Composition and method for treating androgen-dependent disorders

Patent metadata

Field	Value
Publication number	US-10240132-B2
Application number	US-201715471194-A
Country	US
Kind code	B2
Filing date	Mar 28, 2017
Priority date	Mar 28, 2016
Publication date	Mar 26, 2019
Grant date	Mar 26, 2019

Abstract

Chimeric polypeptides comprising a dihydrotestosterone (DHT) reductase moiety, such as 3 alpha-hydroxysteroid dehydrogenase (3α-HSD), fused to a signal peptide moiety, polynucleotides encoding same, and compositions comprising at least one microorganism cell capable of secreting the chimeric polypeptide, are provided. Further provided are methods and kits for treating, preventing or ameliorating androgen-dependent disorders, including but not limited to androgenic alopecia.

First claim

The invention claimed is:

1. A polynucleotide molecule encoding a chimeric polypeptide comprising a first moiety and a second moiety, said first moiety is a dihydrotestosterone (DHT) reductase and said second moiety is a bacterial signal peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 16-45 or an analog thereof having at least 85% sequence identity thereto.

2. A composition comprising a first microorganism cell comprising a first polynucleotide molecule of claim 1 , and any one of:
(i) a DHT reductase cofactor;
(ii) a second polynucleotide molecule encoding a DHT reductase cofactor producing enzyme, within said first microorganism cell; and
(iii) a second microorganism cell, wherein said second microorganism cell comprises a second polynucleotide molecule encoding a DHT reductase cofactor producing enzyme.

3. The composition of claim 2 , wherein the first microorganism cell is capable of expressing and secreting said chimeric polypeptide.

4. The composition of claim 3 , wherein said DHT reductase cofactor is selected from NADPH and NADH.

5. The composition of claim 3 , wherein said DHT reductase cofactor producing enzyme is Glucose-6-phosphate 1-dehydrogenase (Zwf).

6. The composition of claim 2 , wherein said first microorganism cell is selected from the group consisting of: Bacillus, Staphylococcus, Actinobacteria, Firmicutes, Proteobacteria, Bacteroidetes, Propionibacteria, Corynebacteria, Flavobacteria, lactobacillus, Escherichia coli, bifidobacteria, bacteroides , and Brevibacterium linens.

7. The composition of claim 2 , wherein said first microorganism cell is a Bacillus bacterium.

8. A kit for treating an androgen-dependent disorder, the kit comprising a first composition comprising a first microorganism cell, said first microorganism cell comprises a first polynucleotide sequence encoding a chimeric polypeptide comprising a first moiety and a second moiety, said first moiety is a dihydrotestosterone (DHT) reductase and said second moiety is a bacterial signal peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 16-45 or an analog thereof having at least 85% sequence identity thereto, and a second composition comprising any one of:
(i) a DHT reductase cofactor; and
(ii) a second microorganism cell, wherein said second microorganism cell comprises a second polynucleotide molecule encoding a DHT reductase cofactor producing enzyme.

9. The kit of claim 8 , wherein said DHT reductase is 3 alpha HSD (3α-HSD) or an analog thereof.

10. A method for treating or ameliorating an androgen-dependent disorder in a subject in need thereof, the method comprising administering a first composition comprising a first microorganism cell, said first microorganism cell comprises a first polynucleotide molecule of claim 1 , thereby treating or ameliorating an androgen-dependent disorder in said subject.

11. The method of claim 10 , wherein said DHT reductase is 3 alpha HSD (3α-HSD) or a homolog thereof.

12. The method of claim 10 , further comprising administering to the subject and a second composition, said second composition being selected from (i) a composition comprising a DHT reductase cofactor; and (ii) a composition comprising a second microorganism cell, said second microorganism cell comprises a second polynucleotide encoding a DHT reductase cofactor producing enzyme.

13. The method of claim 10 , wherein said androgen-dependent disorder is androgenic alopecia.

14. The method of claim 10 , wherein said administering is topically applying to the scalp of said subject.

Assignees

• Technion Res & Dev Foundation

Inventors

• Amit Roee
• Tomsov Alexey
• Atar Orna
• Abrahami Liron
• ANNIS Yael
• Cohen Roni
• ERESKOVSKY Alexandra
• Katz Noa
• Levy Lior
• Lufton Maayan
• OFEK Tal
• Sheinkman Sagi
• SHMUEL Nitzan
• Vaknin Inbal
• VEKSLER Ruth
• Yannai Adi

Classifications

• C12Y101/01225

  Chlordecone reductase (1.1.1.225) · CPC title

• A61K38/443

  acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1) · CPC title

• C07K19/00

  Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K9/0014

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title