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US 10,682,399 B2Granted
Target peptides for colorectal cancer therapy and diagnostics
AssigneesThe University of Birmingham, University of Virginia Patent Foundation
InventorsDonald F. Hunt, Jeffrey Shabanowitz, Jennifer G. Abelin, Mark Cobbold, Sarah Amy Penny
Life of this patent
Estimating the term…
Abstract
A set of target peptides are presented by HLA A*0201, B*0301, B*0702 and B*2705 on the surface of disease cells. They are envisioned to, among other things, stimulate an immune response to the proliferative disease, e.g., colorectal cancer, to function as immunotherapeutics in adoptive T cell therapy or as a vaccine, facilitate antibody recognition of tumor boundaries in surgical pathology samples, act as biomarkers for early detection and/or diagnosis of the disease, and/or act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.
Claims101
A composition comprising:
- (a) at least one synthetic target peptide, wherein each synthetic target peptide:
- (i) is 8 to 50 amino acids long;
- and
- (ii) comprises an amino acid sequence selected from the group consisting of:
- SEQ ID NO:
- 3, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 5, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 6, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 7, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 12, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 13, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 14, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 15, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 20, wherein the threonine at the fifth position is phosphorylated or replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 22, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 24, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 26, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 28, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 29, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 30, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 31, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 32, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 33, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 34, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 43, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 48, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 49, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 50, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 52, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 54, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 56, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 61, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 63, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 67, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 68, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 71, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 72, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 73, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 81, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 85, wherein the serine at the seventh position of is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 87, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 91, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 93, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 94, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 95, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine, the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine, or any combination thereof;
- SEQ ID NO:
- 96, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 99, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 100, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 101, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 103, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 104, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 105, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 106, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 108, wherein the serine at the seventh position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 109, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 110, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 114, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 117, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 119, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine and the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 123, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 126, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 128, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 129, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 131, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 132, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 135, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 140, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 141, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 143, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 144, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 146, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 147, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 148, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 149, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 150, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 154, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 155, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 157, wherein the serine at the fourth position of is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 158, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 159, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 160, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 161, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 162, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 164, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 165, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 167, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 170, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 172, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 173, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 174, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 176, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;
- and
- SEQ ID NO:
- 177, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine, and
- (b) a therapeutically effective amount of an adjuvant.
177 more elements
A composition comprising a synthetic target peptide, wherein the synthetic target peptide:
- is 8 to 50 amino acids long;
- and
- (ii) comprises an amino acid sequence selected from the group consisting of:
- SEQ ID NO:
- 3, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 5, wherein the serine at the third position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 6, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 7, wherein the threonine at the fourth position is replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 12, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 13, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 14, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 15, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 20, wherein the threonine at the fifth position is replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 22, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 24, wherein the serine at the fifth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 26, wherein the serine at the eighth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 28, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 29, wherein the serine at the fifth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 30, wherein the serine at the third position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 31, wherein the serine at the fifth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 32, wherein the serine at the eighth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 33, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 34, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 43, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 48, wherein the serine at the eighth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 49, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 50, wherein the serine at the ninth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 52, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 54, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 56, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 61, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 63, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 67, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 68, wherein the serine at the ninth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 71, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 72, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 73, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 81, wherein the serine at the ninth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 85, wherein the serine at the seventh position of is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 87, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 91, wherein the serine at the eighth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 93, wherein the serine at the eighth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 94, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 95, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine, the serine at the eighth position is replaced with a mimetic of phosphoserine, or any combination thereof;
- SEQ ID NO:
- 96, wherein the threonine at the fourth position is replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 99, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 100, wherein the threonine at the sixth position is replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 101, wherein the threonine at the sixth position is replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 103, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 104, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 105, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 106, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 108, wherein the serine at the seventh position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 109, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 110, wherein the threonine at the fourth position is replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 114, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 117, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 119, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine and the serine at the eighth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 123, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 126, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 128, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 129, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 131, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 132, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 135, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 140, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 141, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 143, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 144, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 146, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 147, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 148, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 149, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 150, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 154, wherein the serine at the third position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 155, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 157, wherein the serine at the fourth position of is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 158, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 159, wherein the serine at the eighth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 160, wherein the serine at the fifth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 161, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 162, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 164, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 165, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 167, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 170, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 172, wherein the threonine at the fourth position is replaced with a mimetic of phosphothreonine;
- SEQ ID NO:
- 173, wherein the serine at the fifth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 174, wherein the serine at the sixth position is replaced with a mimetic of phosphoserine;
- SEQ ID NO:
- 176, wherein the serine at the fourth position is replaced with a mimetic of phosphoserine;
- and
- SEQ ID NO:
- 177, wherein the threonine at the sixth position is replaced with a mimetic of phosphothreonine.
175 more elements
Dependencies are inferred from the claim text.