IP Library Granted Patent US 10,688,163
Granted Patent B2
US 10,688,163 · App. 14/457,035 · Granted Jun 23, 2020

Targeted antimicrobials and related compositions, methods and systems

Inventors: Paul J. Jackson (Livermore, CA); Brian E. Souza (Livermore, CA); Feliza A. Bourguet (Livermore, CA); Matthew A. Coleman (Oakland, CA)
Assignee: Lawrence Livermore National Security, LLC
A61K38/50A61K45/06C12P1/04C12Q1/18C12Y305/01028G01N2333/32G01N2333/914
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Quick Facts
Patent No.
US 10,688,163
App. No.
14/457,035
Granted
Jun 23, 2020
Kind
B2
Abstract

Targeted antimicrobials are described and related, compositions, methods and systems.

Claims (85)

1. An antimicrobial composition comprising an effective amount of a targeted antimicrobial protein for Bacillus cereus or a microorganism related thereto,

a suitable vehicle, and

one or more polyamines and/or polymixins,

wherein the targeted antimicrobial protein has a catalytic domain and a binding domain, the targeted antimicrobial protein being BCZK2532 protein having SEQ ID NO: 3 and/or a related lysin protein having lytic activity,

wherein the related lysin protein has at least a 40% percentage identity with the BCZK2532 protein having SEQ ID NO: 3 or a portion thereof, and

wherein the related lysin protein has an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO: 3.

2. The antimicrobial composition of claim 1 , wherein the microorganism related thereto comprises B. anthracis, B. thuringiensis 97-27, B. thuringiensis HD1, B. thuringiensis HD560 and B. thuringiensis HD658.

3. The antimicrobial composition of claim 1 , wherein the related lysin protein has at least a 50% identity with the BCZK2532 protein or a portion thereof.

4. The antimicrobial composition of claim 1 , wherein the related lysin protein has at least an identity between 60% and 90% with the BCZK2532 protein or a portion thereof.

5. The antimicrobial composition of claim 1 , wherein the related lysin protein has at least a 90% identity with the BCZK2532 protein or a portion thereof.

6. The antimicrobial composition of claim 1 , wherein the related lysin protein has at least a 95% identity with the BCZK2532 protein or a portion thereof.

7. The antimicrobial composition of claim 1 , wherein the portion thereof is the catalytic domain and/or the binding domain of the BCZK2532 protein and wherein the catalytic domain and/or the binding domain of the related lysin protein has at least a 40% identity with the catalytic domain and/or the binding domain of the BCZK2532 protein.

8. The antimicrobial composition of claim 1 , wherein the portion thereof is the catalytic domain and/or the binding domain of the BCZK2532 protein and wherein the catalytic domain and/or the binding domain of the related lysin protein has at least a 50% identity with the catalytic domain and/or the binding domain of the BCZK2532 protein.

9. The antimicrobial composition of claim 1 , wherein the portion thereof is the catalytic domain and/or the binding domain of the BCZK2532 protein and wherein the catalytic domain and/or the binding domain of the related lysin protein has an identity of between 60% and 90% with the catalytic domain and/or the binding domain of the BCZK2532 protein.

10. The antimicrobial composition of claim 1 , wherein the portion thereof is the catalytic domain and/or the binding domain of the BCZK2532 protein and wherein the catalytic domain and/or the binding domain of the related lysin protein has at least a 90% identity with the catalytic domain and/or the binding domain of the BCZK2532 protein.

11. The antimicrobial composition of claim 1 , wherein the portion thereof is the catalytic domain and/or the binding domain of the BCZK2532 protein and wherein the catalytic domain and/or the binding domain of the related lysin protein has at least a 95% identity with the catalytic domain and/or the binding domain of the BCZK2532 protein.

12. The antimicrobial composition of claim 1 , wherein the composition comprises an additional one or more antimicrobials.

13. The antimicrobial composition of claim 12 , wherein the antimicrobial is one or more antibiotics.

14. The antimicrobial composition of claim 1 , wherein the vehicle is a pharmaceutically acceptable vehicle and the composition is a pharmaceutical composition.

15. The antimicrobial composition of claim 1 , wherein the targeted antimicrobial protein is in nanomolar concentrations.

16. The antimicrobial composition of claim 1 , wherein the antimicrobial composition is in a lyophilized form.

17. An antimicrobial composition comprising

an effective amount of a targeted antimicrobial protein for Bacillus cereus or a microorganism related thereto,

polyamines; and

a suitable vehicle,

wherein the targeted antimicrobial protein has a catalytic domain and a binding domain, the targeted antimicrobial protein being BCZK2532 protein having SEQ ID NO: 3 and/or a related lysin protein having lytic activity,

wherein the related lysin protein has at least a 40% percentage identity with the BCZK2532 protein having SEQ ID NO: 3 or a portion thereof, and

wherein the related lysin protein has an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO: 3.

18. The antimicrobial composition of claim 17 , wherein the antimicrobial composition is in a lyophilized form.

19. The antimicrobial composition of claim 17 , wherein the microorganism related thereto comprises B. anthracis, B. thuringiensis 97-27, B. thuringiensis HD1, B. thuringiensis HD560 and B. thuringiensis HD658.

20. The antimicrobial composition of claim 17 , wherein the portion thereof is the catalytic domain and/or the binding domain of the BCZK2532 protein and wherein the catalytic domain and/or the binding domain of the related lysin protein has at least a 90% identity with the catalytic domain and/or the binding domain of the BCZK2532 protein.

21. The antimicrobial composition of claim 17 , wherein the composition comprises an additional one or more antimicrobials.

22. The antimicrobial composition of claim 17 , wherein the composition comprises an additional one or more antibiotics.

23. The antimicrobial composition of claim 17 , wherein the vehicle is a pharmaceutically acceptable vehicle and the composition is a pharmaceutical composition.

24. An antimicrobial composition comprising

an effective amount of a targeted antimicrobial protein for Bacillus cereus or a microorganism related thereto,

a suitable vehicle,

one or more polyamines and/or polymixins,

wherein the targeted antimicrobial protein has a catalytic domain and a binding domain, the targeted antimicrobial protein being BCZK2532 protein having SEQ ID NO:3 and/or a related lysin protein having lytic activity,

wherein the related lysin protein has at least a 40% percentage identity with the BCZK2532 protein having SEQ ID NO:3 or a portion thereof, and

wherein the related lysin protein has an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO:3,

the targeted antimicrobial protein further comprising a tag.

25. The antimicrobial composition of claim 24 , wherein the antimicrobial composition is in a lyophilized form.

26. The antimicrobial composition of claim 24 , wherein the microorganism related thereto comprises B. anthracis, B. thuringiensis 97-27, B. thuringiensis HD1, B. thuringiensis HD560 and B. thuringiensis HD658.

27. The antimicrobial composition of claim 24 , wherein the portion thereof is the catalytic domain and/or the binding domain of the BCZK2532 protein and wherein the catalytic domain and/or the binding domain of the related lysin protein has at least a 90% identity with the catalytic domain and/or the binding domain of the BCZK2532 protein.

28. The antimicrobial composition of claim 24 , wherein the composition comprises one or more additional antimicrobials.

29. The antimicrobial composition of claim 28 , wherein the antimicrobial is one or more antibiotics.

30. The antimicrobial composition of claim 24 , wherein the vehicle is a pharmaceutically acceptable vehicle and the composition is a pharmaceutical composition.

31. An antimicrobial system comprising:

an effective amount of one or more targeted antimicrobial proteins specific for Bacillus cereus or one or more related microorganisms,

one or more polyamines and/or polymixins, and optionally

suitable reagents, and

an additional antimicrobial,

wherein the one or more targeted antimicrobial proteins comprise BCZK2532 protein having a SEQ ID NO: 3 and/or one or more related lysin proteins having lytic activity;

wherein the one or more related lysin proteins have at least a 40% percentage identity with the BCZK2532 protein having SEQ ID NO: 3 or a portion thereof, and

wherein the one or more related lysin proteins have an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO: 3.

32. An antimicrobial system comprising:

an effective amount of a targeted antimicrobial protein specific for Bacillus cereus or one or more related microorganisms;

polyamines;

suitable reagents, and

an additional antimicrobial,

wherein the targeted antimicrobial protein comprises BCZK2532 protein having a SEQ ID NO: 3 and/or one or more related lysin protein having lytic activity,

wherein the related lysin protein has at least a 40% percentage identity with the BCZK2532 protein having SEQ ID NO: 3 or a portion thereof, and

wherein the related lysin protein has an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO: 3.

33. An antimicrobial system comprising:

an effective amount of a targeted antimicrobial protein specific for Bacillus cereus or one or more related microorganisms, the one or more targeted antimicrobial protein comprising BCZK2532 protein having a SEQ ID NO: 3 and/or one or more a related lysin protein having lytic activity;

one or more polyamines and/or polymixins,

one or more antibiotics, and

optionally suitable reagents,

wherein the one or more related lysin protein has at least a 90% percentage identity with the BCZK2532 protein having SEQ ID NO: 3 or a portion thereof, and

wherein the one or more related lysin protein has an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO: 3,

the targeted antimicrobial protein further comprising a tag.

34. An antimicrobial method comprising

contacting a targeted antimicrobial BCZK2532 protein having SEQ ID NO: 3 and/or one or more related lysin proteins having lytic activity with a medium suitable to host Bacillus cereus or one or more related microorganisms, the contacting performed for a time and under condition to specifically kill or inhibit the growth of the one or more related microorganisms if present in the medium

wherein the one or more related lysin proteins have at least a 40% percentage identity with the BCZK2532 protein having SEQ ID NO:3 or a portion thereof, and

wherein the one or more related lysin proteins have an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO:3.

35. The antimicrobial method of claim 34 , wherein the medium is a solid and/or fluidic medium.

36. The antimicrobial method of claim 34 , wherein the one or more related microorganisms comprises B. anthracis, B. thuringiensis 97-27, B. thuringiensis HD1, B. thuringiensis HD560 and B. thuringiensis HD658.

37. The antimicrobial method of claim 34 , wherein the targeted antimicrobial BCZK2532 protein having SEQ ID NO:3 and/or one or more related lysin proteins having lytic activity is in combination with an additional antimicrobial.

38. An antimicrobial method, comprising:

administering to an individual in a therapeutically effective amount of a targeted antimicrobial BCZK2532 protein having a SEQ ID NO: 3 and/or one or more related lysin proteins having lytic activity to treat or prevent a condition associated with Bacillus cereus or one or more related microorganisms in the individual,

wherein the one or more related lysin proteins have at least a 40% percentage identity with the BCZK2532 protein having SEQ ID NO: 3 or a portion thereof, and

wherein the one or more related lysin proteins have an arginine in a position corresponding upon alignment to amino acid residue 100 of SEQ ID NO: 3.

39. The antimicrobial method of claim 38 , wherein the one or more related microorganisms comprises B. anthracis, B. thuringiensis 97-27, B. thuringiensis HD1, B. thuringiensis HD560 and B. thuringiensis HD658.

40. The antimicrobial method of claim 38 , wherein the targeted antimicrobial BCZK2532 protein having SEQ ID NO: 3 and/or one or more related lysin proteins having lytic activity is in combination with an additional antimicrobial.

Assignments (2)
CONFIRMATORY LICENSE Recorded Nov 5, 2014
From: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
To: U.S. DEPARTMENT OF ENERGY
Reel/Frame 034104/0477 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 4, 2014
From: JACKSON, PAUL J.; SOUZA, BRIAN E.; BOURGUET, FELIZA A.; COLEMAN, MATTHEW A.
To: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
Reel/Frame 033665/0180 →
Continuity (3)
Continuation 12852358 · Aug 6, 2010
Provisional Application 61232345 · Aug 7, 2009
Related Publication 20140369990A1 · Dec 18, 2014