Loading patent…
AssigneeThe Children's Hospital of Philadelphia
InventorsMortimer PONCZ, Kandace GOLLOMP, Lubica RAUVO, Anna M. KOWALSKA
Estimating the term…
The present disclosure is directed to the use of PF4 alone or anti-PF4 antibodies alone or the combination thereof to treat sepsis. Neutrophils release their histone-coated DNA termed neutrophil extracellular traps (NETs) during sepsis and related inflammatory disorders. NETs are broken down and release NET degradation products (NDPs) like histone that are toxic and contribute to the morbidity and mortality in sepsis and related inflammatory disorders. The inventors have shown that a native platelet protein, platelet factor 4 (PF4), which is highly positively-charged, compacts NETs that are in turn highly negatively-charged. These compact NETs are resistant to NDP release and breakdown by circulating DNases. PF4 protects against this lysis and NDP release and improves outcome. The inventors also found that an antibody to PF4 that cross-binds PF4 on NETs further protects against lysis and NDP release. Such antibodies, perhaps supplemented with additional PF4, are therapeutic candidates for treatment of sepsis.
A method of treating a subject having or at risk of developing a neutrophil extracellular trap (NET) associated disease or syndrome comprising administering to said subject an antibody or fragment thereof that binds immunologically to NETs, to modified NETs, such as NETs complexed to platelet factor (PF4), wherein said antibody exhibits reduced binding to FcR and/or complement activation as compared to an unmodified antibody of the same class and isotype.
(canceled)
(canceled)
An antibody or antibody fragment that binds immunologically to platelet factor 4 (PF4), wherein said antibody exhibits reduced binding to FcR and/or complement activation as compared to an unmodified antibody of the same class and isotype.
(canceled)
23-25. (canceled)
A method of treating a subject having or at risk of developing a neutrophil extracellular trap (NET) associated disease or syndrome comprising administering to said subject platelet factor (PF4).
27-35. (canceled)
Dependencies are inferred from the claim text.