Patent Application

App. No. 17/179,295

Abstract

Claims (70)

1 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 1.

2 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1.

3 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 2.

4 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

5 . The bacteriophage of claim 1 , wherein the bacteriophage is resistant to blood complement inactivation.

6 . A bacteriophage composition comprising one or more bacteriophage selected from a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

7 . The bacteriophage composition of claim 6 , comprising two or more of the bacteriophage selected from the bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2; and wherein the composition's target bacteria range is more effective than the sum of the efficacy of individual bacteriophages in the composition.

8 . The bacteriophage composition of claim 6 , wherein the bacteriophage infect and kill Staphylococcus aureus.

9 . The bacteriophage composition of claim 6 , further comprising a storage media for storage at a temperature at or below 8° C.

10 . The bacteriophage composition of claim 6 , wherein the bacteriophage is resistant to blood complement inactivation.

11 . The bacteriophage composition of claim 6 , wherein the one or more bacteriophage belong to the genus Silviavirus.

12 . The composition of claim 6 , wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1.

13 . The composition of claim 6 , wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 1.

14 . The composition of claim 6 , wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

15 . The composition of claim 6 , wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 2.

16 . The composition of claim 6 , wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1 and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

17 . The composition of claim 6 , wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 1 and a bacteriophage having a genome comprising the polynucleotide sequence of SEQ ID NO: 2.

18 . The bacteriophage composition of claim 6 , wherein the composition is substantially free of a bacterial component.

19 . The composition of claim 18 , wherein the bacterial component comprises bacterial host protein.

20 . The composition of claim 6 , wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, excipient or combinations thereof.

21 . The composition of claim 6 , wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.

22 . The composition of claim 6 , wherein the bacteriophages of the composition target one or more of vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-resistant Staphylococcus aureus (VRSA), methicillin-resistant (MRSA) Staphylococcus aureus.

23 . The composition of claim 22 , wherein the bacteriophages infect and kill one or more of vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-resistant Staphylococcus aureus (VRSA), methicillin-resistant Staphylococcus aureus (MRSA).

24 . The composition of claim 6 , wherein the composition comprises between 1×10 8 and 1×10 11 PFU of each bacteriophage.

25 . The composition of claim 6 , wherein the composition is to be administered at a dosage of at least 1×10 9 PFU of total bacteriophages per milliliter.

26 . The composition of claim 6 , wherein the composition is stored at 2-8° C.

27 . The composition of claim 6 , wherein at least one bacteriophage is obligately lytic.

28 . The bacteriophage or composition of claim 6 , wherein the sequence of at least one bacteriophage is genetically modified.

29 . A method of treating a bacterial infection comprising administering the bacteriophage or composition of claim 6 to a subject in need of treatment.

30 . Use of a composition according to claim 6 in the treatment of a S. aureus infection in a subject, the use comprising administering the composition to a subject suffering from a S. aureus infection.

31 . Use of a composition comprising one or more distinct bacteriophages that target Staphylococcus aureus in the treatment of a subject with a Staphylococcus aureus bacterial infection comprising administering the composition to said subject; wherein at least one of said one or more bacteriophages is selected from a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

32 . The use of claim 31 , wherein the bacteriophage is resistant to blood complement inactivation.

33 . A bacterial host manufacturing strain comprising a bacteriophage wherein said bacteriophage comprises a polynucleotide sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

34 . A method of treating a subject with a bacterial infection comprising selecting a bacteriophage based upon resistance to blood complement inactivation and administering said bacteriophage to the subject.

35 . The method of claim 34 , comprising selecting a bacteriophage based upon resistance to complement C3 protein-mediated inactivation.

36 . The method of claim 34 , wherein the bacteriophage comprises a polynucleotide sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

37 . A method of treating a subject with a bacterial infection comprising administering to the subject one or more distinct bacteriophages selected from a bacteriophage comprising a polynucleotide sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

38 . The method of claim 37 , wherein the bacterial infection is at least partially due to Staphylococcus aureus.

39 . The method of claim 38 , wherein the one or more distinct bacteriophages infect and kill Staphylococcus aureus.

40 . A method of modifying the microbial flora in a subject comprising administering to said subject at least one bacteriophage that targets Staphylococcus aureus bacteria, wherein said bacteriophage comprises a polynucleotide sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

41 . The method of claim 37 , wherein the bacteriophage is resistant to blood complement inactivation.

42 . The method of claim 37 , wherein the one or more phage are selected based upon resistance to complement C3 protein-mediated inactivation.

43 . The method of claim 37 , wherein the distinct bacteriophage belongs to the genus Silviavirus.

44 . The method of claim 34 , wherein the bacteriophage comprises a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1.

45 . The method of claim 34 , wherein the bacteriophage comprises a polynucleotide sequence of SEQ ID NO: 1.

46 . The method of claim 34 , wherein the bacteriophage comprises a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

47 . The method of claim 34 , wherein the bacteriophage comprises a polynucleotide sequence of SEQ ID NO: 2.

48 . The method of claim 34 , wherein the bacteriophage comprises a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1 and a bacteriophage comprises a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

49 . The method of claim 34 , wherein the method comprises administering a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 1 and a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 2.

50 . The method of claim 34 , wherein at least about 80% of bacteriophages retain lytic activity after exposure to human plasma for a time period between about 10 minutes and about 120 minutes.

51 . The method of claim 50 , wherein the time period is between about 10 minutes and about 90 minutes.

52 . The method of claim 34 , wherein the bacterial infection comprises a pulmonary infection, rhinosinusitis, urinary tract infection, intra-abdominal infection, skin infection, skin structure infection, bacteremia, septicemia, endocarditis, or an implant infection.

53 . The method of claim 52 , wherein the implant infection comprises a cardiac implant infection (e.g., ventricular assist device infection, pacemaker infection), prosthetic joint infection, or prosthetic valve endocarditis.

54 . The method of claim 34 , wherein the bacterial infection is bacteremia.

55 . The method of claim 34 , wherein the bacterial infection is resistant to an antibiotic.

56 . The method of claim 34 , wherein the bacteriophages are administered at 1×10 8 to 1×10 11 plaque forming units (PFU) of total bacteriophages.

57 . The method of claim 34 , wherein the bacteriophages are administered at between 1×10 1 and 1×10 11 PFU of each bacteriophage.

58 . The method of claim 34 , wherein the bacteriophage is administered in a dosage of one milliliter comprising 2×10 9 PFU total bacteriophage.

59 . The method of claim 34 , wherein the method further comprises administration of an antibiotic.

60 . The method of claim 59 , wherein the antibiotic is from an antibiotic class selected from the group consisting of a fluoroquinolone, carbapenem, aminoglycoside, ansamycin, cephalosporin, penicillin, beta lactam, beta lactamase inhibitor, folate pathway inhibitor, fucidane, glycopeptide, glycylcycline, lincosamide, lipopeptide, macrolide, oxazolidinone, phenicol phosphonic acid, streptogramin, and tetracycline.

61 . The method of claim 34 , wherein the bacteriophage is administered intravenously.

62 . The method of claim 34 , wherein the bacteriophage is administered via intra-articular injection.

63 . The method of claim 34 , wherein the bacteriophage is administered via inhalation.

64 . The method of claim 34 , wherein the bacteriophage is administered via nebulization.

65 . The method of claim 34 , wherein the bacteriophage is administered at least every 6 hours.

66 . The method of claim 34 , wherein the bacteriophage is administered at least every 12 hours.

67 . The method of claim 34 , wherein the bacteriophage is administered at least every 24 hours.

68 . The method of claim 34 , wherein the bacteriophage is administered for at least 7 days.

69 . The method of claim 34 , wherein the subject is human.

70 . The bacteriophage of claim 3 , wherein the bacteriophage is resistant to blood complement inactivation.

Assignments (8)