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Publication Number
US-10406100-B2
Publication Date
2019-09-10
Expiration Date
Abstract
This invention relates to a method for treating or preventing a disease by raising an innate immune response in a subject, the method comprising administering to the subject an effective amount of a composition comprising a TLR2 moiety in solution, wherein the TLR2 moiety comprises a TLR2 agonist and wherein the disease is not treated or prevented by a humoral or cellular immune response directed against the TLR2 moiety.
Core Innovation
The invention relates to a method for treating or minimizing the progression of a respiratory condition associated with one or more bacterial infectious agents in a subject by administering to the respiratory tract a composition comprising a soluble TLR2 moiety. The soluble TLR2 moiety comprises a TLR2 agonist and a solubilizing agent that increases the solubility of the TLR2 agonist in polar or aqueous solvents.
The soluble TLR2 moiety is presented such that it does not raise an immune response in the subject that is specific for an antigen of the one or more infectious agents, and the composition does not contain a peptide antigen comprising a T-helper epitope. The invention focuses on a non-antigen-specific innate immune response via TLR2 agonist delivery while avoiding antigen-specific immune responses directed to infectious-agent antigens and avoiding peptide antigen/T-helper epitope components.
The solubilizing agent comprises polyethyleneglycol (PEG), and the soluble TLR2 moiety is further characterized as a composition comprising a TLR2 agonist and PEG. In some embodiments, the method provides prophylactic and therapeutic activity for respiratory disease contexts such as influenza A and Legionella pneumophila.
Claims Coverage
The identified independent claim is directed to a method for treating or minimizing the progression of a respiratory condition associated with one or more bacterial infectious agents by administering to the respiratory tract a soluble TLR2 moiety formulation that increases solubility in polar or aqueous solvents. Across the claims, the inventive features are focused on avoiding antigen-specific immune responses, specifying PEG as the solubilizing agent, specifying the nature of the TLR2 agonist, and narrowing delivery and exclusion limitations such as intranasal administration and exclusion of TLR9 agonist administration.
Soluble TLR2 moiety for respiratory treatment
Administering to the respiratory tract a composition comprising a soluble TLR2 moiety comprising a TLR2 agonist and a solubilizing agent that increases the solubility of the TLR2 agonist in polar or aqueous solvents, thereby treating or minimizing the progression of the respiratory condition in the subject.
Avoiding antigen-specific immune response
Wherein the moiety does not raise an immune response in the subject that is specific for an antigen of the one or more infectious agents.
PEG solubilizing agent
Wherein the solubilizing agent comprises polyethyleneglycol (PEG).
No T-helper epitope peptide antigen
Wherein the composition does not contain a peptide antigen comprising a T-helper epitope.
PEG-Pam2Cys soluble TLR2 moiety
The method further specifies that the soluble TLR2 moiety is PEG-Pam2Cys.
Specific TLR2 agonist selection
The method is characterized by using a TLR2 agonist chosen from Pam2Cys, Pam3Cys, S-[2,3-bis(stearoyloxy) propyl] cysteine, S-[2,3-bis(lauroyloxy) propyl] cysteine, or S-[2,3-bis(octanoyloxy) propyl] cysteine.
Conjugated soluble TLR2 moiety
The method includes a soluble TLR2 moiety formed by conjugating a TLR2 agonist to a solubilizing agent.
Intranasal administration to the respiratory tract
The method further specifies that the composition is administered intranasally to a subject.
Excluding TLR9 agonist administration
The method excludes administering a TLR9 agonist.
Overall, the claim set centers on delivering a soluble TLR2 moiety consisting of a TLR2 agonist with a PEG solubilizing agent to the respiratory tract, while avoiding immune responses specific for infectious-agent antigens and avoiding compositions containing a peptide antigen with a T-helper epitope. Dependent features further narrow the composition to PEG-Pam2Cys or specified TLR2 agonists, characterize solubility via PEG, and narrow delivery and exclusion by specifying intranasal administration and excluding TLR9 agonist administration in some embodiments.
Stated Advantages
Treating or minimizing the progression of a respiratory condition in a subject associated with one or more bacterial infectious agents.
The moiety does not raise an immune response in the subject that is specific for an antigen of the one or more infectious agents.
The composition does not contain a peptide antigen comprising a T-helper epitope.
Documented Applications
Prophylactic and therapeutic activity for respiratory disease contexts including influenza A and Legionella pneumophila.
Treatment or progression-minimization in a subject for respiratory conditions associated with one or more bacterial infectious agents, with examples including influenza A and Legionella pneumophila described in the provided content.
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