IP Library › Granted Patent US 12,263,208
Granted Patent B2
US 12,263,208 · App. 18/882,318 · Granted Apr 1, 2025

Recombinant cell wall hydrolases

Inventors: Teresa Shock (San Francisco, CA); Oliver Liu (San Francisco, CA); Maritza Miller (Oakland, CA); Jennifer Shock (San Francisco, CA)
Assignee: Topaz Biosciences, Inc.
A61K38/482A61K9/06A61P17/00C12N9/50
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Quick Facts
Patent No.
US 12,263,208
App. No.
18/882,318
Granted
Apr 1, 2025
Kind
B2
Abstract

The present disclosure relates to novel chimeric cell wall hydrolases with anti- Staphylococcus activity. The disclosure also relates to compositions comprising these chimeric cell wall hydrolases and uses thereof in the treatment of conditions associated with Staphylococcus sp.

Claims (31)

1. A recombinant cell wall hydrolase (CWH) comprising:

a) an enzymatically active domain (EAD) from LysSA12; and

b) a cell wall binding domain (CBD) from PlySs2.

2. The recombinant CWH of claim 1 , wherein the EAD has at least 90% sequence identity with the sequence of SEQ ID NO: 11.

3. The recombinant CWH of claim 1 , wherein the CBD has at least 90% sequence identity with the sequence of SEQ ID NO: 17.

4. The recombinant CWH of claim 1 , wherein the EAD comprises the sequence of SEQ ID NO: 11.

5. The recombinant CWH of claim 1 , wherein the CBD comprises the sequence of SEQ ID NO: 17.

6. The recombinant CWH of claim 1 , wherein the recombinant CWH has at least 80% sequence identity with the sequence of SEQ ID NO: 21.

7. The recombinant CWH of claim 1 , wherein the recombinant CWH comprises the sequence of SEQ ID NO: 21.

8. The recombinant CWH of claim 1 , wherein the recombinant CWH is active against a species of Staphylococcus.

9. The recombinant CWH of claim 8 , wherein the recombinant CWH has a minimum inhibitory concentration (MIC) of less than or equal to 50 μg/mL against a species of Staphylococcus.

10. The recombinant CWH of claim 8 , wherein the recombinant CWH has a minimum inhibitory concentration (MIC) of less than or equal to 10 μg/mL against a species of Staphylococcus.

11. The recombinant CWH of claim 8 , wherein the species is Staphylococcus aureus.

12. The recombinant CWH of claim 8 , wherein the recombinant CWH demonstrates selective activity against Staphylococcus aureus over Staphylococcus epidermidis.

13. The recombinant CWH of claim 12 , wherein the recombinant CWH has at least 2-fold selectivity for Staphylococcus aureus over Staphylococcus epidermidis.

14. The recombinant CWH of claim 12 , wherein the recombinant CWH has at least 10-fold selectivity for Staphylococcus aureus over Staphylococcus epidermidis.

15. The recombinant CWH of claim 8 , wherein the recombinant CWH retains its anti- Staphylococcus activity after being exposed to a temperature up to 45° C.

16. The recombinant CWH of claim 8 , wherein the recombinant CWH retains its anti- Staphylococcus activity after being exposed to a temperature up to 50° C.

17. The recombinant CWH of claim 8 , wherein the recombinant CWH is active within a pH range of pH 6-8.

18. The recombinant CWH of claim 8 , wherein the recombinant CWH is active within a pH range of pH 5-8.

19. A topical formulation comprising the recombinant CWH according to claim 1 .

20. The formulation of claim 19 , wherein the formulation is a hydrogel.

21. The formulation of claim 19 , wherein the formulation comprises 1-10 μg/mL of the recombinant CWH.

22. The formulation of claim 19 , wherein the formulation comprises 0.5-10% w/v of a humectant selected from the list consisting of: aloe vera, betaine, butylene glycol, caprylyl glycol, dimethicone, fructose, glucomannan, glucose, glycerin, glyceryl glucoside, honey, hyaluronic acid, lactic acid, panthenol, polyethylene glycol, propylene glycol, propanediol, sodium hyaluronate, sodium lactate, sodium pyrrolidone carboxylic acid, sorbitol, and urea.

23. The formulation of claim 19 , wherein the formulation comprises 1-5% w/v of a cellulose polymer selected from the list consisting of: hydroxyethyl cellulose, methylcellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, ethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, and cellulose acetate.

24. The formulation of claim 19 , comprising a free amino acid selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

25. A method of treating a skin condition associated with Staphylococcus , the method comprising the step of applying the recombinant CWH of claim 1 to the skin.

26. The method of claim 25 , wherein the skin condition is selected from the list consisting of: an infection by a species of Staphylococcus , an overgrowth of a species of Staphylococcus , dry skin, itchy skin, red skin, atopic dermatitis, wound infection, acute radiation dermatitis, and a chronic wound.

27. The method of claim 25 , wherein the skin condition is atopic dermatitis.

28. The method of claim 25 , wherein the skin condition is associated with Staphylococcus aureus.

29. The method of claim 25 , wherein the recombinant CWH is applied to the skin 1-4 times per day until resolution of symptoms.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 13, 2024
From: SHOCK, TERESA; LIU, OLIVER; MILLER, MARITZA; SHOCK, JENNIFER
To: TOPAZ BIOSCIENCES, INC.
Reel/Frame 068579/0646 →
Continuity (4)
Continuation PCTUS2024034521 · Jun 18, 2024
Provisional Application 63639416 · Apr 26, 2024
Provisional Application 63509160 · Jun 20, 2023
Related Publication 20250000956A1 · Jan 2, 2025
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