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Publication Number
US-9951104-B2
Publication Date
2018-04-24
Expiration Date
Abstract
We describe peptides and their uses for the treatment of autoimmune, inflammatory and metabolic diseases.
Core Innovation
The invention is a composition comprising a peptide consisting of the amino acid sequence [procedural detail omitted for safety] (SEQ ID NO: 1), identified as SP16, a short Serpin-derived peptide described as an anti-inflammatory and immunomodulatory agent. Compositions comprise the peptide alone or peptide fusions joined to epitope tags or half-life extenders. In cell assays, SP16 activates TLR2 in a dose-dependent manner, but not TLR4.
Preclinical evaluations associate SP16 and related peptides with reduced TNF-α in mouse inflammation and sepsis models, reduced paw swelling in a collagen antibody-induced arthritis model, improved glycemic measures in a type II diabetes model, and increased survival in lethal endotoxemia. SP16 reduces IL-1β-induced MMP1 secretion from primary human synoviocytes relative to a scrambled control. Alanine substitutions affect anti-inflammatory and TLR2 activity.
The background section is not included, so the problem being solved is not explicitly described in the patent content provided. Autoimmune, inflammatory, and metabolic conditions are identified as target fields, without elaboration on the limitations addressed. The abstract and summary sections are likewise not provided, and the partial content reports experimental outcomes only.
Claims Coverage
The claims cover compositions comprising the specified peptide and present three inventive features. The input descriptions differ on whether the peptide fusion is claimed as an independent claim or as a dependent addition to the peptide composition.
Composition comprising the defined peptide
An independent claim covers a composition comprising a peptide consisting of the amino acid sequence [procedural detail omitted for safety] (SEQ ID NO: 1).
Peptide fused to or combined with a second peptide or protein
The composition comprises the specified peptide with at least one second peptide or protein, which is an epitope tag, a half-life extender, or both. One description presents this as an independent claim for a peptide fusion, and another presents it as a dependent claim.
Pharmaceutically acceptable carrier
Dependent claims add a pharmaceutically acceptable carrier, with further claims specifying injectable and intravenous carrier forms.
The claim coverage centers on a composition comprising the specified peptide, with features adding a second peptide or protein (an epitope tag, a half-life extender, or both) and a pharmaceutically acceptable carrier, including injectable or intravenous forms.
Stated Advantages
Preclinical findings report reduced TNF-α and a survival benefit for SP16 in mouse inflammation and sepsis models, including increased survival in lethal endotoxemia.
SP16 reduced arthritis paw swelling comparably to dexamethasone in the collagen antibody-induced arthritis model, and lower arthritis scores are reported.
SP16 improved glycemic measures and glycemic control in diabetic mice.
SP16 reduced MMP1 secretion from human synoviocytes.
Documented Applications
Anti-inflammatory and immunomodulatory agent for autoimmune and inflammatory diseases, including rheumatoid arthritis.
Potential application in metabolic diseases, including type II diabetes.
Endotoxemia and sepsis, evaluated in mouse LPS inflammation and sepsis models with SP16 and related peptides.
Evaluation of SP16 in a collagen antibody-induced arthritis model.
Cell assays assessing TLR2 and TLR4 activation and MMP1 secretion from human synoviocytes.
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