Lysin polypeptides active against Gram-negative bacteria
Inventors
Schuch, Raymond • Hoffenberg, Simon • Wittekind, Michael
Assignees
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Publication Number
US-11413334-B2
Publication Date
2022-08-16
Expiration Date
Abstract
The present disclosure provides methods and compositions useful for the prophylactic and therapeutic amelioration and treatment of infections caused by Gram-negative bacteria, including Pseudomonas aeruginosa. The disclosure further provides compositions and methods of incorporating and utilizing lysin polypeptides of the present disclosure for augmenting the efficacy of antibiotics generally suitable for the treatment of Gram-negative bacterial infection.
Core Innovation
The patent describes lysin polypeptides and fragments having lytic activity directed to Gram-negative bacteria. The lysin polypeptides include amino acid sequences that are at least 90% identical to polypeptide sequences selected from SEQ ID NO: 3, SEQ ID NO: 7, and SEQ ID NO: 8, and are used to inhibit the growth, reduce an initial population, or kill Gram-negative bacteria.
The document frames a need to treat bacterial infections caused by one or more species of Gram-negative bacteria, including pathogenic Gram-negative bacterial infections in a subject. The disclosed approaches include administering lysin-containing compositions to subjects diagnosed with, at risk for, or exhibiting symptoms of Gram-negative bacterial infections, where the lysin polypeptide or fragment has the property of inhibiting the growth, reducing an initial population, or killing the Gram-negative bacteria.
The patent further discloses combination approaches in which lysin polypeptides are co-administered with antibiotics suitable for treatment of Gram-negative bacterial infection. The combinations are stated to be more effective at inhibiting growth, reducing an initial population, or killing Gram-negative bacteria than administration of either agent alone, and the document also describes topical and systemic treatment of pathogenic bacterial infections.
Claims Coverage
The independent claims are clm-00001, clm-00002, clm-00007, clm-00008, and clm-00010. Across these claims, the coverage centers on five inventive features: SEQ ID lysins, treating Gram-negative infection, topical or systemic treatment, co-administering with an antibiotic, and augmenting antibiotic efficacy.
SEQ ID lysins
Lysin polypeptides having an amino acid sequence at least 90% identical to a polypeptide sequence selected from SEQ ID NO: 3, SEQ ID NO: 7, and SEQ ID NO: 8, or fragments thereof having lytic activity, wherein the lysin polypeptide or fragment has the property of inhibiting the growth, reducing an initial population, or killing at least one species of Gram-negative bacteria.
Treating Gram-negative infection
A method of treating a bacterial infection caused by one or more species of Gram-negative bacteria by administering to a subject diagnosed with, at risk for, or exhibiting symptoms of a bacterial infection a composition comprising an effective amount of a lysin polypeptide or fragment having lytic activity and the property of inhibiting the growth, reducing an initial population, or killing one or more species of Gram-negative bacteria.
Topical or systemic treatment
A method of treating a topical or systemic pathogenic bacterial infection caused by one or more species of Gram-negative bacteria by administering to a subject a composition containing an effective amount of a lysin polypeptide or fragment having lytic activity and the property of inhibiting the growth, reducing an initial population, or killing one or more species of Gram-negative bacteria.
Co-administering with an antibiotic
A method of preventing or treating a Gram-negative bacterial infection comprising co-administering to a subject diagnosed with, at risk for, or exhibiting symptoms of a Gram-negative bacterial infection a first effective amount of a composition comprising a lysin polypeptide or fragment and a second effective amount of an antibiotic suitable for the treatment of Gram-negative bacterial infection.
Augmenting antibiotic efficacy
A method for augmenting the efficacy of an antibiotic suitable for the treatment of Gram-negative bacterial infection by co-administering the antibiotic in combination with one or more lysin polypeptides or fragments, wherein administration of the combination is more effective in inhibiting the growth, reducing an initial population, or killing the Gram-negative bacteria than administration of either the antibiotic or the lysin polypeptide or fragment individually.
Across the independent claims, the patent’s claimed subject matter focuses on lysin polypeptides or enzymatically lytic fragments with at least 90% sequence identity to SEQ ID NO: 3, SEQ ID NO: 7, or SEQ ID NO: 8 that produce specific antibacterial outcomes against Gram-negative bacteria, including methods of contacting bacteria, treating infections in a subject, topical or systemic treatment, and co-administering with antibiotics where the combination is more effective than either agent alone.
Stated Advantages
Inhibiting the growth of Gram-negative bacteria.
Reducing an initial population of Gram-negative bacteria.
Killing Gram-negative bacteria.
Providing more effective inhibition or killing than administration of either the antibiotic or the lysin polypeptide or fragment individually when co-administered.
Documented Applications
Methods of inhibiting the growth, reducing the population, or killing at least one species of Gram-negative bacteria by contacting bacteria with a lysin-containing composition.
Treatment of a bacterial infection caused by one or more species of Gram-negative bacteria in a subject diagnosed with, at risk for, or exhibiting symptoms of infection.
Topical or systemic treatment of a pathogenic bacterial infection caused by one or more species of Gram-negative bacteria.
Preventing or treating a Gram-negative bacterial infection by co-administering a lysin composition and an antibiotic suitable for Gram-negative bacterial infection.
Augmenting the efficacy of an antibiotic suitable for treatment of Gram-negative bacterial infection by co-administering the antibiotic with lysin polypeptides or lytic fragments.
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