Monoclonal antibody and vaccine targeting filamentous bacteriophage

Inventors

Bollyky, Paul L. • Parks, William • Secor, Patrick

Assignees

Inimmune Corp • Inimmune Corp

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Publication Number

US-11911472-B2

Patent

Publication Date

2024-02-27

Expiration Date


Abstract

Described here is a method for reducing or preventing Pseudomonas aeruginosa biofilm formation in a human subject in need thereof, comprising administering to the human subject a first composition comprising (a) an antigen-binding polypeptide that binds Pf-family bacteriophage, or (b) a vaccine against Pf-family bacteriophage. Also described is an antigen-binding polypeptide that binds specifically to a CoaB protein of Pf-family bacteriophage or fragment thereof.

Core Innovation

The patent relates to vaccine and therapeutic approaches targeting Pf-family filamentous bacteriophage Pf4/CoaB to prevent or reduce Pseudomonas aeruginosa biofilm formation and to improve antibiotic susceptibility. A central target is the CoaB coat protein, including a CoaB fragment consisting of the amino acid sequence GVIDTSAVESAITDGQGDM (SEQ ID NO:1).

The disclosed approaches include antigen-binding polypeptides that disrupt Pf4-associated biofilm organization, including antibodies that bind CoaB and antiserum derived from vaccination. The patent describes disruption of Pf4 tactoidal/crystalline biofilm organization and changes consistent with altered biofilm matrix organization, including reduced birefringence/liquid crystal features.

The patent further describes vaccine formulations using immunogenic CoaB fragments conjugated to an immunogenic protein and a pharmaceutically acceptable carrier. It also describes supported embodiments where antiserum and monoclonal antibodies alter antibiotic tolerance and can facilitate antibiotic penetration.

Claims Coverage

The partial content provides one independent claim, with the inventive features focused on producing antiserum containing CoaB-specific antibodies by immunization using a defined Pf-family bacteriophage vaccine component and a pharmaceutically acceptable carrier. The claim includes three main inventive feature elements.

CoaB fragment conjugate in Pf-family bacteriophage vaccine

An immunizing vaccine against the Pf-family bacteriophage comprising an immunogenic fragment of the CoaB coat protein consisting of the amino acid sequence GVIDTSAVESAITDGQGDM (SEQ ID NO:1) conjugated to an immunogenic protein.

Pharmaceutically acceptable carrier for vaccination

A vaccine against the Pf-family bacteriophage comprising a pharmaceutically acceptable carrier.

Immunization to make CoaB-specific antiserum

A method of making an antiserum containing antibodies specific to a CoaB coat protein of the Pf-family bacteriophage by immunizing an animal or human subject with the Pf-family bacteriophage vaccine.

Overall, the claim scope centers on generating antiserum containing antibodies specific to the Pf-family bacteriophage CoaB coat protein via immunization with the specified SEQ ID NO:1 CoaB fragment conjugated to an immunogenic protein and formulated with a pharmaceutically acceptable carrier.

Stated Advantages

Prevents or reduces Pseudomonas aeruginosa biofilm formation.

Improves antibiotic susceptibility.

Alters antibiotic tolerance.

Antibody-facilitated antibiotic penetration.

Disrupts Pf4 tactoidal/crystalline biofilm organization and reduces birefringence/liquid crystal features.

Documented Applications

Vaccine and therapeutic targeting of Pf-family bacteriophage Pf4/CoaB for preventing or reducing Pseudomonas aeruginosa biofilm formation and improving antibiotic susceptibility.

Use in producing antiserum containing antibodies specific to the CoaB coat protein via immunizing an animal or human subject with a Pf-family bacteriophage vaccine.

Use of antibody-based approaches, including antiserum and monoclonal antibodies, to change biofilm matrix organization and support improved antibiotic outcomes.

Vaccine formulations using immunogenic CoaB fragments conjugated to an immunogenic protein and administered with a pharmaceutically acceptable carrier.

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