Peptides having anti-inflammatory properties
Inventors
Jaynes, Jesse • Lopez, Henry Wilfred • Martin, George R. • YATES, Clayton • Garvin, Charles
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Assignees
Member
Riptide BioscienceRiptide Bioscience develops engineered peptides derived from host defense peptides found widely in nature. Their focus is on creating peptide-based therapeutics for cancer, inflammatory diseases, and microbial infections, especially those resistant to conventional treatments. The company advances both preclinical and early-stage clinical programs, collaborates with academic partners and government agencies, and holds patents for its engineered peptide design technologies.
Riptide Bioscience develops engineered peptides derived from host defense peptides found widely in nature. Their focus is on creating peptide-based therapeutics for cancer, inflammatory diseases, and microbial infections, especially those resistant to conventional treatments. The company advances both preclinical and early-stage clinical programs, collaborates with academic partners and government agencies, and holds patents for its engineered peptide design technologies.
Publication Number
US-10149886-B2
Publication Date
2018-12-11
Expiration Date
Abstract
Aspects of the present invention relate to peptides having anti-inflammatory activity, compositions containing one or more of the peptides, and use of the peptides to treat conditions associated with excessive inflammation in animals, particularly humans and other mammals.
Core Innovation
Aspects of the present invention relate to peptides having anti-inflammatory activity, compositions containing one or more of the peptides, and use of the peptides to treat conditions associated with excessive inflammation in animals, particularly humans and other mammals. The present invention is based, in part, on the discovery of novel peptides that have powerful anti-inflammatory activities in vitro and in vivo, and that specifically bind to key functional regions on one or more signaling proteins, particularly pro-inflammatory cytokines, macrophage inhibition proteins, and histone regulation proteins.
In one aspect, the invention provides a composition comprising an anti-inflammatory polypeptide. In certain embodiments, the anti-inflammatory polypeptide is 3 to 24 amino acids residues in length and includes a striapathic region consisting of alternating hydrophobic and hydrophilic modules. The Structural Algorithm requires an anti-inflammatory peptide to have a length of 3 to 24 amino acid residues, a striapathic region that comprises at least 25% of the length of the polypeptide, and at least one anti-inflammatory property.
Under normal conditions, inflammation helps an animal recover from injury, but various agents can cause prolonged and excessive inflammation known as chronic inflammation. Chronic inflammation is believed to be a contributing factor to many widespread and debilitating diseases, and despite growing knowledge, treatments for such conditions remain elusive and many anti-inflammatory therapies are associated with harmful side effects, creating a critical need to identify therapeutic agents that reduce inflammation without harmful side effects.
Claims Coverage
Two independent claims were identified, each defining an immunomodulatory peptide with specific sequence-format or specific sequences.
Immunomodulatory peptide defined by specific modular formulae
An immunomodulatory peptide of 18 amino acid residues or less in length, wherein the peptide has a sequence defined by one of the formulae: [Y1aY1b]-[X1aX1b]-[Y2aY2b]-[X2aX2b]-[Y3a]-[X3a]; and [X3a]-[Y3a]-[X2bX2a]-[Y2bY2a]-[X1bX1a]-[Y1bY1a]; wherein: Y1a, Y1b, Y2a, Y2b and Y3a are each phenylalanine; and X1a, X1b, X2a, X2b and X3a are each independently selected from lysine and arginine.
Immunomodulatory peptide comprising specified sequences
An immunomodulatory peptide of 18 amino acid residues or less in length, the peptide comprising the amino acid sequence KFKKAFKKAF (SEQ ID NO:148) or FFRKFAKRFK (SEQ ID NO:122).
The independent claims cover (1) peptides defined by alternating module formulae with hydrophobic phenylalanine modules and hydrophilic lysine/arginine modules within an 18-residue limit, and (2) specific 10-residue immunomodulatory peptide sequences KFKKAFKKAF and FFRKFAKRFK.
Stated Advantages
Peptides have powerful anti-inflammatory activities in vitro and in vivo.
Peptides specifically bind to key functional regions on one or more signaling proteins, particularly pro-inflammatory cytokines, macrophage inhibition proteins, and histone regulation proteins.
Peptides are sufficiently stable in the circulation to allow for intravenous administration.
There remains a critical need for therapeutic agents that reduce inflammation without harmful side effects (problem the invention addresses).
Documented Applications
Use of the peptides to treat conditions associated with excessive inflammation in animals, particularly humans and other mammals.
Methods of treating subjects by administering a composition comprising an anti-inflammatory polypeptide for subjects having elevated levels of inflammatory cytokines, suffering from a chronic inflammatory condition, or likely to develop a chronic inflammatory condition.
Treatment of chronic inflammatory conditions including irritable bowel disease, ulcerative colitis, colitis, Crohn's disease, fibrosis, idiopathic pulmonary fibrosis, asthma, keratitis, arthritis, osteoarthritis, rheumatoid arthritis, autoimmune diseases, FIV or HIV infection, and cancer.
Treatment of cancer, with cancers explicitly listed including colon cancer, breast cancer, leukemia, lymphoma, ovarian cancer, prostate cancer, liver cancer, lung cancer, testicular cancer, cervical cancer, bladder cancer, endometrial cancer, kidney cancer, melanoma, and cancers of the thyroid or brain.
Treatment of fibrosis, including pulmonary fibrosis, dermal fibrosis, hepatic fibrosis, renal fibrosis, and fibrosis caused by ionizing radiation.
Administration of compositions in combination with a chemotherapeutic agent, immunotherapeutic agent, and/or radiation therapy.
Pharmaceutical compositions comprising an anti-inflammatory polypeptide and a pharmaceutically acceptable carrier, including compositions substantially free of blood proteins and/or metabolites and compositions that include serum albumin (e.g., human serum albumin).
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