Composition comprising probiotics and polypeptide having binding affinity for IgE and use thereof
Inventors
Jang, Myoung Ho • Sung, Young Chul • YANG, Zungyoon
Assignees
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Publication Number
US-12128076-B2
Publication Date
2024-10-29
Expiration Date
Abstract
A composition containing, as active ingredients, probiotics and a polypeptide with a binding ability to IgE is disclosed. In particular, a synergistic effect of remarkably decreasing food allergy was identified at the time of combined administration of probiotics and a recombinant protein containing an extracellular domain of an alpha subunit of an IgE Fc receptor. Therefore, it is expected that the composition is highly industrially applicable due to being able to exhibit a remarkable therapeutic effect on an IgE-mediated allergic disease as compared with conventional pharmaceutical compositions.
Core Innovation
The invention relates to treating or preventing an allergic disease of a subject by administering a probiotic and a specific IgE-binding polypeptide dimer. The probiotic is Bifidobacterium longum, and the polypeptide dimer comprises two monomers, each of which includes an extracellular domain of the alpha subunit of an IgE Fc receptor (FcεRIαECD) together with a modified Fc region.
The two monomers are linked via a hinge sequence corresponding to SEQ ID NO: 17 or SEQ ID NO: 18, with defined substitutions at Xaa1 to Xaa4, where Xaa1 and Xaa3 are Gly and Xaa2 and Xaa4 are Gly or Ser. The polypeptide dimer design combines FcεRIαECD with a modified Fc region through the hinge sequence.
The disclosed approach is directed to an allergy treatment context and is associated with an in vivo mouse food-allergy model showing a decrease in diarrhea and mast-cell activation/degranulation. The combination therapy is reported to reduce free IgE, lower mast-cell numbers, suppress goblet-cell hyperplasia, and decrease IL-33/Th2-associated signals.
The document further characterizes the polypeptide dimer as having a safety risk profile improved versus omalizumab by lacking FcγR/C1q binding and by increasing IgE affinity/persistence. Formulations and administration formats are described, including pharmaceutical composition, health functional food forms, and a kit with separate components, as well as oral versus parenteral administration routes for the probiotic and the polypeptide dimer.
Claims Coverage
The independent claim set out 2 administered components and specifies the biomolecular structure of the polypeptide dimer via FcεRIαECD, a modified Fc region, and a hinge sequence defined by SEQ ID NO: 17 or SEQ ID NO: 18 with defined residue constraints.
Treating or preventing an allergic disease with Bifidobacterium longum and an FcεRIαECD-modified Fc polypeptide dimer
A method for treating or preventing an allergic disease comprising administering a probiotic and administering a polypeptide dimer, wherein the probiotic is Bifidobacterium longum and the polypeptide dimer comprises two monomers, each of which comprises an extracellular domain of an alpha subunit of an IgE Fc receptor (FcεRIαECD) and each of which comprises a modified Fc region linked via a hinge.
Hinge-linked SEQ ID NO: 17 or SEQ ID NO: 18 polypeptide dimer architecture
The modified Fc region and the FcεRIαECD are linked via a hinge, wherein the hinge is Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa1 Xaa2 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 17) or Ala Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa3 Xaa4 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 18), with Xaa1 and Xaa3 being Gly and Xaa2 and Xaa4 being Gly or Ser.
Overall, the claim coverage centers on administering Bifidobacterium longum together with a two-monomer polypeptide dimer that combines FcεRIαECD with a modified Fc region, where the structural linkage is defined by a hinge sequence corresponding to SEQ ID NO: 17 or SEQ ID NO: 18 with specified residue constraints.
Stated Advantages
Reported in vivo efficacy in a mouse food-allergy model, including marked decreases in diarrhea and mast-cell activation/degranulation.
Reductions in free IgE, decreases in mast-cell numbers, suppression of goblet-cell hyperplasia, and decreased IL-33/Th2-associated signals.
Improved safety risk profile versus omalizumab by lacking FcγR/C1q binding.
Increased IgE affinity/persistence.
Documented Applications
Treating or preventing an allergic disease in a subject, including an in vivo mouse food-allergy model.
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