Synthetic peptides and methods of use for autoimmune disease therapies
AssigneePresident and Fellows of Harvard College
InventorsJack L. Strominger, Masha Fridkis-Hareli
Life of this patent
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Abstract
The invention provides peptide compositions, and methods of making and using therapeutic compositions for treatment of a subject for an autoimmune or an inflammatory disease. The invention also provides kits for assaying binding of a composition to a water-soluble MHC protein.
Claims26
A synthetic peptide comprising at least seven amino acid residues in length and capable of binding to an MHC class II protein associated with an autoimmune disease, the synthetic peptide binding with greater affinity to the antigen binding groove of the MHC class II protein than a type II collagen 261-273 peptide, wherein the synthetic peptide comprises a sequence selected from the group consisting of alanine-glutamic acid-lysine-tyrosine-alanine (AEKYA;
- SEQ ID NO:
- 39), alanine-glutamic acid-lysine-valine-alanine (AEKVA;
- SEQ ID NO:
- 40), alanine-glutamic acid-lysine-phenylalanine-alanine (AEKFA;
- SEQ ID NO:41), alanine-lysine-tyrosine-alanine-glutamic acid (AKYAE;
- SEQ ID NO:
- 54), glutamic acid-alanine-lysine-tyrosine-alanine (EAKYA;
- SEQ ID NO:
- 55), alanine-lysine-valine-alanine-glutamic acid (AKVAE;
- SEQ ID NO:
- 56), and glutamic acid-alanine-lysine-valine-alanine (EAKVA;
- SEQ ID NO:
- 57), alanine-lysine-phenylalanine-alanine-glutamic acid (AKFAE;
- SEQ ID NO:
- 58), and glutamic acid-alanine-lysine-phenylalanine-alanine (EAKFA;
- SEQ ID NO:
- 59).
A composition comprising a synthetic peptide having therapeutic activity in a subject suffering from an autoimmune disease selected from the group consisting of an arthritic condition and a demyelinating condition, wherein the peptide has an amino acid sequence having at least one of each of amino acids glutamic acid, lysine, and alanine and an amino acid selected from the group consisting of tyrosine, valine, and phenylalanine, the peptide having high affinity for an MHC class II protein selected from the group consisting of MHC class II DR-1, DR-2, and DR-4.
An isolated peptide composition having an amino acid sequence selected from the group consisting of:
- AKEYAAAAAAKAAAA (SEQ ID NO:
- 7), AAEYAAAAAAKAAAA (SEQ ID NO:
- 12), AAKYAEAAAAKAAAA (SEQ ID NO:
- 15), and EAKYAAAAAAKAAAA (SEQ ID NO:
- 18).
An isolated peptide composition having an amino acid sequence selected from the group consisting of:
- AEKYAAAAAAKAAAA (SEQ ID NO:
- 6), AKEYAAAAAAKAAAA (SEQ ID NO:
- 7), KEAYAAAAAAKAAAA (SEQ ID NO:
- 10), AEEYAAAAAAKAAAA (SEQ ID NO:
- I 1), AAEYAAAAAAKAAAA (SEQ ID NO:
- 12), EKAYAAAAAAKAAAA (SEQ ID NO:
- 13), AAKYEAAAAAKAAAA (SEQ ID NO:
- 14), AAKYAEAAAAKAAAA (SEQ ID NO:
- 15), EAAYAAAAAAKAAAAA (SEQ ID NO:
- 16), EKKYAAAAAAKAAAA (SEQ ID NO:
- 17), EAKYAAAAAAKAAAA (SEQ ID NO:
- 18), AKKYEAAAAAAAAAA (SEQ ID NO:
- 21), AAEYKAAAAAAAAAA (SEQ ID NO:
- 26), AAKYEAAAAAAAAAA (SEQ ID NO:
- 28), AAKYAEAAAAAAAAA (SEQ ID NO:
- 29), AEYAKAAAAAAAAAA (SEQ ID NO:
- 32), AEKAYAAAAAAAAAA (SEQ ID NO:
- 33), AYKAEAAAAAAAAAA (SEQ 20 ID NO:
- 35), and AKYAEAAAAAAAAAA (SEQ ID NO:
- 36).
An isolated peptide composition having an amino acid sequence capable of inhibiting an immune response in a subject to an autoantigen, wherein a position in the amino acid sequence of the peptide that corresponds to an antigen binding pocket in a peptide binding groove of an MHC class II DR protein is identified as a particular amino acid.
Dependencies are inferred from the claim text.