Composition for the treatment of antibody deficiencies

Patent metadata

Field	Value
Publication number	US-2021395348-A1
Application number	US-201917288013-A
Country	US
Kind code	A1
Filing date	Oct 29, 2019
Priority date	Oct 29, 2018
Publication date	Dec 23, 2021
Grant date	—

Abstract

The invention is in the field of therapy of antibody deficiencies. Inventors demonstrate for the first time in both controls and IgA-deficient patients, systemic anti-microbiota IgG responses correlate with reduced inflammation suggesting that systemic IgG responses contribute to the gut microbiota confinement. Furthermore, SIgAd-associated inflammation is inversely correlated with systemic anti-commensal IgG responses, which may thus serve as a second line of defense. Altogether, these data suggest that systemic IgG and intestinal IgA cooperate in different body compartments to limit systemic pro-inflammatory pathways. As selective IgA deficient patients harbour elevated seric anti-commensal IgG levels, these findings suggest that in selective IgA deficiency, microbiota confinement is obtained at the price of a strong inflammatory response. Accordingly, the invention relates to a composition containing immunoglobulins A (IgA), more particularly secretory IgA, for use by oral administration in the prevention or treatment of antibody deficiencies such as SIgAd (Selective IgA deficiency) or common variable immunodeficiency (CVID) and associated inflammatory diseases.

First claim

1 . A method of treating an antibody deficiency and/or an associated inflammatory disease in a subject in need thereof, comprising
administering to the subject a composition comprising IgA (immunoglobulins A) wherein the composition is administered orally, and wherein the antibody deficiency is a primary antibody deficiency that is SIgAd (Selective IgA deficiency) or common variable immunodeficiency (CVID); or a secondary antibody deficiency that is myeloma, Chronic Lymphocitic Leukemia (CLL), or an immune deficiency induced by a medical treatment.

2 . The method according to claim 1 , wherein the IgA are monoclonal IgA.

3 . The method according to claim 1 , wherein the IgA are secretory IgA.

4 . The method according to claim 1 , wherein the IgA are cross-reactive and bind to multiple bacterial targets.

5 . The method according to claim 1 , wherein said primary antibody deficiency is SIgAd (Selective IgA deficiency).

6 . The method according to claim 1 , wherein said primary antibody deficiency is common variable immunodeficiency (CVID).

7 . The method according to claim 1 , wherein the immune deficiency induced by a medical treatment is an antibody deficiency induced by immunosuppressive drugs or cytostatic drugs.

8 . The method according to claim 1 , wherein said inflammatory associated disease is selected from the group consisting of sepsis, autoimmune disease and/or malabsorption due to inflammatory gut disease).

9 . The method of claim 8 , wherein the inflammatory gut disease is IBD.

Assignees

• Inst Nat Sante Rech Med
• Univ Sorbonne
• Assist Publique Hopitaux Paris Aphp

Inventors

• Gorochov Guy
• Larsen Martin
• Sterlin Delphine
• Fadlallah Jehane

Classifications

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K16/1271 Primary

  Micrococcaceae (F); Staphylococcaceae (F), e.g. Staphylococcus (G) · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title