Decreasing Staphylococcus aureus infections in colonized patients
Inventors
ESSER, Mark • RUZIN, Alexey • JAFRI, Hasan • SHOEMAKER, Kathryn • Sellman, Bret • Yu, Li
Assignees
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Publication Number
US-12264194-B2
Publication Date
2025-04-01
Expiration Date
Abstract
The present disclosure is directed to methods of treating subjects colonized with S aureus with an anti-alpha toxin antibody or antigen-binding fragment thereof. The methods can decrease the incidence of infection attendant to the presence of S. aureus in the subject.
Core Innovation
The invention relates to treating a subject colonized with Staphylococcus aureus (S. aureus) by administering an antibody or antigen-binding fragment that binds to S. aureus alpha toxin (AT). Polymerase chain reaction (PCR) is used to detect the level of S. aureus in a sample obtained from the subject prior to administering the antibody or antigen-binding fragment, and the sample is limited to a level that does not exceed a level that correlates to a PCR cycle threshold (Ct) value of 29 or above.
The method specifies that Ct 29 corresponds to a sample concentration that does not exceed 1700 colony forming units (CFU)/mL of S. aureus. The antibody or antigen-binding fragment that binds to S. aureus AT comprises defined VH and VL complementarity determining region amino acid sequences.
The disclosure ties PCR-based patient or sample assessment to treating colonized subjects using anti–S. aureus alpha toxin antibodies or antigen-binding fragments, including suvratoxumab/MEDI4893. The document emphasizes rapid PCR quantification in pre-dose samples, including Ct thresholding, and PCR target selection such as S. aureus protein A (spa) and MRSA determinants (mecA/SCCmec) in the described contexts.
Claims Coverage
The independent claim is clm-00001. It contains the core inventive concept of administering an anti–S. aureus alpha toxin antibody or antigen-binding fragment while using pre-dose PCR quantification to ensure the subject’s colonization level does not exceed a Ct/CFU correlation threshold. Dependent claims add narrower limitations to the antibody format, Fc features, and PCR detection target and specimen context.
Anti–S. aureus alpha toxin antibody defined by VH and VL CDR sequences
Administering an antibody or antigen-binding fragment that binds to S. aureus alpha toxin (AT), wherein the antibody or antigen-binding fragment comprises a VH CDR1 with SEQ ID NO: 1, VH CDR2 with SEQ ID NO:2, VH CDR3 with SEQ ID NO:3, VL CDR1 with SEQ ID NO:4, VL CDR2 with SEQ ID NO:5, and VL CDR3 with SEQ ID NO:6.
PCR-verified colonization level threshold before administration
Using polymerase chain reaction (PCR) to detect the level of S. aureus in a sample obtained from the subject prior to administering the antibody or antigen-binding fragment, wherein the sample has a level of S. aureus that does not exceed a level that correlates to a PCR cycle threshold (Ct) value of 29 or above, and wherein PCR Ct value of 29 corresponds to a sample concentration of S. aureus that does not exceed 1700 CFU/mL.
Administering to a subject colonized with Staphylococcus aureus
Treating a subject colonized with Staphylococcus aureus (S. aureus) by administering the antibody or antigen-binding fragment that binds to S. aureus alpha toxin (AT).
Claim coverage centers on selecting colonized subjects for anti–S. aureus alpha toxin antibody treatment using pre-dose PCR cycle threshold criteria that correlate to a maximum CFU/mL level, combined with an antibody or antigen-binding fragment defined by specific VH and VL CDR amino acid sequences. Dependent claims further narrow the antibody characteristics and refine PCR targets and sample context.
Stated Advantages
Greater efficacy in subgroups with low colonization (Ct ≤ 29).
Safety benefits are reported in the described context.
Health-resource utilization benefits are reported in the described context.
Documented Applications
Treatment or prevention of Staphylococcus aureus infections in colonized patients by administering anti–S. aureus alpha toxin antibodies or antigen-binding fragments with PCR-based pre-dose guidance.
Clinical trial context for mechanically ventilated ICU patients, including sample types such as endotracheal aspirate and bronchial or tracheal samples, with measurements described as clinical, microbiological, and radiographic measures.
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