Defined dose therapeutic phage
First Claim
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1. A method of making a non-replicating anti-bacterial phage, said method comprising the step of producing said anti-bacterial phage in a host production bacterium, wherein said anti-bacterial phage is unable to replicate in a target bacterium and wherein said anti-bacterial phage inhibits growth of said target bacterium.
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Abstract
The invention provides therapeutic, defined-dose anti-bacterial phage preparations, methods to make such preparations, methods to treat bacterial infections using such preparations and methods to diagnose bacterial infections using such preparations.
9 Citations
25 Claims
- 1. A method of making a non-replicating anti-bacterial phage, said method comprising the step of producing said anti-bacterial phage in a host production bacterium, wherein said anti-bacterial phage is unable to replicate in a target bacterium and wherein said anti-bacterial phage inhibits growth of said target bacterium.
- 5. A pharmaceutical composition comprising an anti-bacterial phage, wherein said anti-bacterial phage inhibits growth of a target bacterium, and wherein said anti-bacterial phage has diminished replication activity in said target bacterium.
- 9. A pharmaceutical composition comprising a genetically incompetent anti-bacterial phage, wherein said anti-bacterial phage inhibits growth of a target bacterium.
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13. A method of identifying an anti-bacterial phage that is unable to replicate in a selected target bacterium, said method comprising the steps of:
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culturing said target bacterium; and
testing various potential anti-bacterial phage, including genetic variants of a phage, for combined properties of inhibition of growth on said target bacterium, and absence of capacity to replicate phage DNA or phage in said target bacterium. - View Dependent Claims (14)
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15. A method of producing non-replicating anti-bacterial phage comprising the steps of:
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replicating phage in a host production bacterium, harvesting said phage from said host production bacterial culture, and removing substantially all of the function of the nucleic acids from said phage, thereby producing said non-replicating anti-bacterial phage. - View Dependent Claims (16)
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17. A method of making a defined dose anti-bacterial phage that kills a defined target bacterium, said method comprising producing said anti-bacterial phage in:
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a host production bacterium and isolating tail portions separate from DNA containing heads;
a host production bacterium and inactivating nucleic acid of said phage, e.g., by nicking, fragmenting, crosslinking, or chemically modifying said nucleic acid;
a host production bacterium and harvesting components temporally before substantial assembly of complete phage;
a complementing host production bacterium where said anti-bacterial phage would not replicate in said target bacterium;
a host production bacterium comprising a helper phage where said anti-bacterial phage would not replicate in said target bacterium;
ora permissive production host which phage are non-permissive for replication in target bacterium in a different condition, e.g., temperature. - View Dependent Claims (18, 19)
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- 20. A defined dose therapeutic anti-bacterial composition comprising a phage protein derived from an intact parental phage or prophage, said anti-bacterial composition capable of killing a target bacterium, said anti-bacterial composition exhibiting less than 20% DNA or phage replication activity in said target bacterium, when compared to said intact parental phage or prophage.
- 24. A therapeutic anti-bacterial composition comprising a genetically incompetent phage wherein said phage kills a target bacterium.
Specification