Patent Application

App. No. 17/917,543

Abstract

Claims (205)

1 . A bacteriophage composition comprising one or more bacteriophages comprising a polynucleotide sequence selected from the polynucleotide sequence of SEQ ID NO: 1, a polynucleotide sequence of SEQ ID NO: 2, a polynucleotide sequence of SEQ ID NO: 3, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2, and/or a polynucleotide sequence with at least 90% identity to SEQ ID NO: 3.

2 . The bacteriophage composition of claim 1 , comprising two or more bacteriophages, wherein a first bacteriophage of the two or more bacteriophages comprises a polynucleotide sequence selected from the polynucleotide sequence of SEQ ID NO: 1, a polynucleotide sequence of SEQ ID NO: 2, or a polynucleotide sequence of SEQ ID NO: 3, and wherein a second bacteriophage of the two or more bacteriophages comprises a naturally occurring phage.

3 . The bacteriophage composition of claim 1 , comprising two or more bacteriophages comprising a polynucleotide sequence selected from the polynucleotide sequence of SEQ ID NO: 1, the polynucleotide sequence of SEQ ID NO: 2, the polynucleotide sequence of SEQ ID NO: 3, the polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, the polynucleotide sequence with at least 90% identity to SEQ ID NO: 2, and/or the polynucleotide sequence with at least 90% identity to SEQ ID NO: 3.

4 . The bacteriophage composition of claim 3 , wherein the composition's target bacteria range is broader than the cumulative range of the individual bacteriophages in the composition.

5 . The bacteriophage composition of claim 4 , wherein the target bacteria range is broadened within a bacterial species that the bacteriophage is able to infect.

6 . The bacteriophage composition of claim 1 , further comprising at least one bacteriophage comprising a polynucleotide sequence selected from the polynucleotide sequence of SEQ ID NO: 4, the polynucleotide sequence of SEQ ID NO: 5, the polynucleotide sequence of SEQ ID NO: 6, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 4, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 5, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 6.

7 . A bacteriophage composition comprising one or more bacteriophages comprising a polynucleotide sequence selected from the polynucleotide sequence of SEQ ID NO: 4, a polynucleotide sequence of SEQ ID NO: 5, a polynucleotide sequence of SEQ ID NO: 6, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 4, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 5, and/or a polynucleotide sequence with at least 90% identity to SEQ ID NO:6.

8 . The bacteriophage composition of claim 7 , comprising two or more bacteriophages, wherein a first bacteriophage of the two or more bacteriophages comprises a polynucleotide sequence selected from the polynucleotide sequence of SEQ ID NO: 4, a polynucleotide sequence of SEQ ID NO: 5, or a polynucleotide sequence of SEQ ID NO: 6, and wherein a second bacteriophage of the two or more bacteriophages comprises a naturally occurring phage.

9 . The bacteriophage composition of claim 8 , comprising two or more bacteriophages comprising a polynucleotide sequence selected from the polynucleotide sequence of SEQ ID NO: 4, the polynucleotide sequence of SEQ ID NO: 5, the polynucleotide sequence of SEQ ID NO: 6, the polynucleotide sequence with at least 90% identity to SEQ ID NO: 4, the polynucleotide sequence with at least 90% identity to SEQ ID NO: 5, and/or the polynucleotide sequence with at least 90% identity to SEQ ID NO: 6.

10 . The bacteriophage composition of claim 9 , wherein the composition's target bacteria range is broader than the cumulative range of the individual bacteriophage in the composition.

11 . The bacteriophage composition of claim 10 , wherein the target bacteria range is broadened within a bacterial species that the bacteriophage is able to infect.

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

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

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

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

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

17 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 3.

18 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 4.

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

20 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 5.

21 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 5.

22 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 6.

23 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 6.

24 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 7.

25 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 7.

26 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 8.

27 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 8.

28 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 9.

29 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 9.

30 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 10.

31 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 10.

32 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 11.

33 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 11.

34 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 12.

35 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 12.

36 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 13.

37 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 13.

38 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 14.

39 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 14.

40 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 15.

41 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 15.

42 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 16.

43 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 16.

44 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 17.

45 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 17.

46 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 18.

47 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 18.

48 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 19.

49 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 19.

50 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 20.

51 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 20.

52 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 21.

53 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 21.

54 . An isolated, purified bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 22.

55 . An isolated, purified bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 22.

56 . The bacteriophage of any one of claims 12 - 55 , wherein the bacteriophage is resistant to sputum inactivation.

57 . The bacteriophage of any one of claims 12 - 56 , wherein the bacteriophage persists in the lung and/or bronchoalveolar lavage fluid up to 48 hours after administration.

58 . The bacteriophage of any one of claims 12 - 57 , wherein the bacteriophage maintains activity in the presence of a pulmonary treatment selected from salbutamol, tobramycin, aztreonam, colistin, inhaled hypertonic saline, and inhaled beta-agonist.

59 . A bacteriophage composition comprising two or more bacteriophages, wherein at least one of the bacteriophages comprises a polynucleotide sequence having at least 90% identity to a sequence selected from the polynucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22; and wherein at least one other bacteriophage infects a pseudomonas bacteria.

60 . The bacteriophage composition of claim 59 , wherein the composition comprises at least two bacteriophages where each bacteriophage comprises a separate polynucleotide sequence having at least 90% identity to a sequence selected from the polynucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

61 . The bacteriophage composition of claim 59 , wherein the composition comprises at least three bacteriophages where each bacteriophage comprises a separate polynucleotide sequence having at least 90% identity to a sequence selected from the polynucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

62 . The bacteriophage composition of any of claims 59 - 61 , wherein the composition comprises at least one bacteriophage comprising a sequence having at least 90% identity to a sequence selected from the polynucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, and 6.

63 . The bacteriophage composition of claim 62 , wherein the composition comprises at least two bacteriophages, each bacteriophage comprising a different polynucleotide sequence having at least 90% identity to a sequence selected from the polynucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, and 6.

64 . The bacteriophage composition of claim 63 , wherein the composition further comprises at least one bacteriophage comprising a polynucleotide sequence having at least 90% identity to a sequence selected from 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

65 . A bacteriophage composition comprising one or more bacteriophages comprising a polynucleotide sequence having 90% to 100% identity to a sequence selected from the polynucleotide sequence of SEQ ID NO: 1, a polynucleotide sequence of SEQ ID NO: 2, a polynucleotide sequence of SEQ ID NO: 3, a polynucleotide sequence of SEQ ID NO: 4, a polynucleotide sequence of SEQ ID NO: 5, a polynucleotide sequence of SEQ ID NO: 6.

66 . The bacteriophage composition of claim 65 , comprising two or more bacteriophages selected from the polynucleotide sequence of SEQ ID NO: 1, a polynucleotide sequence of SEQ ID NO: 2, a polynucleotide sequence of SEQ ID NO: 3, a polynucleotide sequence of SEQ ID NO: 4, a polynucleotide sequence of SEQ ID NO: 5, or a polynucleotide sequence of SEQ ID NO: 6.

67 . The bacteriophage composition of claim 65 , comprising three or more bacteriophages selected from the polynucleotide sequence of SEQ ID NO: 1, a polynucleotide sequence of SEQ ID NO: 2, a polynucleotide sequence of SEQ ID NO: 3, a polynucleotide sequence of SEQ ID NO: 4, a polynucleotide sequence of SEQ ID NO: 5, or a polynucleotide sequence of SEQ ID NO: 6.

68 . The bacteriophage composition of claim 65 , comprising four or more bacteriophages selected from the polynucleotide sequence of SEQ ID NO: 1, a polynucleotide sequence of SEQ ID NO: 2, a polynucleotide sequence of SEQ ID NO: 3, a polynucleotide sequence of SEQ ID NO: 4, a polynucleotide sequence of SEQ ID NO: 5, or a polynucleotide sequence of SEQ ID NO: 6.

69 . The bacteriophage composition of claim 65 , comprising five or more bacteriophages selected from the polynucleotide sequence of SEQ ID NO: 1, a polynucleotide sequence of SEQ ID NO: 2, a polynucleotide sequence of SEQ ID NO: 3, a polynucleotide sequence of SEQ ID NO: 4, a polynucleotide sequence of SEQ ID NO: 5, or a polynucleotide sequence of SEQ ID NO: 6.

70 . The bacteriophage composition of claim 69 , further comprising a bacteriophage comprising a nucleic acid sequence having 90%-100% identity to a sequence selected from a polynucleotide sequence of SEQ ID NO: 7, a polynucleotide sequence of SEQ ID NO: 8, a polynucleotide sequence of SEQ ID NO: 9, a polynucleotide sequence of SEQ ID NO: 10, a polynucleotide sequence of SEQ ID NO: 11, a polynucleotide sequence of SEQ ID NO: 12, a polynucleotide sequence of SEQ ID NO: 13, a polynucleotide sequence of SEQ ID NO: 14, a polynucleotide sequence of SEQ ID NO: 15, a polynucleotide sequence of SEQ ID NO: 16, a polynucleotide sequence of SEQ ID NO: 17, a polynucleotide sequence of SEQ ID NO: 18, a polynucleotide sequence of SEQ ID NO: 19, a polynucleotide sequence of SEQ ID NO: 20, a polynucleotide sequence of SEQ ID NO: 21, a polynucleotide sequence of SEQ ID NO: 22.

71 . The bacteriophage composition of claim 70 wherein the bacteriophage comprises a polynucleotide sequence with at least a 90% identity to SEQ ID NO: 7, a polynucleotide with at least a 93% identity to SEQ ID NO: 8, a polynucleotide sequence with at least 93% identity to SEQ ID NO: 9, a polynucleotide sequence with at least 89% identity to SEQ ID NO: 10, a polynucleotide sequence with at least 95% identity to SEQ ID NO: 11, a polynucleotide sequence with at least 91% identity to SEQ ID NO: 12, a polynucleotide sequence with at least 92% identity to SEQ ID NO: 13, a polynucleotide sequence with at least 96% identity to SEQ ID NO: 14 a polynucleotide sequence with at least 95% identity to SEQ ID NO: 15, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 16, a polynucleotide sequence with at least 92% identity to SEQ ID NO: 17, a polynucleotide sequence with at least 95% identity to SEQ ID NO: 18, a polynucleotide sequence with at least 96% identity to SEQ ID NO: 19, a polynucleotide sequence with at least 96% identity to SEQ ID NO: 20, a polynucleotide sequence with at least 96% identity to SEQ ID NO: 21, a polynucleotide sequence with at least 95% identity to SEQ ID NO: 22.

72 . The bacteriophage composition of any one of the preceding claims, wherein at least one of the bacteriophages infect and kill Pseudomonas aeruginosa.

73 . The bacteriophage composition of any of the preceding claims, further comprising a storage medium for storage at room temperature or a temperature at or below 8° C.

74 . The bacteriophage composition of claim 73 , wherein the storage medium comprises a cryoprotectant.

75 . The bacteriophage composition of any one of the preceding claims, wherein the bacteriophage is resistant to sputum inactivation.

76 . The bacteriophage composition of any of the preceding claims, wherein the bacteriophage remains in the lung and/or bronchoalveolar lavage fluid up to 72 hours after administration.

77 . The bacteriophage composition of any of the preceding claims, wherein the bacteriophage maintains activity in the presence of a pulmonary treatment selected from salbutamol, tobramycin, aztreonam, colistin, inhaled hypertonic saline, and inhaled beta-agonist.

78 . The bacteriophage composition of any of the preceding claims, wherein one or more bacteriophages belong to the Family Podoviridae or Myoviridae.

79 . The bacteriophage composition of claim 78 , wherein one or more phage belong to the Family Myoviridae.

80 . The bacteriophage composition of claim 79 , wherein one or more phage belong to the Genus Pbunavirus.

81 . The bacteriophage composition of claim 79 , wherein one or more phage belong to the Genus Pakpunavirus.

82 . The bacteriophage composition of claim 79 , wherein one or more phage belong to the Genus Nankokuvirus.

83 . The bacteriophage composition of claim 78 , wherein one or more phage belong to the Family Podoviridae.

84 . The bacteriophage composition of claim 83 , wherein one or more phage belong to the Genus Phikmvvirus.

85 . The bacteriophage composition of claim 83 , wherein one or more phage belong to the Genus Litunavirus.

86 . The bacteriophage composition of claim 83 , wherein one or more phage belong to the Genus Bruynoghevirus.

87 . The bacteriophage composition of claim 83 , wherein one or more phage belong to the Genus Luzseptimavirus.

88 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1.

89 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 1.

90 . The composition of any one of the preceding claims, wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2.

91 . The composition of any one of the preceding claims, wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 2.

92 . The composition of any one of the preceding claims, wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 3.

93 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 3.

94 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 4.

95 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 4.

96 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 5.

97 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 5.

98 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 6.

99 . The composition of any of the preceding claims, wherein the composition comprises a bacteriophage comprising the polynucleotide sequence of SEQ ID NO: 6.

100 . The bacteriophage composition of any of the preceding claims, wherein the composition is substantially free of a bacterial component.

101 . The composition of claim 100 , wherein the bacterial component comprises bacterial host protein and/or exotoxin.

102 . The composition of any one of the preceding claims, wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, excipient or combinations thereof.

103 . The composition of any of the preceding claims, wherein the composition is formulated for nebulization.

104 . The composition of any of the preceding claims, wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.

105 . The composition of any of the preceding claims, wherein the bacteriophage of the composition targets one or more of Pseudomonas aeruginosa , antibiotic-resistant Pseudomonas aeruginosa , and multiple antibiotic-resistant Pseudomonas aeruginosa.

106 . The composition of claim 105 , wherein the bacteriophages infect and kill one or more of Pseudomonas aeruginosa , antibiotic-resistant Pseudomonas aeruginosa , and multiple antibiotic-resistant Pseudomonas aeruginosa.

107 . The composition of any of the preceding claims, wherein the composition comprises between 1×10 8 and 1×10 11 PFU per milliliter of each bacteriophage.

108 . The composition of any one of the preceding claims, wherein the composition is to be administered at a dosage of at least 3×10 8 PFU of total bacteriophages per milliliter per dose.

109 . The composition of any of the preceding claims, wherein the composition is stored at a temperature ranging from −20° C. to 25° C.

110 . The composition of any of the preceding claims, wherein the composition is stored at 2° C. to 8° C.

111 . The composition of any of the preceding claims, wherein at least one bacteriophage is obligately lytic.

112 . The bacteriophage or composition of any one of the preceding claims, wherein the sequence of at least one bacteriophage is genetically modified.

113 . A bacteriophage composition comprising, consisting essentially of, or consisting of a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 1, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 2, and a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 3.

114 . A bacteriophage composition comprising, consisting essentially of, or consisting of a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 4, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 5, and a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 6.

115 . The bacteriophage composition of claim 114 , further comprising one or more bacteriophages selected from a bacteriophage comprising a polynucleotide sequence with 90%-100% identity to a sequence of SEQ ID NO: 4, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 5, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 6, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 7, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 8, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 9, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 10, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 11, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 12, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 13, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 14, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 15, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 16, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 17, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 18, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 19, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 20, a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 21, or a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 22.

116 . A bacteriophage composition comprising: a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2, and a bacteriophage comprising polynucleotide sequence with at least 90% identity to SEQ ID NO: 3.

117 . A bacteriophage composition comprising: a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 4, a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 5, and a bacteriophage comprising polynucleotide sequence with at least 90% identity to SEQ ID NO:6.

118 . The bacteriophage composition of claim 116 or claim 117 , further comprising one or more bacteriophages selected from a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

119 . The bacteriophage composition of claim 118 , wherein the one or more bacteriophages comprises a polynucleotide sequence with at least 90% identity to SEQ ID NO: 7, a bacteriophage comprising a polynucleotide sequence with at least 93% identity to SEQ ID NO: 8, a bacteriophage comprising a polynucleotide sequence with at least 93% identity to SEQ ID NO: 9, a bacteriophage comprising a polynucleotide sequence with at least 89% identity to SEQ ID NO: 10, a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO: 11, a bacteriophage comprising a polynucleotide sequence with at least 91% identity to SEQ ID NO: 12, a bacteriophage comprising a polynucleotide sequence with at least 92% identity to SEQ ID NO: 13, a bacteriophage comprising a polynucleotide sequence with at least 96% identity to SEQ ID NO: 14, a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO: 15, a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO: 16, a bacteriophage comprising a polynucleotide sequence with at least 92% identity to SEQ ID NO: 17, a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO: 18, a bacteriophage comprising a polynucleotide sequence with at least 96% identity to SEQ ID NO: 19, a bacteriophage comprising a polynucleotide sequence with at least 96% identity to SEQ ID NO: 20, a bacteriophage comprising a polynucleotide sequence with at least 96% identity to SEQ ID NO: 21, or a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO: 22.

120 . The bacteriophage composition of claim 118 , wherein the composition's target bacteria range is broader than the cumulative range of the individual bacteriophages in the composition.

121 . The bacteriophage composition of claim 118 , wherein the target bacteria range is broadened within a bacterial species that the bacteriophage is able to infect.

122 . The bacteriophage composition of any one of claims 116 - 121 , wherein the bacteriophages infect and kill Pseudomonas aeruginosa.

123 . The bacteriophage composition of any one of claims 116 - 122 , wherein the composition is stored at a temperature ranging from −20-25° C.

124 . The bacteriophage composition of any of claims 116 - 123 , further comprising a storage medium for storage at a temperature at or below 8° C., such as at 4° C., 0° C., −20° C., or −80° C.

125 . The bacteriophage composition of any one of claims 116 - 124 , wherein the bacteriophage is resistant to sputum inactivation.

126 . The bacteriophage composition of any one of claims 116 - 125 , wherein the bacteriophage persists in the lung and/or bronchoalveolar lavage fluid up to 48 hours after administration.

127 . The bacteriophage composition of any one of claims 116 - 126 , wherein the bacteriophages reduce biofilm mass.

128 . The bacteriophage composition of any one of claims 116 - 127 , wherein the bacteriophage maintains activity in the presence of a pulmonary treatment selected from salbutamol, tobramycin, aztreonam, colistin, inhaled hypertonic saline, and inhaled beta-agonist.

129 . The bacteriophage composition of any one of claims 116 - 128 , wherein one or more bacteriophages belong to the Family Podoviridae and/or Myoviridae.

130 . The bacteriophage composition of any of claims 116 - 129 , wherein the composition is substantially free of a bacterial component.

131 . The composition of claim 130 , wherein the bacterial component comprises bacterial host protein.

132 . The composition of any one of claims 116 - 131 , wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, excipient or combinations thereof.

133 . The composition of any one of claims 116 - 132 , wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.

134 . The composition of any one of claims 116 - 133 , wherein the bacteriophage of the composition targets one or more of Pseudomonas aeruginosa , antibiotic-resistant Pseudomonas aeruginosa , and/or multiple antibiotic-resistant Pseudomonas aeruginosa.

135 . The composition of claim 134 , wherein the bacteriophages infect and kill one or more of Pseudomonas aeruginosa , antibiotic-resistant Pseudomonas aeruginosa , and/or multiple antibiotic-resistant Pseudomonas aeruginosa.

136 . The composition of any one of claims 116 - 135 , wherein the composition comprises between 1×10 8 and 1×10 11 PFU per milliliter of each bacteriophage.

137 . The composition of any one of claims 116 - 136 , wherein the composition is to be administered at a dosage of at least 3×10 8 PFU of total bacteriophages per milliliter.

138 . The composition of any one of claims 116 - 137 , wherein the composition is stored at a temperature ranging from −20° C. to 25° C.

139 . The composition of claim 138 , wherein the composition is stored at 2° C. to 8° C.

140 . The composition of any one of claims 116 - 139 , wherein at least one bacteriophage is obligately lytic.

141 . The composition of any one of claims 116 - 140 , wherein the sequence of at least one bacteriophage is genetically modified.

142 . A method of treating a bacterial infection comprising administering the bacteriophage or composition of any one of the preceding claims.

143 . Use of a composition according to any one of claims 1 - 141 in the treatment of a Pseudomonas aeruginosa infection in a subject, the use comprising administering the composition to a subject suffering from a Pseudomonas aeruginosa infection.

144 . Use of a composition comprising one or more distinct bacteriophages that target Pseudomonas aeruginosa in the treatment of subject with a Pseudomonas aeruginosa 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, SEQ ID NO: 3, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 1, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 2, and a polynucleotide sequence with at least 85% identity to SEQ ID NO: 3.

145 . Use of a composition comprising one or more distinct bacteriophages that target Pseudomonas aeruginosa in the treatment of subject with a Pseudomonas aeruginosa 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: 4, SEQ ID NO: 5, SEQ ID NO: 6, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 4, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 5, and a polynucleotide sequence with at least 85% identity to SEQ ID NO: 6.

146 . Use of a composition comprising one or more distinct bacteriophages that target Pseudomonas aeruginosa in the treatment of subject with a Pseudomonas aeruginosa 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, SEQ ID NO: 3, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 1, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 2, and a polynucleotide sequence with at least 85% identity to SEQ ID NO: 3; and at least one additional bacteriophage selected from a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 4, a polynucleotide sequence with at least 85% identity to SEQ ID NO: 5, and a polynucleotide sequence with at least 85% identity to SEQ ID NO: 6.

147 . The use of any of claims 144 - 146 , further comprising the use of one or more bacteriophages comprising a nucleic acid sequence having 85%-100% sequence identity to a sequence selected from SEQ ID No. 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

148 . The use of claims 143 - 147 , wherein the bacteriophage is resistant to sputum inactivation.

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

150 . The method of claim 149 , wherein the bacteriophage is selected from a bacteriophage comprising a polynucleotide sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 1, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 2, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 3, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 4, a polynucleotide sequence with at least 90% identity to SEQ ID NO: 5, and a polynucleotide sequence with at least 90% identity to SEQ ID NO: 6.

151 . The method of claim 149 or 150 , wherein the bacteriophage is selected from a bacteriophage comprising a polynucleotide sequence with 80%-100% identity to a sequence selected from SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

152 . 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 having 85%-100% identity to a sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

153 . The method of claim 152 , wherein the one or more bacteriophages comprise a bacteriophage selected from a bacteriophage comprising a polynucleotide sequence having 85%-100% identity to a sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, and 6.

154 . The method of claim 152 , wherein the method comprises at least two bacteriophages, and at least one of the at least two bacteriophages is a bacteriophage selected from a bacteriophage comprising a polynucleotide sequence having 85%-100% identity to a sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, and 6.

155 . The method of claim 153 or 154 , wherein the bacteriophage comprises a polynucleotide sequence having at least 85% identity to a sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, and 6.

156 . The method of claim 155 , wherein the bacteriophage comprises a polynucleotide sequence having at least 90% identity to a sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, and 6.

157 . The method of claim 155 , wherein the bacteriophage comprises a polynucleotide sequence having at least 95% identity to a sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, and 6.

158 . The method of claim 155 , wherein the bacteriophage comprises a polynucleotide sequence having at least 99% identity to a sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, and 6.

159 . The method of claim 155 , wherein the bacteriophage comprises a polynucleotide sequence sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, and 6.

160 . The method of any of claims 153 - 159 , further comprising one or more bacteriophages comprising a polynucleotide sequence having 85%-100% identity to a sequence selected from SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22.

161 . The method any of claims 152 - 160 , wherein the one or more bacteriophages comprise a bacteriophage selected from a bacteriophage comprising a polynucleotide sequence having 85%-100% identity to a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3.

162 . The method of any of claims 152 - 160 , wherein the one or more distinct bacteriophages are selected from a bacteriophage comprising a polynucleotide sequence having 85%-100% identity to a sequence selected from SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.

163 . The method of any one of claims 149 - 162 , wherein the bacterial infection is at least partially due to Pseudomonas aeruginosa.

164 . The method of any one of claims 149 - 163 , wherein the one or more distinct bacteriophages infect and kill Pseudomonas aeruginosa.

165 . The method of any one of claims 149 - 164 , wherein the bacteriophages are the primary treatment.

166 . The method of any one of claims 149 - 165 , wherein the bacteriophages are applied to an infection that was previously unresolved by treatment with antibiotics.

167 . The method of any one of claims 149 - 166 , 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 100 minutes.

168 . The method of claim 167 , wherein the time period is between about 10 minutes and about 90 minutes.

169 . The method of any one of claims 149 - 168 , wherein the bacterial infection comprises a pulmonary infection, and/or rhinosinusitis.

170 . The method of any one of claims 149 - 168 , wherein the subject has a bacterial infection and a lung fibrosis condition.

171 . The method of any one of claims 149 - 170 , wherein the infection comprises a bacterial infection in the presence of cystic fibrosis, non-cystic fibrosis bronchiectasis (NCFB), and/or pneumonia.

172 . The method of any one of claims 149 - 171 , wherein the bacterial infection is resistant to an antibiotic.

173 . The method of any one of claims 149 - 172 , wherein the bacteriophages are administered in combination with an antibiotic class selected from a fluoroquinolone, carbapenem, aminoglycoside, ansamycin, cephalosporin, penicillin, beta lactam, beta lactamase inhibitor, folate pathway inhibitor, fucidane, glycopeptide, glycylcycline, lincosamide, lipopeptide, macrolide, quinolone, oxazolidinone, phenicol phosphonic acid, streptogramin, tetracycline, sulfonamide, imipenem, meropenem, amikacin, ciprofloxacin, levofloxacin, tobramycin, azithromycin, aztreonam, colistin, inhaled tobramycin, inhaled aztreonam, and inhaled colistin.

174 . The method of any one of claims 149 - 173 , wherein the bacterial infection has become resistant to antibiotics selected from a fluoroquinolone, carbapenem, aminoglycoside, ansamycin, cephalosporin, penicillin, beta lactam, beta lactamase inhibitor, folate pathway inhibitor, fucidane, glycopeptide, glycylcycline, lincosamide, lipopeptide, macrolide, quinolone, oxazolidinone, phenicol phosphonic acid, streptogramin, tetracycline, sulfonamide, imipenem, meropenem, amikacin, ciprofloxacin, levofloxacin, tobramycin, azithromycin, aztreonam, colistin, inhaled tobramycin, inhaled aztreonam, and inhaled colistin.

175 . The method of any one of claims 149 - 174 , wherein the bacteriophages are administered at between 1×10 8 and 1×10 11 PFU of each bacteriophage.

176 . The method of claim 175 , wherein the bacteriophages are administered at least 3×10 8 plaque forming units (PFU) of total bacteriophages.

177 . The method of any one of claims 149 - 176 , wherein the bacteriophage is administered in a dosage comprising at least about 1×10 8 PFU of each bacteriophage.

178 . The method of any one of claims 149 - 177 , wherein the method further comprises administration of an antibiotic.

179 . The method of claim 178 , wherein the antibiotic is a fluoroquinolone, carbapenem, aminoglycoside, ansamycin, cephalosporin, penicillin, beta lactam, beta lactamase inhibitor, folate pathway inhibitor, fucidane, glycopeptide, glycylcycline, lincosamide, lipopeptide, macrolide, quinolone, oxazolidinone, phenicol phosphonic acid, streptogramin, tetracycline, sulfonamide, imipenem, meropenem, amikacin, ciprofloxacin, levofloxacin, tobramycin, azithromycin, aztreonam, colistin, inhaled tobramycin, inhaled aztreonam, or inhaled colistin.

180 . The method of any one of claims 149 - 179 , wherein the method further comprises administration of a treatment for cystic fibrosis.

181 . The method of claim 180 , wherein the treatment for cystic fibrosis is selected from CFTR modulator therapies, mucus thinners, airway clearance techniques, inhaled corticosteroids, oral corticosteroids, leukotriene modifiers, inhaled anticholinergics, dornase alfa, inhaled bronchodilators, inhaled hypertonic saline, and inhaled beta-agonists.

182 . The method of any one of claims 149 - 181 , wherein the bacteriophage is administered via inhalation.

183 . The method of any one of claims 149 - 182 , wherein the bacteriophage is administered via nebulization.

184 . The method of any one of claims 149 - 183 , wherein the bacteriophage is administered at least every 6 hours.

185 . The method of any one of claims 149 - 184 , wherein the bacteriophage is administered for at least one day.

186 . The method of any one of claims 149 - 185 , wherein the subject is human.

187 . A method of treating non-cystic fibrosis bronchiectasis (NCFB) comprising administering one or more bacteriophages that target bacteria in the genus Pseudomonas.

188 . The method of claim 187 , wherein the bacteriophages comprise one or more bacteriophages selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, and/or SEQ ID NO: 22.

189 . A bacterial host manufacturing strain comprising a bacteriophage selected from a bacteriophage comprising a polynucleotide sequence having 85%-100% identity to a sequence of SEQ ID NO: 1-22.

190 . The bacterial host manufacturing strain of claim 189 , wherein the bacteriophage comprises a sequence having at least 90% sequence identity to a polynucleotide sequence of SEQ ID NO: 1-22.

191 . A method of treating a bacterial infection in a subject with cystic fibrosis comprising administering to the subject one or more distinct bacteriophages selected from a bacteriophage comprising a polynucleotide sequence having at least 90% identity to SEQ ID NO: 1, and SEQ ID NO: 3.

192 . The method of claim 191 , wherein the one or more distinct bacteriophages are selected from a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO: 3.

193 . The method of any of claims 191 - 192 , wherein the method comprises administering two or more of the bacteriophages.

194 . The method of any of claims 191 - 193 , wherein the method comprises the administration of three of the bacteriophages.

195 . The method of any of claims 191 - 194 , further comprising administering one or more bacteriophages comprising a polynucleotide sequence having at least 90% identity to SEQ ID NO:4 and SEQ ID NO:6.

196 . The method of any of claim 195 , wherein a bacteriophage comprising a polynucleotide sequence having at least 90% identity to SEQ ID NO:4 and a bacteriophage comprising a polynucleotide sequence having at least 90% identity to SEQ ID NO:6 are administered.

197 . The method of any of claims 195 - 196 , wherein the bacteriophages comprise a polynucleotide sequence of SEQ ID NO:4 and/or SEQ ID NO:6.

198 . A method of treating a bacterial infection in a subject with pneumonia comprising administering to the subject one of more distinct bacteriophages selected from a bacteriophage comprising a polynucleotide sequence having at least 90% identity to SEQ ID NO:1 and SEQ ID NO: 3.

199 . The method of claim 198 , wherein the one or more bacteriophages comprise a polynucleotide sequence of SEQ ID NO:1 and SEQ ID NO: 3.

200 . The method of any of any of claims 198 - 199 , comprising two bacteriophages.

201 . The method of any of claims 198 - 200 , further comprising at least one bacteriophage comprising a polynucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5 or SEQ ID NO: 8.

202 . The method of claim 201 , comprising a bacteriophage comprising a polynucleotide sequence having at least 90% sequence identity to SEQ ID NO: 5 and a bacteriophage comprising a polynucleotide sequence having at least 90% sequence identity to SEQ ID NO: 8.

203 . The method of any of claims 201 and 202 , wherein the bacteriophages have 100% sequence identity to the polynucleotide sequence.

204 . The method of any of claims 198 - 203 , further comprising a bacteriophage comprising a polynucleotide sequence having at least 90% identity to SEQ ID NO: 12.

205 . The method of claim 204 , comprising a bacteriophage comprising a polynucleotide sequence of SEQ ID NO: 12.

Assignments (8)