Therapeutic treatment of skin disease with recombinant commensal skin microorganisms

Inventors

Munivar, Azim MominWhitfill, Travis Michael

Assignees

Azitra Inc

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Publication Number

US-12036248-B2

Patent

Publication Date

2024-07-16

Expiration Date


Abstract

The invention relates to methods for treating or preventing abnormal skin conditions in a human in need thereof, comprising administering a cell culture composition comprising a living culture of bacteria comprising at least one engineered strain that produces a recombinant polypeptide for therapeutic treatment of the abnormal skin condition. The invention also relates to pharmaceutical compositions containing, as the active principle, engineered microorganisms expressing non-vaccinogenic pharmacologically active recombinant therapeutic polypeptides in order to treat or prevent abnormal skin conditions.

Core Innovation

The invention relates to a method of treating or preventing eczema in a human in need thereof by administering a living cell culture composition that includes at least one engineered bacterial strain. The engineered bacterial strain is selected from Bifidobacterium, Brevibacterium, Propionibacterium, Lactococcus, Streptococcus, Staphylococcus, Lactobacillus, Enterococcus, Pediococcus, Leuconostoc, or Oenococcus, and mixtures thereof, and produces a therapeutically effective amount of a recombinant polypeptide for treating or preventing eczema.

The recombinant polypeptide comprises a filaggrin amino acid sequence, a secretion signal, and a cell penetrating peptide. The partial content further describes engineered skin-disease treatment and prevention using engineered commensal skin bacteria that continuously secrete non-vaccinogenic recombinant therapeutic polypeptides, including recombinant filaggrin therapeutically for eczema and atopic dermatitis.

The partial content also describes additional scope for filaggrin sequence selection and sequence similarity constraints relative to SEQ ID NO 1, including homology thresholds. The documented work described includes engineered Staphylococcus epidermidis expressing filaggrin (pAZT-01) and colonizing mouse skin, with recombinant filaggrin expression evidence, and related observations directed to mitigation of an atopic dermatitis phenotype.

Claims Coverage

The independent claim covers treating or preventing eczema in a human via administering a living cell culture composition containing engineered bacterial strains that produce a recombinant polypeptide with three defined components, yielding a therapeutically effective amount for eczema treatment or prevention.

Living cell culture composition for eczema treatment or prevention

A method of treating or preventing eczema in a human, comprising administering a living cell culture composition comprising at least one engineered bacterial strain selected from Bifidobacterium, Brevibacterium, Propionibacterium, Lactococcus, Streptococcus, Staphylococcus, Lactobacillus, Enterococcus, Pediococcus, Leuconostoc, or Oenococcus, or mixtures thereof.

Recombinant filaggrin polypeptide with secretion signal and cell penetrating peptide

The engineered bacterial strain produces a therapeutically effective amount of a recombinant polypeptide comprising a filaggrin amino acid sequence, a secretion signal, and a cell penetrating peptide, for treating or preventing eczema.

Specified filaggrin amino acid sequence via SEQ ID NO selections

The method further specifies that the filaggrin amino acid sequence comprises one or more specified SEQ ID NO sequences.

Filaggrin sequence homology to SEQ ID NO 1

The filaggrin amino acid sequence is defined to have at least specified levels of homology to SEQ ID NO 1.

Eczema severity or type specification

The method further specifies that the eczema treated is mild, moderate, severe, or hand eczema.

Overall claim coverage is centered on administering a living culture of engineered bacterial strains that continuously produce a recombinant polypeptide containing a filaggrin amino acid sequence together with a secretion signal and a cell penetrating peptide, with further narrowing by selecting specific filaggrin SEQ ID NOs, imposing homology thresholds to SEQ ID NO 1, and specifying eczema severity or type.

Stated Advantages

Not explicitly described in patent.

Documented Applications

Not explicitly described in patent.

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