Binding moieties for biofilm remediation
Inventors
Kauvar, Lawrence M. • RYSER, Stefan • Estelles, Angeles • Simon, Reyna J. • BAKALETZ, Lauren Opremcak • Goodman, Steven David
Assignees
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Abstract
Binding agents able to disrupt bacterial biofilms of diverse origin are described, including monoclonal antibodies secreted by human B lymphocytes. Methods to prevent formation of or to dissolve biofilms with these binding agents are also described. Immunogens for eliciting antibodies to disrupt biofilms are also described.
Core Innovation
The invention relates to monoclonal antibodies or antigen binding fragments that specifically bind DNA binding protein II (DNABII). The disclosed antibodies comprise defined heavy chain variable regions and light chain variable regions of TRL1068, TRL1330, or TRL1337, and the binding is directed to DNABII as an interaction partner in biofilms that include DNABII.
The disclosed concept addresses biofilm remediation by using antibody affinity to improve binding over DNABII protein affinity for a component of a biofilm that includes the DNABII protein. The claims also specify binding of DNABII proteins from at least three different bacterial species.
The disclosure further specifies antibody formats and construct features, including Fv antibodies, bispecific antibodies, chimeric antibodies, and complete antibodies. For complete antibodies, the complete antibody comprises generic constant regions heterologous to the variable regions, and the invention is disclosed in connection with pharmaceutical or veterinary compositions comprising the mAb as an active ingredient and a suitable pharmaceutical excipient.
Claims Coverage
The independent claims cover mAbs or antigen binding fragments that specifically bind DNABII with particular TRL1068, TRL1330, and/or TRL1337 heavy/light variable region sets, and further recite selectable antibody formats and, in dependents, performance constraints including comparative affinity and cross-species breadth. Across the claims, the inventive coverage includes specified variable-region sets, DNABII binding breadth, comparative affinity relative to biofilm-component binding, complete-antibody constant-region heterology, and composition formats.
Specific TRL1068, TRL1330, or TRL1337 variable regions for DNABII binding
A monoclonal antibody or antigen binding fragment thereof that specifically binds DNA binding protein II (DNABII), wherein the mAb or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region corresponding to TRL1068, or to TRL1330, or to TRL1337.
DNABII binding across at least three bacterial species
The mAb or antigen binding fragment binds a DNABII protein from at least three different bacterial species.
Affinity exceeding DNABII binding of a biofilm component
The mAb or antigen binding fragment thereof has an affinity that exceeds an affinity of the DNABII protein for a component of a biofilm that includes the DNABII protein.
Complete antibody with generic constant regions heterologous to the variable regions
The complete antibody comprises generic constant regions heterologous to the variable regions thereof.
Fv, bispecific, chimeric, or complete antibody formats
The mAb or antigen binding fragment thereof is an Fv antibody, a bispecific antibody, a chimeric antibody, or a complete antibody.
Pharmaceutical or veterinary composition with excipient
A pharmaceutical or veterinary composition comprises as an active ingredient the mAb or antigen binding fragment thereof and a suitable pharmaceutical excipient.
Overall, the claims cover DNABII-targeted mAbs or antigen binding fragments defined by particular TRL1068, TRL1330, or TRL1337 heavy and light variable regions, with optional antibody formats and, for complete antibodies, generic constant regions heterologous to the variable regions. Dependent claim refinements add binding to DNABII from at least three bacterial species and affinity exceeding DNABII’s affinity for a biofilm component containing DNABII. The invention is also covered in pharmaceutical or veterinary composition embodiments with an excipient.
Stated Advantages
The mAb or antigen binding fragment has an affinity that exceeds an affinity of the DNABII protein for a component of a biofilm that includes the DNABII protein.
The mAb binds a DNABII protein from at least three different bacterial species.
Documented Applications
Not explicitly described in patent.
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