectable marker; and

[0502] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0503] 29. A method for identifying a plasma sample or a fraction thereof suitable for administration to an individual, the method includes:

[0504] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0505] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0506] (iii) contact of the complex with a detection protein that Petition 870250100974, dated 04 / 11 / 2025, pp. 109 / 216 104 / 172 comprises a variable antibody region, in which the detection protein binds to anti-FcεRI Ig;

[0507] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0508] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0509] 30. A method for screening a plasma sample or a fraction thereof to determine its suitability for administration to an individual, the method comprises:

[0510] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0511] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0512] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig and in which the detection protein comprises a detectable marker; and

[0513] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0514] 31. A method for screening a plasma sample or a fraction thereof to determine its suitability for administration to an individual, the method comprises:

[0515] (i) immobilization of a ligand comprising an FcεRI or Petition 870250100974, dated 04 / 11 / 2025, pp. 110 / 216 105 / 172 fragment or epitope of it on a solid surface;

[0516] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0517] (iii) contact of the complex with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig;

[0518] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0519] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for administration to the individual.

[0520] 32. A method for identifying a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0521] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0522] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0523] (iii) bring the complex into contact with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig and in which the detection protein comprises a detectable marker; and

[0524] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable Petition 870250100974, dated 04 / 11 / 2025, pp. 111 / 216 106 / 172 for use in the production of an Ig preparation for administration to an individual.

[0525] 33. A method for identifying a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0526] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0527] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0528] (iii) contact of the complex with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig;

[0529] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0530] (v) detect the marker, wherein the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for use in the production of an Ig preparation for administration to an individual.

[0531] 34. A method for screening a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0532] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0533] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0534] (iii) bring the complex into contact with a detection protein Petition 870250100974, dated 04 / 11 / 2025, pp. 112 / 216 107 / 172 comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig and in which the detection protein comprises a detectable marker; and

[0535] (iv) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for use in the production of an Ig preparation for administration to an individual.

[0536] 35. A method for screening a plasma sample or a fraction thereof for use in the production of an immunoglobulin (Ig) preparation for administration to an individual, the method comprises:

[0537] (i) immobilization of a ligand comprising an FcεRI or fragment or epitope thereof on a solid surface;

[0538] (ii) placing the sample in contact with the ligand immobilized on the solid surface, wherein the immobilized ligand binds to the anti-FcεRI Ig in the sample to form a complex;

[0539] (iii) contact of the complex with a detection protein comprising a variable antibody region, in which the detection protein binds to anti-FcεRI Ig;

[0540] (iv) bring the detection protein into contact with an antibody that binds to it and contains a detectable marker; and

[0541] (v) detect the marker, and the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the sample or fraction of plasma is not suitable for use in the production of Ig preparation for administration to an individual.

[0542] 36. The method of any of paragraphs 13 to 35, wherein, if the marker is not detected, anti-FcεRI Ig will not be present in a detectable quantity. Petition 870250100974, dated 04 / 11 / 2025, pp. 113 / 216 108 / 172

[0543] 37. The method in paragraph 36, wherein the method further includes administering a sample of plasma or a fraction thereof to an individual if anti-FcεRI Ig is not present in a detectable quantity.

[0544] 38. The method of paragraph 36, wherein the method further comprises the inclusion of the plasma sample or a fraction thereof in a combined blood plasma sample if anti-FcεRI Ig is not present in a detectable quantity.

[0545] 39. The method in paragraph 36, wherein the method also includes excluding the plasma sample or a fraction thereof from a pooled blood plasma sample if anti-FcεRI Ig is present in a detectable quantity.

[0546] 40. A method for identifying an individual suitable for plasma donation for the production of an immunoglobulin (Ig) preparation, the method includes:

[0547] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to anti-FcεRI Ig in the sample to form a complex; and

[0548] (ii) detect the complex, the presence of which is indicative of the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof.

[0549] 41. A screening method for an individual suitable for plasma donation for the production of an immunoglobulin (Ig) preparation, the method comprises:

[0550] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0551] (ii) detect the complex, the presence of the complex being indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0552] 42. The method of paragraphs 40 or 41, whereby the individual is suitable for plasma donation if anti-FcεRI Ig is not present.

[0553] 43. The method of either paragraph 40 or 41, in which the Petition 870250100974, dated 04 / 11 / 2025, pages 114 / 216 109 / 172 The individual is not suitable for plasma donation if anti-FcεRI Ig is present.

[0554] 44. The method in any of paragraphs 40 to 43, wherein the method further includes contact of the complex with a detection protein.

[0555] 45. The method of paragraph 44, in which the detection protein comprises a variable antibody region, where the detection protein binds to anti-FcεRI Ig.

[0556] 46. The method in paragraphs 44 or 45, wherein the detection protein comprises a detectable marker, wherein the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0557] 47. The method of paragraph 46, wherein the method further includes marker detection, wherein the presence of the detectable marker is indicative of the presence of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0558] 48. The method of paragraphs 44 or 45, wherein the method further comprises contact of the detection protein with an antibody that binds to it and comprises a detectable marker.

[0559] 49. A method for identifying an individual suitable for plasma donation for the production of an immunoglobulin (Ig) preparation, the method comprises:

[0560] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0561] (ii) detect the complex with a detection protein containing a detectable marker, wherein the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, wherein the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the individual is suitable for plasma donation for the production of an Ig preparation.

[0562] 50. A method of screening an individual suitable for Petition 870250100974, dated 04 / 11 / 2025, pages 115 / 216 110 / 172 Plasma donation for the production of an immunoglobulin (Ig) preparation, the method comprises:

[0563] (i) placing a sample or fraction of plasma from the individual in contact with a ligand that binds to an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the sample to form a complex; and

[0564] (ii) detect the complex with a detection protein containing a detectable marker, and the presence of a detectable marker indicates the presence of anti-FcεRI Ig in the plasma sample or fraction thereof, and the presence of anti-FcεRI Ig in the plasma sample or fraction thereof indicates that the individual is suitable for plasma donation for the production of an Ig preparation.

[0565] 51. The method of any of the paragraphs 40 to 50, in which the binder is immobilized on a solid surface.

[0566] 52. The method of any of paragraphs 40 to 51, wherein the method also includes immobilization of the binder on a solid surface.

[0567] 53. The method of any of the paragraphs 49 to 52, in which the individual is suitable for plasma donation if anti-FcεRI Ig is not present in a detectable quantity.

[0568] 54. The method described in any of paragraphs 49 to 52, where the individual is not suitable for plasma donation if anti-FcεRI Ig is present in a detectable quantity.

[0569] 55. The method in any of paragraphs 1 to 54, where the method is an enzyme-linked immunosorbent assay (ELISA).

[0570] 56. The method in any of paragraphs 1 to 54, where the method is a fluorescence-linked immunosorbent assay (FLISA).

[0571] 57. The method of any of the paragraphs 1 to 54, where the method is a lateral flow test.

[0572] 58. The method described in any of paragraphs 1 to 57, wherein anti-FcεRI Ig binds to an FcεRI epitope and activates an FcεRI-mediated signaling pathway. Petition 870250100974, dated 04 / 11 / 2025, pp. 116 / 216 111 / 172

[0573] 59. The method described in any of paragraphs 1 to 58, wherein anti-FcεRI Ig binds to an α chain of FcεRI and activates an FcεRI-mediated signaling pathway.

[0574] 60. The method described in any of paragraphs 1 to 59, in which a detectable amount of an anti-FcεRI Ig in the plasma sample or fraction thereof activates the FcεRI-mediated signaling pathway.

[0575] 61. The method of paragraph 59 or 60, in which activation of the FcεRI-mediated signaling pathway induces basophil activation.

[0576] 62. The method of any of paragraphs 1 to 61, in which activation of the FcεRI-mediated signaling pathway induces mast cell activation.

[0577] 63. The method of any of paragraphs 1 to 62, in which activation of the FcεRI-mediated signaling pathway induces basophil degranulation.

[0578] 64. The method of any of paragraphs 1 to 63, in which activation of the FcεRI-mediated signaling pathway induces mast cell degranulation.

[0579] 65. A method comprising contacting a plasma sample or a fraction thereof with a reagent that binds to an Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in the plasma sample or a fraction thereof and detecting the binding of the reagent.

[0580] 66. The method of paragraph 65, in which the reagent binds directly to anti-FcεRI Ig in the plasma sample or fraction thereof.

[0581] 67. The method of paragraph 65, in which the reagent binds indirectly to anti-FcεRI Ig in the plasma sample or fraction thereof.

[0582] 68. The method of paragraphs 65 or 66, wherein the reagent comprises a ligand which includes FcεRI or a fragment or epitope thereof.

[0583] 69. A method for detecting Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or plasma fraction, the method which includes determining the proportion of activation and / or degranulation of Petition 870250100974, dated 04 / 11 / 2025, pp. 117 / 216 112 / 172 basophils and / or mast cells induced by the plasma sample or plasma fraction, where the presence of activation and / or degranulation of basophils and / or mast cells is indicative of the presence of anti-FcεRI Ig in the plasma sample or plasma fraction.

[0584] 70. The method of any of paragraphs 1 to 69, wherein Ig anti-FcεRI is an IgG anti-FcεRI and an IgE anti-FcεRI.

[0585] 71. The method of any of paragraphs 1 to 70, wherein Ig anti-FcεRI is an IgG anti-FcεRI.

[0586] 72. The method of paragraphs 70 or 71, in which IgG anti-FcεRI is an IgG1.

[0587] 73. The method of paragraphs 70 or 71, in which IgG anti-FcεRI is an IgG2.

[0588] 74. The method of paragraph 70 or 71, in which IgG anti-FcεRI is an IgG3.

[0589] 75. The method of paragraph 70 or 71, in which IgG anti-FcεRI is an IgG4.

[0590] 76. The method of any of paragraphs 1 to 69, where Ig anti-FcεRI is an IgE anti-FcεRI.

[0591] 77. The method of any of paragraphs 1 to 69, where Ig anti-FcεRI is an IgM anti-FcεRI.

[0592] 78. The method of any of paragraphs 1 to 69, where Ig anti-FcεRI is an IgA anti-FcεRI.

[0593] 79. The method of any of paragraphs 1 to 78, wherein the ligand comprises an FcεRI or a fragment or epitope thereof.

[0594] 80. The method of any of paragraphs 1 to 78, wherein the ligand is an FcεRI or a fragment or epitope thereof.

[0595] 81. The method of any of paragraphs 1 to 78, wherein the ligand comprises an FcεRI antibody or a fragment thereof.

[0596] 82. The method of any of paragraphs 1 to 78, wherein the ligand comprises an FcεRI DNA aptamer. Petition 870250100974, dated 04 / 11 / 2025, pp. 118 / 216 113 / 172

[0597] 83. The method of any of the paragraphs 1 to 82, wherein the detection protein is an anti-IgG antibody.

[0598] 84. The method of paragraph 83, in which the detection protein is an anti-IgG1 antibody.

[0599] 85. The method of paragraph 83, in which the detection protein is an anti-IgG2 antibody.

[0600] 86. The method of paragraph 83, in which the detection protein is an anti-IgG3 antibody.

[0601] 87. The method of paragraph 84, in which the detection protein is an anti-IgG4 antibody.

[0602] 88. The method of any of paragraphs 1 to 82, wherein the detection protein is an anti-IgE antibody.

[0603] 89. The method of any of paragraphs 1 to 82, wherein the detection protein is an anti-IgM antibody.

[0604] 90. The method of any of paragraphs 1 to 82, wherein the detection protein is an anti-IgA antibody.

[0605] 91. The method of any of paragraphs 1 to 90, wherein the detectable marker is selected from the group consisting of a radiotracer, an enzyme, a fluorescent marker, a luminescent marker, a bioluminescent marker, a magnetic marker, a prosthetic group and a contrast agent.

[0606] 92. The method of any of paragraphs 1 to 91, wherein the detectable marker is a radio tracer.

[0607] 93. The method in any of paragraphs 1 to 91, where the detectable marker is an enzyme.

[0608] 94. The method of any of paragraphs 1 to 91, where the detectable marker is a fluorescent marker.

[0609] 95. The method of any of paragraphs 1 to 91, where the detectable marker is a luminescent marker.

[0610] 96. The method of any of paragraphs 1 to 91, in which the Petition 870250100974, dated 04 / 11 / 2025, pp. 119 / 216 114 / 172 detectable marker is a bioluminescent marker.

[0611] 97. The method of any of paragraphs 1 to 91, where the detectable marker is a magnetic marker.

[0612] 98. The method of any of paragraphs 1 to 91, in which the detectable marker is a prosthetic group.

[0613] 99. The method of any of paragraphs 1 to 91, in which the detectable marker is a contrast agent.

[0614] 100. The method of any of paragraphs 1 to 99, and the method further includes the determination of the level of anti-FcεRI Ig in the plasma sample or fraction thereof.

[0615] 101. The method of paragraphs 98 or 99, wherein the method further includes administering the plasma sample or a fraction thereof to the individual if the level of anti-FcεRI IgG is below a detectable amount.

[0616] 102. The method of paragraph 100 or 101, where Ig anti-FcεRI is an IgG anti-FcεRI.

[0617] 103. The method of paragraphs 101 or 102, in which the detectable amount of anti-FcεRI IgG in the plasma sample or fraction thereof is at least 40 μg / mL.

[0618] 104. The method of paragraph 100, in which anti-FcεRI Ig is an anti-FcεRI IgE.

[0619] 105. The method of paragraph 104, in which the detectable amount of anti-FcεRI IgE in the plasma sample or fraction thereof is at least 0.1 kU / L.

[0620] 106. The method of any of paragraphs 1 to 105, wherein the method further includes the determination of the proportion of basophil activation induced by the plasma sample or fraction thereof.

[0621] 107. The method of paragraph 106, in which the activation ratio of basophils after exposure to the sample or plasma fraction is determined by determining the proportion of basophils expressing one or more selected markers from the group consisting of CD63, CD203c and their Petition 870250100974, dated 04 / 11 / 2025, pages 120 / 216 115 / 172 combinations in the total population of basophils exposed to the sample or plasma fraction.

[0622] 108. The method of paragraphs 106 or 107, in which the proportion of basophil activation after exposure to the sample or plasma fraction is determined by determining the proportion of basophils expressing CD63 in the total population of basophils exposed to the sample or plasma fraction.

[0623] 109. The method of paragraphs 106 or 107, in which the proportion of basophil activation after exposure to the sample or plasma fraction is determined by determining the proportion of basophils expressing CD203c in the total population of basophils exposed to the sample or plasma fraction.

[0624] 110. The method of paragraphs 106 or 107, in which the activation ratio of basophils after exposure to the sample or plasma fraction is determined by determining the proportion of basophils expressing CD63 and CD203c in the total population of basophils exposed to the sample or plasma fraction.

[0625] 111. The method of any of paragraphs 106 to 110, wherein the ratio of basophil activation induced by the plasma sample or fraction indicates whether a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof.

[0626] 112. The method of paragraphs 111, whereby a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14% or greater than 15% of the total population of basophils exposed to the plasma sample or fraction.

[0627] 113. The method in paragraphs 111 or 112, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample. Petition 870250100974, dated 04 / 11 / 2025, pp. 121 / 216 116 / 172 or a fraction thereof if the proportion of basophils expressing CD63 after exposure to the sample or plasma fraction is greater than 5% of the total population of basophils exposed to the sample or plasma fraction.

[0628] 114. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 6% of the total population of basophils exposed to the plasma sample or fraction.

[0629] 115. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 7% of the total population of basophils exposed to the plasma sample or fraction.

[0630] 116. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 8% of the total population of basophils exposed to the plasma sample or fraction.

[0631] 117. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 9% of the total population of basophils exposed to the plasma sample or fraction.

[0632] 118. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 10% of the total population of basophils exposed to the plasma sample or fraction.

[0633] 119. The method of paragraphs 111 or 112, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample. Petition 870250100974, dated 04 / 11 / 2025, pages 122 / 216 117 / 172 or a fraction thereof if the proportion of basophils expressing CD63 after exposure to the sample or plasma fraction is greater than 11% of the total population of basophils exposed to the sample or plasma fraction.

[0634] 120. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 12% of the total population of basophils exposed to the plasma sample or fraction.

[0635] 121. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 13% of the total population of basophils exposed to the plasma sample or fraction.

[0636] 122. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 14% of the total population of basophils exposed to the plasma sample or fraction.

[0637] 123. The method of paragraphs 111 or 112, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction is greater than 15% of the total population of basophils exposed to the plasma sample or fraction.

[0638] 124. The method of paragraphs 111 or 112, wherein the method further includes administering the plasma sample or a fraction thereof to the individual if anti-FcεRI Ig is not present in a detectable quantity in the plasma sample or a fraction thereof.

[0639] 125. The method of paragraph 124, in which anti-FcεRI Ig is not present in a detectable quantity if the proportion of basophils expressing CD63 after exposure to the plasma sample or fraction thereof is Petition 870250100974, dated 04 / 11 / 2025, pages 123 / 216 118 / 172 less than 5% of the total population of basophils exposed to the plasma sample or fraction thereof.

[0640] 126. The method of paragraph 111, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14% or greater than 15% of the total population of basophils exposed to the plasma sample or fraction.

[0641] 127. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 5% of the total population of basophils exposed to the plasma sample or fraction.

[0642] 128. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 6% of the total population of basophils exposed to the plasma sample or fraction.

[0643] 129. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 7% of the total population of basophils exposed to the plasma sample or fraction.

[0644] 130. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 8% of the total population of basophils exposed to the plasma sample or fraction.

[0645] 131. The method of paragraphs 111 or 126, in which a Petition 870250100974, dated 04 / 11 / 2025, pages 124 / 216 119 / 172 A detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 9% of the total population of basophils exposed to the plasma sample or fraction.

[0646] 132. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 10% of the total population of basophils exposed to the plasma sample or fraction.

[0647] 133. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 11% of the total population of basophils exposed to the plasma sample or fraction.

[0648] 134. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 12% of the total population of basophils exposed to the plasma sample or fraction.

[0649] 135. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 13% of the total population of basophils exposed to the plasma sample or fraction.

[0650] 136. The method of paragraphs 111 or 126, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 14% of the total population of basophils exposed to the plasma sample or fraction.

[0651] 137. The method of paragraphs 111 or 126, in which a Petition 870250100974, dated 04 / 11 / 2025, pages 125 / 216 120 / 172 A detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction is greater than 15% of the total population of basophils exposed to the plasma sample or fraction.

[0652] 138. The method of paragraphs 111 or 124, in which anti-FcεRI Ig is not present in a detectable quantity if the proportion of basophils expressing CD203c after exposure to the plasma sample or fraction thereof is less than 5%.

[0653] 139. The method of any of paragraphs 106 to 138, wherein the basophil activation ratio is determined by incubating basophils with the plasma sample or a fraction thereof and quantifying the proportion of basophils expressing CD63 and / or the proportion of basophils expressing CD203c in the total basophil population using flow cytometry.

[0654] 141. The method of any of paragraphs 1 to 139, wherein the method further includes the determination of the proportion of mast cell activation induced by the plasma sample or fraction thereof.

[0655] 142. The method of paragraph 141, in which the proportion of mast cell activation after exposure to the plasma sample or fraction thereof is determined by determining the proportion of mast cells expressing CD107a in the total population of mast cells exposed to the plasma sample or fraction thereof.

[0656] 143. The method of either paragraph 141 or 142, wherein the proportion of mast cell activation induced by the plasma sample or fraction indicates whether a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof.

[0657] 144. The method of paragraph 143, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 5%, greater than 6%, greater than Petition 870250100974, dated 04 / 11 / 2025, pages 126 / 216 121 / 172 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14%, or greater than 15% of the total mast cell population exposed to the sample or plasma fraction.

[0658] 145. The method of paragraphs 143 or 144, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 5% of the total mast cell population exposed to the plasma sample or fraction.

[0659] 146. The method of paragraphs 143 or 144, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 6% of the total mast cell population exposed to the plasma sample or fraction.

[0660] 147. The method of paragraphs 143 or 144, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 7% of the total mast cell population exposed to the plasma sample or fraction.

[0661] 148. The method of paragraphs 143 or 144, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 8% of the total mast cell population exposed to the plasma sample or fraction.

[0662] 149. The method of paragraphs 143 or 144, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 9% of the total mast cell population exposed to the plasma sample or fraction.

[0663] 150. The method of paragraphs 143 or 144, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample. Petition 870250100974, dated 04 / 11 / 2025, pages 127 / 216 122 / 172 or a fraction thereof if the proportion of mast cells expressing CD107a after exposure to the sample or plasma fraction is greater than 10% of the total mast cell population exposed to the sample or plasma fraction.

[0664] 151. The method of paragraphs 143 or 144, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 11% of the total mast cell population exposed to the plasma sample or fraction.

[0665] 152. The method of paragraphs 143 or 144, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 12% of the total mast cell population exposed to the plasma sample or fraction.

[0666] 153. The method of paragraphs 143 or 144, wherein a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 13% of the total mast cell population exposed to the plasma sample or fraction.

[0667] 154. The method of paragraphs 143 or 144, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 14% of the total mast cell population exposed to the plasma sample or fraction.

[0668] 155. The method of paragraphs 143 or 144, in which a detectable amount of anti-FcεRI Ig is present in the plasma sample or fraction thereof if the proportion of mast cells expressing CD107a after exposure to the plasma sample or fraction is greater than 15% of the total mast cell population exposed to the plasma sample or fraction.

[0669] 156. The method of paragraph 143 or 144, in which anti-FcεRI Ig is not present in the plasma sample or fraction thereof in an amount Petition 870250100974, dated 04 / 11 / 2025, pages 128 / 216 123 / 172 detectable if the proportion of mast cells expressing CD107a after exposure to the sample or plasma fraction is less than 5%.

[0670] 157. The method of any of paragraphs 143 to 156, in which the mast cell activation ratio is determined by incubating mast cells with the plasma sample or a fraction thereof and quantifying the proportion of mast cells expressing CD107a in the total mast cell population using flow cytometry.

[0671] 158. The method of any of paragraphs 1 to 157, wherein the plasma sample or fraction is selected from the group consisting of a human blood plasma sample, an IgG intermediate product, an intravenous immunoglobulin G (IVIG), a subcutaneous immunoglobulin G (SCIG), a cryo-rich plasma, a cryo-poor plasma, a Supernatant I (SN I), a Cohn Fraction II (Fr II), a Cohn Fraction II+III (Fr II+III), a Cohn Fraction I+II+III (FrI+II+III), a Kistler / Nitschmann Precipitate A (KN A), a Kistler / Nitschmann Precipitate B (KN B), a Kistler / Nitschmann Precipitate B from the Supernatant (KN B+1) and combinations thereof.

[0672] 159. The method of any of the paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a sample of human blood plasma.

[0673] 160. The method of any of the paragraphs 1 to 158, wherein the plasma sample or fraction thereof is an IgG intermediate product.

[0674] 161. The method of any of paragraphs 1 to 158, wherein the plasma sample or fraction thereof is an intravenous immunoglobulin G (IVIG).

[0675] 162. The method of any of paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a subcutaneous immunoglobulin G (SCIG).

[0676] 163. The method of any of paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a cryo-poor plasma.

[0677] 164. The method of any of paragraphs 1 to 158, in which the Petition 870250100974, dated 04 / 11 / 2025, pp. 129 / 216 124 / 172 plasma sample or fraction thereof is a Supernatant I (SN I).

[0678] 165. The method of any of paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a Cohn Fraction II (Fr II).

[0679] 166. The method of any of paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a Cohn Fraction II+III (Fr II+III).

[0680] 167. The method of any of the paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a Cohn Fraction I+II+III (FrI+II+III).

[0681] 168. The method of any of the paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a Kistler / Nitschmann Precipitate A (KN A).

[0682] 169. The method of any of paragraphs 1 to 158, wherein the plasma sample or fraction thereof is a Kistler / Nitschmann Precipitate B (KN B).

[0683] 170. The method of any of paragraphs 1 to 158, wherein the sample or plasma fraction is a Kistler / Nitschmann Supernatant Precipitate B (KN B+1).

[0684] 171. The method of any of paragraphs 1 to 170, wherein the sample or plasma fraction is a sample of human blood plasma from one or more individuals.

[0685] 172. An affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in an affinity chromatography resin matrix.

[0686] 173. The affinity chromatography resin of paragraph 172, wherein the resin further comprises a blood group A antigen and a blood group B antigen immobilized on the affinity chromatography resin matrix.

[0687] 174. A method for preparing a reduced preparation of Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) from a plasma sample or fraction thereof, the method comprising binding the anti-FcεRI Ig to an affinity chromatography resin comprising a Petition 870250100974, dated 04 / 11 / 2025, pages 130 / 216 125 / 172 ligand that binds to anti-FcεRI Ig in the plasma sample or fraction thereof and collection of the reduced anti-FcεRI Ig preparation.

[0688] 175. The method of paragraph 174, wherein the method further comprises loading the plasma sample or fraction thereof onto the affinity chromatography resin.

[0689] 176. Method for preparing a reduced preparation of Fc epsilon I antireceptor immunoglobulin (Ig) (FcεRI) from a plasma sample or a fraction thereof, the method comprises

[0690] (i) loading the plasma sample or a fraction thereof onto an affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig in the plasma sample or a fraction thereof immobilized on an affinity chromatography resin matrix; and

[0691] (ii) collect the reduced anti-FcεRI Ig preparation.

[0692] 177. The method of any of paragraphs 174 to 176, wherein the method also includes a washing and / or elution step.

[0693] 178. The method of any of paragraphs 174 to 177, and the method further includes an elucidation step.

[0694] 179. The method of any of paragraphs 174 to 178, and the method further includes a washing step.

[0695] 180. The method of any of paragraphs 174 to 179, in which anti-FcεRI Ig binds to an α chain of FcεRI and activates an FcεRI-mediated signaling pathway.

[0696] 181. The method of any of paragraphs 174 to 180, in which the reduced anti-FcεRI Ig preparation induces reduced activation of an FcεRI-mediated signaling pathway compared to a preparation in which the anti-FcεRI Ig is not reduced.

[0697] 182. The method of any of the paragraphs 174 to 181, in which anti-FcεRI Ig is not present in a detectable quantity in the reduced anti-FcεRI Ig preparation.

[0698] 183. The method of paragraph 182, in which reduced preparation Petition 870250100974, dated 04 / 11 / 2025, pp. 131 / 216 126 / 172 of anti-FcεRI Ig induces reduced activation of an FcεRI-mediated signaling pathway compared to a preparation in which anti-FcεRI Ig is not reduced.

[0699] 184. The method of any of the paragraphs 174 to 182, in which anti-FcεRI Ig is not present in a detectable quantity and the reduced anti-FcεRI Ig preparation induces a reduction in basophil activation compared to a preparation in which anti-FcεRI Ig is not reduced.

[0700] 185. The method of any of the paragraphs 174 to 182, in which anti-FcεRI Ig is not present in a detectable quantity and the reduced anti-FcεRI Ig preparation induces a reduction in mast cell activation compared to a preparation in which anti-FcεRI Ig is not reduced.

[0701] 186. The method of any of paragraphs 174 to 184, in which basophil activation after exposure to the reduced antiFcεRI Ig preparation is determined by determining the proportion of basophils expressing one or more selected markers from the group consisting of CD63, CD203c and their combinations.

[0702] 187. The method of paragraph 186, in which basophil activation is determined by determining the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation.

[0703] 188. The method of paragraph 186, in which basophil activation is determined by determining the proportion of CD203c basophils after exposure to the reduced anti-FcεRI Ig preparation.

[0704] 189. The method of paragraph 186, in which basophil activation is determined by determining the proportion of basophils expressing CD63 and CD203c after exposure to the reduced anti-FcεRI Ig preparation.

[0705] 190. The method of any of the paragraphs 186, 187 or 189, in which the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 1%, less than 2%, less Petition 870250100974, dated 04 / 11 / 2025, pp. 132 / 216 127 / 172 that 3%, less than 4%, or less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0706] 191. The method of any of paragraphs 186, 187, 189 or 190, in which the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0707] 192. The method of any of paragraphs 186, 187, 189 to 191, in which the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 4% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0708] 193. The method of any of paragraphs 186, 187, 189 to 192, in which the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 3% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0709] 194. The method of any of paragraphs 186, 187, 189 to 193, in which the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 2% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0710] 195. The method of any of paragraphs 186, 187, 189 to 194, in which the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 1% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0711] 196. The method of any of paragraphs 186, 187 or 189, wherein the method further includes administration of the reduced anti-FcεRI Ig preparation to the individual if the proportion of basophils expressing CD63 Petition 870250100974, dated 04 / 11 / 2025, pp. 133 / 216 128 / 172 after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total basophil population exposed to the reduced anti-FcεRI Ig preparation.

[0712] 197. The method of any of paragraphs 186, 187 or 189, wherein the method or use further comprises the inclusion of the reduced anti-FcεRI Ig preparation in a blood plasma sample if the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0713] 198. The method of any of paragraphs 186, 187 or 189, wherein the method or use further includes the exclusion of the reduced anti-FcεRI Ig preparation from a pooled blood plasma sample if the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is greater than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0714] 199. The method of any of the paragraphs 186, 187 or 189, in which the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0715] 200. The method of any of paragraphs 186, 187, 189 or 199, in which the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0716] 201. The method of any of paragraphs 186, 187, 189, 199 or 200, in which the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 4% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation. Petition 870250100974, dated 04 / 11 / 2025, pp. 134 / 216 129 / 172

[0717] 202. The method of any of paragraphs 186, 187, 189, 199 to 201, in which the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 3% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0718] 203. The method of any of paragraphs 186, 187, 189, 199 to 202, in which the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 2% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0719] 204. The method of any of paragraphs 186, 187, 189, 199 to 203, in which the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 1% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0720] 205. The method of any of paragraphs 186, 187 or 189, wherein the method further includes administration of the reduced anti-FcεRI Ig preparation to the individual if the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0721] 206. The method of any of paragraphs 186, 187 or 189, wherein the method further comprises the inclusion of the reduced anti-FcεRI Ig preparation in a blood plasma sample if the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation.

[0722] 207. The method of any of paragraphs 186, 187 or 189, wherein the method further includes the exclusion of the reduced anti-FcεRI Ig preparation from a combined blood plasma sample if the proportion of Petition 870250100974, dated 04 / 11 / 2025, pp. 135 / 216 130 / 172 basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is greater than 5% of the total basophil population exposed to the reduced anti-FcεRI Ig preparation.

[0723] 208. The method of any of paragraphs 185 to 207, in which mast cell activation after exposure to the reduced anti-FcεRI Ig preparation is determined by determining the proportion of mast cells expressing CD107a.

[0724] 209. The method of paragraph 208, in which the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 1%, less than 2%, less than 3%, less than 4%, or less than 5% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0725] 210. The method in paragraphs 208 or 210, wherein the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0726] 211. The method of paragraphs 208 to 210, in which the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 4% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0727] 212. The method of paragraphs 208 to 211, in which the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 3% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0728] 213. The method of paragraphs 208 to 212, in which the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 2% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0729] 214. The method of paragraphs 208 to 213, in which the proportion of mast cells expressing CD107a after exposure to the reduced preparation Petition 870250100974, dated 04 / 11 / 2025, pp. 136 / 216 131 / 172 of anti-FcεRI Ig is less than 1% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0730] 215. The method of paragraphs 208 to 214, wherein the method further includes administering the reduced anti-FcεRI Ig preparation to the individual if the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0731] 216. The method of paragraphs 208 to 214, wherein the method further comprises the inclusion of the reduced anti-FcεRI Ig preparation in a pooled blood plasma sample if the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0732] 217. The method of paragraphs 208 to 214, wherein the method further includes the exclusion of the reduced anti-FcεRI Ig preparation from a pooled blood plasma sample if the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is greater than 5% of the total mast cell population exposed to the reduced anti-FcεRI Ig preparation.

[0733] ​​218. The method of any of paragraphs 186 to 198, in which the basophil activation ratio is determined by incubating basophils with the reduced anti-FcεRI Ig preparation and quantifying the proportion of CD63-expressing basophils in the total basophil population using flow cytometry.

[0734] 219. The method of any of paragraphs 199 to 207, in which the basophil activation ratio is determined by incubating basophils with the reduced anti-FcεRI Ig preparation and quantifying the proportion of basophils expressing CD203c in the total basophil population using flow cytometry.

[0735] 220. The method of any of paragraphs 208 to 217, in which Petition 870250100974, dated 04 / 11 / 2025, pp. 137 / 216 132 / 172 The mast cell activation ratio is determined by incubating mast cells with the reduced anti-FcεRI Ig preparation and quantifying the proportion of mast cells expressing CD107a in the total mast cell population using flow cytometry.

[0736] 221. The method of any of paragraphs 174 to 220, wherein the reduced anti-FcεRI Ig preparation comprises less than 40 μg / mL of an anti-FcεRI IgG.

[0737] 222. The method of any of paragraphs 174 to 221, wherein the reduced anti-FcεRI Ig preparation comprises less than 35 μg / mL of an anti-FcεRI IgG.

[0738] 223. The method of any of paragraphs 174 to 222, wherein the reduced anti-FcεRI Ig preparation comprises less than 30 μg / mL of an anti-FcεRI IgG.

[0739] 224. The method of any of paragraphs 174 to 223, wherein the reduced anti-FcεRI Ig preparation comprises less than 25 μg / mL of an anti-FcεRI IgG.

[0740] 225. The method of any of paragraphs 174 to 224, wherein the reduced anti-FcεRI Ig preparation comprises less than 20 μg / mL of an anti-FcεRI IgG.

[0741] 226. The method of any of paragraphs 174 to 225, wherein the reduced anti-FcεRI Ig preparation comprises less than 15 μg / mL of an anti-FcεRI IgG.

[0742] 227. The method of any of paragraphs 174 to 226, wherein the reduced anti-FcεRI Ig preparation comprises less than 10 μg / mL of an anti-FcεRI IgG.

[0743] 228. The method of any of paragraphs 174 to 227, wherein the reduced anti-FcεRI Ig preparation comprises less than 5 μg / mL of an anti-FcεRI IgG.

[0744] 229. The method of any of paragraphs 174 to 228, in which the reduced anti-FcεRI Ig preparation comprises between 0-39.9 μg / mL of Petition 870250100974, dated 04 / 11 / 2025, pp. 138 / 216 133 / 172 an anti-FcεRI IgG.

[0745] 230. The method of any of paragraphs 174 to 229, wherein the reduced anti-FcεRI Ig preparation comprises between 0-30 μg / mL of an anti-FcεRI IgG.

[0746] 231. The method of any of paragraphs 174 to 230, wherein the reduced anti-FcεRI Ig preparation comprises between 0-20 μg / mL of an anti-FcεRI IgG.

[0747] 232. The method of any of paragraphs 174 to 231, wherein the reduced anti-FcεRI Ig preparation comprises between 0-10 μg / mL of an anti-FcεRI IgG.

[0748] 233. The method of any of paragraphs 174 to 232, wherein the reduced anti-FcεRI Ig preparation comprises less than 0.1 kU / L of an anti-FcεRI IgE.

[0749] 234. The method of any of paragraphs 174 to 233, wherein the reduced anti-FcεRI Ig preparation comprises less than 0.05 kU / L of an anti-FcεRI IgE.

[0750] 235. The method of any of paragraphs 174 to 234, wherein the reduced anti-FcεRI Ig preparation comprises less than 0.01 kU / L of an anti-FcεRI IgE.

[0751] 236. The method of any of paragraphs 174 to 235, wherein the reduced anti-FcεRI Ig preparation comprises less than 0.001 kU / L of an anti-FcεRI IgE.

[0752] 237. The method of any of paragraphs 174 to 236, wherein the reduced anti-FcεRI Ig preparation comprises 0 kU / L of an anti-FcεRI IgE.

[0753] 238. The method of any of paragraphs 174 to 237, in which the reduced preparation of anti-FcεRI Ig is between 0-0.1 kU / L of an anti-FcεRI IgE.

[0754] 239. The method of any of paragraphs 174 to 238, in which the reduced preparation of anti-FcεRI Ig between 0.05 and 0.1 kU / L of an anti-IgE Petition 870250100974, dated 04 / 11 / 2025, p. 139 / 216 134 / 172 FceRI.

[0755] 240. The method of any of paragraphs 174 to 239, wherein the affinity chromatography resin further comprises a blood group A antigen immobilized on the affinity chromatography resin matrix.

[0756] 241. The method of any of paragraphs 174 to 240, wherein the affinity chromatography resin is a continuous affinity chromatography resin.

[0757] 242. The method of paragraphs 240 or 241, wherein affinity chromatography is continuous affinity chromatography comprising:

[0758] (i) a first affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a first affinity chromatography resin matrix; and

[0759] (ii) a second affinity chromatography resin comprising a blood group A antigen immobilized on a matrix of the second affinity chromatography resin.

[0760] 243. The method of paragraphs 240 or 241, wherein affinity chromatography is continuous affinity chromatography comprising:

[0761] (i) a first affinity chromatography resin comprising a blood group A antigen immobilized on a second affinity chromatography resin matrix; and

[0762] (ii) a second affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a matrix of the first affinity chromatography resin.

[0763] 244. The method of any of paragraphs 174 to 243, wherein the affinity chromatography resin further comprises a blood group B antigen immobilized on the affinity chromatography resin matrix. Petition 870250100974, dated 04 / 11 / 2025, pages 140 / 216 135 / 172

[0764] 245. The method of paragraph 244, wherein affinity chromatography is a continuous affinity chromatography comprising:

[0765] (i) a first affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a first affinity chromatography resin matrix; and

[0766] (ii) a second affinity chromatography resin comprising a blood group B antigen immobilized on a matrix of the second affinity chromatography resin.

[0767] 246. The method of paragraph 244, wherein affinity chromatography is a continuous affinity chromatography comprising:

[0768] (i) a first affinity chromatography resin comprising blood group B antigen immobilized on a second affinity chromatography resin matrix; and

[0769] (ii) a second affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a matrix of the first affinity chromatography resin.

[0770] 247. The method of any of paragraphs 174 to 239, wherein the affinity chromatography resin further comprises a blood group A antigen and a blood group B antigen immobilized on the affinity chromatography resin matrix.

[0771] 248. The method of paragraph 247, wherein affinity chromatography is a continuous affinity chromatography comprising:

[0772] (i) a first affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized on a first affinity chromatography resin matrix; and

[0773] (ii) a second affinity chromatography resin comprising a blood group A antigen and a blood group B antigen immobilized on a matrix of the second affinity chromatography resin.

[0774] 249. The method of paragraph 247, in which chromatography of Petition 870250100974, dated 04 / 11 / 2025, pp. 141 / 216 136 / 172 affinity is a continuous affinity chromatography comprising:

[0775] (i) a first affinity chromatography resin comprising a blood group A antigen and a blood group B antigen immobilized on a second affinity chromatography resin matrix; and

[0776] (ii) a second affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig immobilized in a matrix of the first affinity chromatography resin.

[0777] 250. The method of any of paragraphs 1 to 249, wherein the ligand that binds to the anti-FcεRI Ig comprises an FcεRI or a fragment or epitope thereof.

[0778] 251. The method of any of the paragraphs from 1 to 250, wherein the method further comprises one or more steps selected from a group consisting of ethanol precipitation, octanoid acid fractionation, ion exchange chromatography, viral inactivation, viral filtration, ultrafiltration / diafiltration and combinations thereof.

[0779] 252. The method of paragraph 251, in which the method also includes the ethanol precipitation step.

[0780] 253. The method of paragraph 251 or 252, wherein the method further includes the step of fractionating the octanoid acid.

[0781] 254. The method in any of paragraphs 251 to 253, wherein the method also includes the ion-exchange chromatography step.

[0782] 255. The method of any of paragraphs 251 to 254, and the method further includes the viral inactivation step.

[0783] 256. The method of any of paragraphs 251 to 255, and the method further includes the viral filtering step.

[0784] 257. The method in any of paragraphs 1 to 256, wherein the method also includes the ultrafiltration / diafiltration step.

[0785] 258. A reduced IgG preparation of Fc epsilon I receptor immunoglobulin (Ig) (FcεRI), comprising polyclonal IgG. Petition 870250100974, dated 04 / 11 / 2025, pp. 142 / 216 137 / 172

[0786] 259. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 258, in which the polyclonal IgG is selected from the group consisting of Hizentra® (CSL Behring), Privigen® (CSL Behring), Flebogamma® (Grifols), Gamunex®-C (Grifols), Gammagard® (Takeda) and Octagam® (Octapharma), Xembify® (Grifols), Cutaquig® (Octapharma) and Cuvitru® (Takeda).

[0787] 260. The reduced IgG preparation of anti-FcεRI Ig of paragraphs 258 or 259, in which the preparation further includes a proline compound stabilizer, has a pH of about 4.2 to about 5.4.

[0788] 261. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 260, where proline is present at a concentration of 250 mM and where the pH is 4.8.

[0789] 262. The reduced IgG preparation of anti-FcεRI Ig from any of paragraphs 258 to 261, further comprising 20 pg / mL of PS80, in which proline is present at a concentration of 250 mM and in which the pH is 4.8.

[0790] 263. The reduced anti-FcεRI Ig IgG preparation of any of paragraphs 258 to 262, wherein the reduced anti-FcεRI Ig IgG preparation does not comprise any detectable amount of anti-FcεRI Ig and induces reduced activation of an FcεRI-mediated signaling pathway relative to an IgG preparation in which the anti-FcεRI Ig is not reduced.

[0791] 264. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 263, wherein the reduced IgG anti-FcεRI Ig preparation does not comprise any detectable amount of anti-FcεRI Ig and induces reduced basophil activation compared to a preparation in which the anti-FcεRI Ig is not reduced.

[0792] 265. The reduced anti-FcεRI Ig IgG preparation of any of paragraphs 258 to 264, wherein the reduced anti-FcεRI Ig IgG preparation does not comprise any detectable amount of anti-FcεRI Ig and induces reduced mast cell activation compared to a preparation in which the anti-FcεRI Ig is not reduced. Petition 870250100974, dated 04 / 11 / 2025, pp. 143 / 216 138 / 172

[0793] 266. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 265, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 40 μg / mL, less than 35 μg / mL, less than 30 μg / mL, less than 25 μg / mL, less than 20 μg / mL, less than 15 μg / mL, less than 10 μg / mL or less than 5 μg / mL of an anti-FcεRI IgG.

[0794] 267. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 40 μg / mL of anti-FcεRI IgG.

[0795] 268. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 35 μg / mL of anti-FcεRI IgG.

[0796] 269. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 30 μg / mL of anti-FcεRI IgG.

[0797] 270. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 25 μg / mL of anti-FcεRI IgG.

[0798] 271. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 20 μg / mL of anti-FcεRI IgG.

[0799] 272. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 15 μg / mL of anti-FcεRI IgG.

[0800] 273. Reduced IgG preparation of anti-FcεRI Ig from the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 10 μg / mL of anti-FcεRI IgG.

[0801] 274. Reduced IgG preparation of anti-FcεRI Ig from the paragraph 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 5 μg / mL of anti-FcεRI IgG.

[0802] 275. Reduced IgG preparation of anti-FcεRI Ig of the paragraph Petition 870250100974, dated 04 / 11 / 2025, pp. 144 / 216 139 / 172 266, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 1 μg / mL of anti-FcεRI IgG.

[0803] 276. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 40 μg / mL of anti-FcεRI IgG.

[0804] 277. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 35 μg / mL of anti-FcεRI IgG.

[0805] 278. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 30 μg / mL of anti-FcεRI IgG.

[0806] 279. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 25 μg / mL of anti-FcεRI IgG.

[0807] 280. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 20 μg / mL of anti-FcεRI IgG.

[0808] 281. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 15 μg / mL of anti-FcεRI IgG.

[0809] 282. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 10 μg / mL of anti-FcεRI IgG.

[0810] 283. Reduced IgG preparation of anti-FcεRI Ig from the paragraph 266, in which the reduced IgG anti-FcεRI Ig preparation comprises between 1 and 5 μg / mL of anti-FcεRI IgG.

[0811] 284. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 283, wherein the reduced IgG anti-FcεRI Ig preparation comprises less than 0.1 kU / L, less than 0.05 kU / L, less than 0.01 kU / L or less than 0.001 kU / L of anti-FcεRI IgE. Petition 870250100974, dated 04 / 11 / 2025, pp. 145 / 216 140 / 172

[0812] 285. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 284, in which the reduced IgG preparation of anti-FcεRI Ig comprises less than 0.1 kU / L of anti-FcεRI IgE.

[0813] 286. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 284, in which the reduced IgG preparation of anti-FcεRI Ig comprises less than 0.05 kU / L of anti-FcεRI IgE.

[0814] 287. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 284, in which the reduced IgG preparation of anti-FcεRI Ig comprises less than 0.01 kU / L of anti-FcεRI IgE.

[0815] 288. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 284, in which the reduced IgG preparation of anti-FcεRI Ig comprises less than 0.001 kU / L of anti-FcεRI IgE.

[0816] 289. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 284, in which the reduced IgG preparation of anti-FcεRI Ig comprises between 0.001 and 0.1 kU / L of anti-FcεRI IgE.

[0817] 290. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 284, in which the reduced IgG preparation of anti-FcεRI Ig comprises between 0.001 and 0.05 kU / L of anti-FcεRI IgE.

[0818] 291. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 284, in which the reduced IgG preparation of anti-FcεRI Ig comprises between 0.001 and 0.01 kU / L of anti-FcsRI IgE.

[0819] 292. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 291, wherein basophil activation after exposure to the reduced IgG anti-FcεRI Ig preparation is determined by determining the proportion of basophils expressing one or more selected markers from the group consisting of CD63, CD203c and their combinations.

[0820] 293. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 292, in which basophil activation after exposure to the reduced IgG anti-FcεRI Ig preparation is determined by Petition 870250100974, dated 04 / 11 / 2025, pp. 146 / 216 141 / 172 determination of the proportion of basophils expressing CD63.

[0821] 294. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 293, wherein basophil activation after exposure to the reduced IgG anti-FcεRI Ig preparation is determined by determining the proportion of basophils expressing CD203c.

[0822] 295. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 294, wherein basophil activation after exposure to the reduced IgG anti-FcεRI Ig preparation is determined by determining the proportion of basophils expressing CD63 and CD203c.

[0823] 296. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 293 and 295, in which the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0824] 297. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 293, 295 or 296, in which the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 1% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0825] 298. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 293, 295 or 296, in which the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 2% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0826] 299. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 293, 295 or 296, in which the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 3% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation. Petition 870250100974, dated 04 / 11 / 2025, pp. 147 / 216 142 / 172

[0827] 300. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 293, 295 or 296, in which the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 4% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0828] 301. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 293, 295 or 296, in which the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0829] 302. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 293, 295 to 301, wherein the basophil activation ratio is determined by incubating basophils with the reduced IgG anti-FcεRI Ig preparation and quantifying the proportion of CD63-expressing basophils in the total basophil population using flow cytometry.

[0830] 303. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 294 or 295, in which the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0831] 304. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 294, 295 or 303, in which the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 1% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0832] 305. The reduced IgG preparation of anti-FcεRI Ig from any of paragraphs 292, 294, 295 or 303, in which the proportion of basophils expressing CD203c after exposure to the reduced IgG preparation of Petition 870250100974, dated 04 / 11 / 2025, pp. 148 / 216 143 / 172 Anti-FcεRI IgG is less than 2% of the total basophil population exposed to the reduced anti-FcεRI IgG preparation.

[0833] 306. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 294, 295 or 303, in which the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 3% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0834] 307. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 294, 295 or 303, in which the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 4% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0835] 308. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 294, 295 or 303, in which the proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation.

[0836] 309. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 292, 294, 295 or 303, wherein the basophil activation ratio is determined by incubating basophils with the reduced IgG anti-FcεRI Ig preparation and quantifying the proportion of basophils expressing CD203c in the total basophil population using flow cytometry.

[0837] 310. The reduced IgG anti-FcεRI Ig preparation of any of paragraphs 258 to 291, wherein mast cell activation after exposure to the reduced IgG anti-FcεRI Ig preparation is determined by determining the proportion of mast cells expressing CD107a.

[0838] 311. Reduced IgG preparation of anti-FcεRI Ig of the paragraph 310, in which the proportion of mast cells expressing CD107a after exposure to the reduced IgG preparation of anti-FcεRI Ig is less than 1%, Petition 870250100974, dated 04 / 11 / 2025, pp. 149 / 216 144 / 172 less than 2%, less than 3%, less than 4%, or less than 5% of the total mast cell population exposed to the reduced IgG preparation of anti-FcεRI Ig.

[0839] 312. The reduced IgG anti-FcεRI Ig preparation of paragraphs 310 or 311, in which the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 1% of the total basophil population exposed to the reduced IgG anti-FcεRI Ig preparation.

[0840] 313. The reduced IgG anti-FcεRI Ig preparation of paragraphs 310 or 311, in which the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 2% of the total basophil population exposed to the reduced IgG anti-FcεRI Ig preparation.

[0841] 314. The reduced IgG anti-FcεRI Ig preparation of paragraphs 310 or 311, in which the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 3% of the total basophil population exposed to the reduced IgG anti-FcεRI Ig preparation.

[0842] 315. The reduced IgG anti-FcεRI Ig preparation of paragraphs 310 or 311, in which the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 4% of the total basophil population exposed to the reduced IgG anti-FcεRI Ig preparation.

[0843] 316. The reduced IgG anti-FcεRI Ig preparation of paragraphs 310 or 311, in which the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total basophil population exposed to the reduced IgG anti-FcεRI Ig preparation.

[0844] 317. The reduced IgG preparation of anti-FcεRI Ig from any of paragraphs 310 to 316, in which the mast cell activation ratio Petition 870250100974, dated 04 / 11 / 2025, pp. 150 / 216 The 145 / 172 ratio is determined by incubating mast cells with the reduced IgG preparation of anti-FcεRI Ig and by quantifying the proportion of mast cells expressing CD107a in the total mast cell population using flow cytometry.

[0845] 318. A pharmaceutical composition comprising the reduced preparation of Fc epsilon I antireceptor immunoglobulin (Ig) (FcεRI) produced by a method of any of paragraphs 174 to 257.

[0846] 319. A pharmaceutical composition comprising the preparation of reduced Fc epsilon I antireceptor immunoglobulin (Ig) IgG of any of paragraphs 258 to 317.

[0847] 320. A combined IgG preparation, wherein the combined IgG preparation comprises a detectable amount of an Fc epsilon I receptor immunoglobulin (Ig) (FcεRI).

[0848] 321. The combined IgG preparation of paragraph 320, wherein the detectable amount of anti-FcεRI Ig comprises more than 40 μg / mL, more than 45 μg / mL, more than 50 μg / mL, more than 55 μg / mL or more than 60 μg / mL of anti-FcεRI IgG.

[0849] 322. The combined IgG preparation of either paragraph 320 or 321, in which the detectable amount of anti-FcεRI Ig comprises more than 40 μg / mL of anti-FcεRI IgG.

[0850] 323. The combined IgG preparation of any of paragraphs 320 to 322, in which the detectable amount of anti-FcεRI Ig comprises more than 45 μg / mL of anti-FcεRI IgG.

[0851] 324. The combined IgG preparation of any of paragraphs 320 to 323, in which the detectable amount of anti-FcεRI Ig comprises more than 50 μg / mL of anti-FcεRI IgG.

[0852] 325. The combined IgG preparation of any of paragraphs 320 to 324, in which the detectable amount of anti-FcεRI Ig comprises more than 55 μg / mL of anti-FcεRI IgG.

[0853] 326. The combined IgG preparation of any of the Petition 870250100974, dated 04 / 11 / 2025, pp. 151 / 216 146 / 172 paragraphs 320 to 325, where the detectable amount of anti-FcεRI Ig comprises more than 60 μg / mL of anti-FcεRI IgG.

[0854] 327. A combined IgG preparation of any of paragraphs 320 to 326, in which the detectable amount of anti-FcεRI Ig comprises more than 0.1 kU / L, more than 0.5 kU / L, more than 1 kU / L or more than 1.5 kU / L of anti-FcεRI IgE.

[0855] 328. The combined IgG preparation of any of paragraphs 320 to 327, in which the detectable amount of anti-FcεRI Ig comprises more than 0.1 kU / L of anti-FcεRI IgE.

[0856] 329. The combined IgG preparation of any of paragraphs 320 to 328, in which the detectable amount of anti-FcεRI Ig comprises more than 0.5 kU / L of anti-FcεRI IgE.

[0857] 330. The combined IgG preparation of any of paragraphs 320 to 329, in which the detectable amount of anti-FcεRI Ig comprises more than 1 kU / L of anti-FcεRI IgE.

[0858] 331. The combined IgG preparation of any of paragraphs 320 to 330, in which the detectable amount of anti-FcεRI Ig comprises more than 1.5 kU / L of anti-FcεRI IgE.

[0859] 332. The combined IgG preparation of any of paragraphs 320 to 331, in which the detectable amount of anti-FcεRI Ig comprises between 0.1 and 5 kU / L of anti-FcεRI IgE.

[0860] 333. The combined IgG preparation of any of paragraphs 320 to 332, wherein basophil activation after exposure to the combined IgG preparation is determined by determining the proportion of basophils expressing one or more selected markers from the group consisting of CD63, CD203c and their combinations.

[0861] 334. The combined IgG preparation of any of paragraphs 320 to 333, wherein basophil activation after exposure to the combined IgG preparation is determined by determining the proportion of basophils expressing CD63. Petition 870250100974, dated 04 / 11 / 2025, pages 152 / 216 147 / 172

[0862] 335. The combined IgG preparation of any of paragraphs 320 to 333, wherein basophil activation after exposure to the combined IgG preparation is determined by determining the proportion of basophils expressing CD203c.

[0863] 336. The combined IgG preparation of any of paragraphs 320 to 333, wherein basophil activation after exposure to the combined IgG preparation is determined by determining the proportion of basophils expressing CD63 and CD203c.

[0864] 337. The combined IgG preparation of any of paragraphs 320 to 334 or 336, in which the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10% of the total population of basophils exposed to the combined IgG preparation.

[0865] 338. The combined IgG preparation of either paragraphs 320 to 334 or 336 to 337, in which the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is greater than 5% of the total population of basophils exposed to the combined IgG preparation.

[0866] 339. The combined IgG preparation of either paragraphs 320 to 334 or 336 to 338, in which the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is greater than 6% of the total population of basophils exposed to the combined IgG preparation.

[0867] 340. The combined IgG preparation of either paragraphs 320 to 334 or 336 to 339, in which the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is greater than 7% of the total population of basophils exposed to the combined IgG preparation.

[0868] 341. The combined IgG preparation of any of the Petition 870250100974, dated 04 / 11 / 2025, pp. 153 / 216 148 / 172 paragraphs 320 to 334 or 336 to 340, where the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is greater than 8% of the total population of basophils exposed to the combined IgG preparation.

[0869] 342. The combined IgG preparation of either paragraphs 320 to 334 or 336 to 341, in which the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is greater than 9% of the total population of basophils exposed to the combined IgG preparation.

[0870] 343. The combined IgG preparation of either paragraphs 320 to 334 or 336 to 342, in which the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is greater than 10% of the total population of basophils exposed to the combined IgG preparation.

[0871] 344. The method of either paragraphs 320 to 334 or 336 to 342, in which the basophil activation ratio is determined by incubating basophils with a plasma sample or fraction thereof and quantifying the proportion of CD63-expressing basophils in the total basophil population using flow cytometry.

[0872] 345. The combined IgG preparation of any of paragraphs 320 to 333 or 335, in which the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9% or greater than 10% of the total population of basophils exposed to the combined IgG preparation.

[0873] 346. The combined IgG preparation of any of paragraphs 320 to 333, 335 or 345, in which the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is greater than 5% of the total population of basophils exposed to the combined IgG preparation. Petition 870250100974, dated 04 / 11 / 2025, pp. 154 / 216 149 / 172

[0874] 347. The combined IgG preparation of any of paragraphs 320 to 333, 335 or 345 to 346, in which the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is greater than 6% of the total population of basophils exposed to the combined IgG preparation.

[0875] 348. The combined IgG preparation of any of paragraphs 320 to 333, 335 or 345 to 347, in which the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is greater than 7% of the total population of basophils exposed to the combined IgG preparation.

[0876] 349. The combined IgG preparation of any of paragraphs 320 to 333, 335 or 345 to 348, in which the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is greater than 8% of the total population of basophils exposed to the combined IgG preparation.

[0877] 350. The combined IgG preparation of any of paragraphs 320 to 333, 335 or 345 to 349, in which the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is greater than 9% of the total population of basophils exposed to the combined IgG preparation.

[0878] 351. The combined IgG preparation of any of paragraphs 320 to 333, 335 or 345 to 350, in which the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is greater than 10% of the total population of basophils exposed to the combined IgG preparation.

[0879] 352. The combined IgG preparation of any of paragraphs 320 to 333, 335 or 345 to 351, wherein the basophil activation ratio is determined by incubating basophils with the combined IgG preparation and quantifying the proportion of basophils expressing CD203c in the total basophil population using cytometry of Petition 870250100974, dated 04 / 11 / 2025, pages 155 / 216 150 / 172 flow.

[0880] 353. The combined IgG preparation of any of paragraphs 320 to 352, wherein mast cell activation after exposure to the combined IgG preparation is determined by determining the proportion of mast cells expressing CD107a in the total mast cell population exposed to the combined IgG preparation.

[0881] 354. The combined IgG preparation of paragraph 353, in which the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9% or greater than 10% of the total mast cell population exposed to the combined IgG preparation.

[0882] 355. The combined IgG preparation of paragraphs 353 or 354, in which the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is greater than 5% of the total mast cell population exposed to the combined IgG preparation.

[0883] 356. A combined IgG preparation of either paragraph 353 or 354, in which the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is greater than 6% of the total mast cell population exposed to the combined IgG preparation.

[0884] 357. A combined IgG preparation of either paragraph 353 or 354, in which the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is greater than 7% of the total mast cell population exposed to the combined IgG preparation.

[0885] 358. A combined IgG preparation of either paragraph 353 or 354, in which the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is greater than 8% of the total mast cell population exposed to the combined IgG preparation.

[0886] 359.The combined IgG preparation from either paragraph 353 or 354, in which the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is greater than 9%. Petition 870250100974, dated 04 / 11 / 2025, pages 156 / 216 151 / 172 of the total mast cell population exposed to the combined IgG preparation.

[0887] 360. The combined IgG preparation of either paragraph 353 or 354, in which the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is greater than 10% of the total mast cell population exposed to the combined IgG preparation.

[0888] 361. The combined IgG preparation of either paragraph 353 to 360, in which the proportion of mast cell activation is determined by incubating mast cells with the combined IgG preparation and quantifying the proportion of mast cells expressing CD107a in the total mast cell population using flow cytometry.

[0889] 362. A method for treating, preventing and / or delaying the progression of a condition in an individual, the method comprising administering the pharmaceutical composition of paragraphs 318 or 319 or the reduced IgG preparation of anti-FcεRI Ig of any of paragraphs 320 to 361.

[0890] 363. The pharmaceutical composition of paragraphs 318 or 319 or the reduced IgG preparation of anti-FcεRI Ig of any of paragraphs 320 to 361 for use in the treatment, prevention and / or retardation of the progression of a condition in an individual.

[0891] 364. Use of the pharmaceutical composition of paragraphs 318 or 319 or of the reduced IgG preparation of anti-FcεRI Ig of any of paragraphs 320 to 361 in the manufacture of a medicament to treat, prevent and / or delay the progression of a condition in an individual.

[0892] 365. The method of paragraph 362, or the pharmaceutical composition or preparation of reduced anti-FcεRI IgG of paragraph 363, or the use of paragraph 364, where the condition is related to an immunodeficiency, an inflammatory disease, an autoimmune disease or an acute infection.

[0893] 366. The method or pharmaceutical composition or preparation of reduced IgG anti-FcεRI Ig or the use of paragraph 365, wherein the Petition 870250100974, dated 04 / 11 / 2025, pp. 157 / 216 152 / 172 Immunodeficiency is selected from the group consisting of congenital agammaglobulinemia, congenital hypogammaglobulinemia, common variable immunodeficiency, severe combined immunodeficiency, allogeneic bone marrow transplantation, chronic lymphocytic leukemia, pediatric HIV, kidney transplantation with a recipient with a high antibody index or with an ABO-incompatible donor, chronic fatigue syndrome, Clostridium difficile colitis, Graves' ophthalmopathy, inclusion body myositis muscular dystrophy, Lambert-Eaton syndrome, lupus erythematosus, multifocal motor neuropathy, myasthenia gravis, neonatal alloimmune thrombocytopenia, parvovirus B19 infection, pemphigus, post-transfusion purpura, renal transplant rejection, spontaneous abortion, stiff-person syndrome, opsoclonus, myoclonus, severe sepsis and septic shock in critically ill adults, necrolysis toxic epidermal leukemia, chronic lymphocytic leukemia, multiple myeloma, X-linked agammaglobulinemia, hypogammaglobulinemia,Recurrent mitral valve disease (RRMS), IgG subclass deficiencies with recurrent infections, and combinations thereof.

[0894] 367. The method or pharmaceutical composition or preparation of reduced anti-FcεRI IgG or the use of paragraph 365, wherein the inflammatory or autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), antiphospholipid syndrome, immune thrombocytopenia (ITP), Kawasaki disease, Guillain-Barré syndrome (GBS), multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), myasthenia gravis (MG), skin blistering diseases, scleroderma, dermatomyositis, polymyositis, Alzheimer's disease, Parkinson's disease, Down syndrome-related Alzheimer's disease, cerebral amyloid angiopathy, dementia with Lewy bodies, frontotemporal lobar degeneration, vascular dementia, cell and organ transplantation and combinations thereof.

[0895] 368. A method for preparing an immunoglobulin (Ig) preparation from a plasma sample or fraction thereof. Petition 870250100974, dated 04 / 11 / 2025, pp. 158 / 216 153 / 172 of it, the Ig preparation that reduced adverse reactions in an individual, the method that includes determining the ratio of basophil and / or mast cell activation after exposure to a plasma sample or fraction thereof;

[0896] (i) including the sample or plasma fraction in the Ig preparation if the proportion of basophils expressing CD63 after exposure to the sample or plasma fraction is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total population of basophils exposed to the sample or plasma fraction;

[0897] (ii) excluding the sample or plasma fraction from the Ig preparation if the proportion of basophils expressing CD63 after exposure to the sample or plasma fraction is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14% or greater than 15% of the total population of basophils exposed to the sample or plasma fraction;

[0898] (iii) including the sample or plasma fraction in the Ig preparation if the proportion of basophils expressing CD203c after exposure to the sample or plasma fraction is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total population of basophils exposed to the sample or plasma fraction;

[0899] (iv) excluding the sample or plasma fraction from the Ig preparation if the proportion of basophils expressing CD203c after exposure to the sample or plasma fraction is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14% or greater than 15% of the total population of basophils exposed to the sample or plasma fraction;

[0900] (v) including the sample or plasma fraction in the Ig preparation if the proportion of mast cells expressing CD107a after exposure to the sample or plasma fraction is less than 1%, less than 2%, less than 3%, less than 4% or less than 5% of the total mast cell population exposed to the sample or plasma fraction; Petition 870250100974, dated 04 / 11 / 2025, pp. 159 / 216 154 / 172

[0901] (vi) excluding the sample or plasma fraction from the Ig preparation if the proportion of mast cells expressing CD107a after exposure to the sample or plasma fraction is greater than 5%, greater than 6%, greater than 7%, greater than 8%, greater than 9%, greater than 10%, greater than 11%, greater than 12%, greater than 13%, greater than 14% or greater than 15% of the total mast cell population exposed to the sample or plasma fraction; and / or

[0902] (v) inclusion of the plasma sample or fraction thereof in the preparation of Ig if the plasma sample or fraction thereof contains less than a detectable amount of adverse-reaction-causing Ig, wherein the detectable amount of adverse-reaction-causing Ig is less than 40 μg / mL, less than 35 μg / mL, less than 30 μg / mL, less than 25 μg / mL, less than 20 μg / mL, less than 15 μg / mL, less than 10 μg / mL or less than 5 μg / mL.

[0903] 369. The method of paragraph 368, where the adverse reaction is a hypersensitivity reaction (HSR).

[0904] 370. The method of paragraph 369, in which HSR is selected from the group consisting of pruritus, erythema, urticaria, swelling and their combinations.

[0905] 371. The method described in any of paragraphs 368 to 370, where the adverse reaction occurs at the infusion site, during the infusion, shortly after the infusion, or in combinations of these situations.

[0906] The present invention includes the following non-limiting examples. EXAMPLES EXAMPLE 1: DONOR SIMILARITY ANALYSIS: DATA-DRIVEN INVESTIGATION OF DONOR Z

[0907] A series of adverse event reports related to hypersensitivity reactions (HSR-AE) have become known for certain batches of SCIG products. As the signs of hypersensitivity received for these IgG batches had similar characteristics, an investigation was initiated. Petition 870250100974, dated 04 / 11 / 2025, pp. 160 / 216 155 / 172 data-driven investigation with a specific focus on determining whether there was a plasma donor introducing a biochemical signal into the finished product that could trigger hypersensitivity-related reactions (HSR-AE) in patients. This donor will be referred to as "Donor Z" hereafter, and the data-driven investigation will be called the "Donor Z investigation." METHODOLOGY APPROACH

[0908] Donor Z was presumed to be the sole cause of the observed HSR-AEs and that most or all of Donor Z’s donations led to HSR-AE reports for the respective IgG batches. With these solid assumptions, it was clear that Donor Z must have contributed to all batches withdrawn. Thus, only one donor who contributed to all affected batches (a “common donor”) was sought.

[0909] In the initial stage of the first four batches withdrawn, but also in 5, 6 or more batches withdrawn, hundreds of donors were still common donors and additional insights were needed to identify donor Z. To solve this problem, the following considerations and implications were postulated.

[0910] Based on the assumption of exactly one donor Z, all other ordinary donors were understood to be ordinary donors by chance, in the sense that their donations ended up in the same finished products (FPs) as donor Z by chance.

[0911] 1. The pro...

Claims

1. A method for detecting an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI) in a plasma sample or a fraction thereof, characterized in that it comprises: (i) contacting the sample with a ligand that binds to the anti-FcεRI Ig in the sample to form a complex; and (ii) detecting the complex, the presence of the complex being indicative of the presence of anti-FcεRI Ig in the plasma sample or a fraction thereof.

2. A method according to claim 1, characterized in that anti-FcεRI Ig binds to an FcεRI epitope and activates an FcεRI-mediated signaling pathway.

3. A method according to claim 1 or 2, characterized in that anti-FcεRI Ig binds to an α chain of FcεRI and activates an FcεRI-mediated signaling pathway.

4. A method, according to any one of claims 1 to 3, characterized in that activation of the FcεRI-mediated signaling pathway induces activation and / or degranulation of basophils and / or mast cells.

5. Method, according to any one of claims 1 to 4, characterized in that the anti-FcεRI Ig is an anti-FcεRI IgG and / or an anti-FcεRI IgE.

6. A method according to any one of claims 1 to 5, characterized in that the ligand comprises an FcεRI or a fragment or epitope thereof.

7. A method, according to any one of claims 1 to 6, characterized in that the detection protein comprises a variable antibody region that binds to anti-FcεRI Ig.

8. Method, according to any one of claims 1 to 7, characterized in that it further comprises determining the level of anti-FcεRI Ig in the sample or plasma fraction thereof. Petition 870250100974, dated 04 / 11 / 2025, p. 179 / 216 2 / 7 9. Method, according to claim 8, characterized in that the anti-FcεRI IgG in the sample or plasma fraction thereof is present in a detectable quantity, wherein the detectable quantity of anti-FcεRI Ig is at least 40 μg / mL.

10. Method, according to claim 8 or 9, characterized in that the anti-FcεRI IgE in the sample or plasma fraction thereof is present in a detectable quantity, wherein the detectable quantity of anti-FcεRI IgE is at least 0.1 kU / L.

11. Method, according to any one of claims 1 to 10, characterized in that it further comprises determining the proportion of basophil and / or mast cell activation induced by the sample or plasma fraction thereof.

12. Method, according to claim 11, characterized in that the activation ratio of basophils and / or mast cells after exposure to the sample or plasma fraction thereof is determined by determining the proportion of basophils and / or mast cells expressing one or more selected markers from the group consisting of CD63, CD203c, CD107a and combinations thereof.

13. Method according to claim 12, characterized in that the proportion of basophils expressing CD63 after exposure to the sample or plasma fraction is greater than 5% of the total population of basophils exposed to the sample or plasma fraction thereof.

14. Method, according to claim 12 or 13, characterized in that the proportion of basophils expressing CD203c after exposure to the sample or plasma fraction is greater than 5% of the total population of basophils exposed to the sample or plasma fraction thereof.

15. Method, according to any one of claims 12 to 14, characterized in that the proportion of mast cells expressing CD107a after exposure to the sample or plasma fraction thereof is Petition 870250100974, dated 04 / 11 / 2025, page 180 / 216 3 / 7 greater than 5% of the total population of mast cells exposed to the sample or plasma fraction thereof.

16. A method according to any one of claims 1 to 15, characterized in that the plasma sample or fraction is selected from the group consisting of a human blood plasma sample, an IgG intermediate product, intravenous immunoglobulin G (IVIG), subcutaneous immunoglobulin G (SCIG), cryo-rich plasma, cryo-poor plasma, a Supernatant I (SN I), a Cohn Fraction II (Fr II), a Cohn Fraction II+III (Fr II+III), a Cohn Fraction I+II+III (FrI+II+III), a Kistler / Nitschmann Precipitate A (KN A), a Kistler / Nitschmann Precipitate B (KN B), a Kistler / Nitschmann Precipitate B from the Supernatant (KN B+1), and combinations thereof.

17. A method, according to any one of claims 1 to 16, characterized in that the sample or plasma fraction is a sample or fraction of human blood plasma from one or more individuals.

18. Method, according to any one of claims 1 to 17, characterized in that it further comprises administering the sample or plasma fraction thereof to an individual if anti-FcεRI Ig is not present in a detectable quantity.

19. Method, according to any one of claims 1 to 18, characterized in that it further comprises including the sample or plasma fraction thereof in a combined blood plasma sample if anti-FcεRI Ig is not present in a detectable quantity.

20. Method, according to any one of claims 1 to 19, characterized in that it further comprises excluding the sample or plasma fraction thereof from a pooled blood plasma sample if anti-FcεRI Ig is present in a detectable quantity.

21. Method for preparing a reduced preparation of anti-Fc epsilon I receptor immunoglobulin (Ig) from a plasma sample or a fraction thereof, characterized in that it comprises: (i) loading the sample or a plasma fraction thereof onto an affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig in the plasma sample or its fraction immobilized on an affinity chromatography resin matrix; and (ii) collecting a reduced preparation of anti-FcεRI Ig.

22. Method according to claim 21, characterized in that it further comprises detecting the level of anti-FcεRI Ig in the sample or plasma fraction thereof, performing the method as defined in any one of claims 1 to 24.

23. A method according to claim 21 or 22, characterized in that the reduced anti-FcεRI Ig preparation induces reduced activation of an FcεRI-mediated signaling pathway compared to a preparation in which the anti-FcεRI Ig is not reduced.

24. Method, according to any one of claims 21 to 23, characterized in that the reduced anti-FcεRI Ig preparation induces a reduction in basophil and / or mast cell activation compared to a preparation in which the anti-FcεRI Ig is not reduced.

25. Method according to claim 24, characterized in that the proportion of basophils expressing CD63 after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation, and / or the proportion of basophils expressing CD203c after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced anti-FcεRI Ig preparation, and / or the proportion of mast cells expressing CD107a after exposure to the reduced anti-FcεRI Ig preparation is less than 5% of the total population of mast cells exposed to the reduced anti-FcεRI Ig preparation. Petition 870250100974, dated 04 / 11 / 2025, p. 182 / 216 5 / 7 26. Method, according to any one of claims 21 to 25, characterized in that the reduced anti-FcεRI Ig preparation comprises less than 40 μg / mL of anti-FcεRI IgG and / or less than 0.1 kU / L of anti-FcεRI IgE.

27. Method according to any one of claims 21 to 26, characterized in that affinity chromatography is continuous affinity chromatography comprising: (i) a first affinity chromatography resin comprising a ligand that binds to anti-FcεRI Ig in the sample or plasma fraction immobilized on a matrix of the first affinity chromatography resin; and (ii) a second affinity chromatography resin comprising a blood group A antigen and / or a blood group B antigen immobilized on a matrix of the second affinity chromatography resin.

28. Pharmaceutical composition, characterized in that it comprises a reduced preparation of Fc epsilon I antireceptor immunoglobulin (Ig) (FcεRI) produced by a method as defined in any one of claims 21 to 27.

29. Preparation of reduced IgG of anti-Fc epsilon I immunoglobulin (Ig) (FcεRI), characterized in that it comprises polyclonal IgG.

30. Reduced IgG preparation of anti-FcεRI Ig, according to claim 29, characterized in that it comprises less than 40 μg / mL of anti-FcεRI IgG and / or less than 0.1 kU / L of anti-FcεRI IgE.

31. Reduced IgG anti-FcεRI Ig preparation, according to any one of claims 29 to 30, characterized in that the proportion of basophils expressing CD63 after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation, and / or Petition 870250100974, dated 04 / 11 / 2025, p. 183 / 216 6 / 7 The proportion of basophils expressing CD203c after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of basophils exposed to the reduced IgG anti-FcεRI Ig preparation and / or the proportion of mast cells expressing CD107a after exposure to the reduced IgG anti-FcεRI Ig preparation is less than 5% of the total population of mast cells exposed to the reduced IgG anti-FcεRI Ig preparation.

32. Combined IgG preparation, characterized in that the combined IgG preparation comprises a detectable amount of an anti-Fc epsilon I receptor immunoglobulin (Ig) (FcεRI).

33. Combined IgG preparation, according to claim 32, characterized in that the proportion of basophils expressing CD63 after exposure to the combined IgG preparation is less than 5% of the total population of basophils exposed to the combined IgG preparation, and / or the proportion of basophils expressing CD203c after exposure to the combined IgG preparation is less than 5% of the total population of basophils exposed to the combined IgG preparation, and / or the proportion of mast cells expressing CD107a after exposure to the combined IgG preparation is less than 5% of the total population of mast cells exposed to the combined IgG preparation.

34. A method for treating, preventing and / or delaying the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease or an acute infection in an individual, characterized in that it comprises administering the pharmaceutical composition, as defined in claim 28, or the reduced IgG preparation of anti-FcεRI Ig, as defined in any of claims 29 to 31.

35. Pharmaceutical composition, according to claim 28, or reduced IgG preparation of anti-FcεRI Ig, according to any of claims 29 to 31, characterized in that it is for use in the treatment, prevention and / or delaying of the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease or an acute infection in an individual.

36. Use of the pharmaceutical composition, as defined in claim 28, or of the reduced IgG preparation of anti-FcεRI Ig, as defined in any of claims 29 to 31, characterized in that it is for treating, preventing and / or delaying the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease or an acute infection in an individual.

37. Use of the pharmaceutical composition, as defined in claim 28, or of the reduced IgG preparation of anti-FcεRI Ig, as defined in any of claims 29 to 31, characterized in that it is in the manufacture of a medicament to treat, prevent and / or delay the progression of a condition related to an immunodeficiency, an inflammatory disease, an autoimmune disease or an acute infection in an individual.

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