IL-23 RECEPTOR ANTAGONISTS AND USES THEREOF
First Claim
Patent Images
1. A compound comprising a sequence characterized by the formula T1E2E3E4Q5Q6Y7L8, wherein said compound is 25 or fewer amino acids in length, wherein said compound antagonizes a biological activity of an interleukin 23 (IL-23) receptor, and wherein;
- T1 is selected from the group consisting of no residue, threonine, phenylalanine, alanine, and Σ
, where Σ
defines an alpha-amino acid comprising a hydrophobic side-chain Σ
or aromatic side chain;
E2, E3, and E4 each independently is selected from the group consisting of no residue, alanine, glutamic acid, glutamine, aspartic acid, asparagine, serine, histidine, homoserine, beta-leucine, beta-phenylalanine, alpha amino adipic acid, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine;
Q5 and Q6 each independently is selected from the group consisting of no residue, alanine, glutamine, aspartic acid, asparagine, glutamic acid, serine, homoserine, alpha-amino adipic acid, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine;
Y7 is selected from the group consisting of no residue, tyrosine, phenylalanine, tryptophan, alanine, histidine, pyridylalanine, and Σ
where Σ
is an alpha-amino acid comprising a hydrophobic side-chain Σ
or aromatic side chain or heteroaromatic side chain; and
L8 is selected from the group consisting of no residue, leucine, alanine, valine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine.
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Abstract
The present invention relates to IL-23 receptor antagonists and agonists. The use of IL-23 receptor antagonists in treating autoimmune and inflammatory disorders, as well as methods of identifying IL-23 receptor antagonists and agonists.
33 Citations
76 Claims
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1. A compound comprising a sequence characterized by the formula T1E2E3E4Q5Q6Y7L8, wherein said compound is 25 or fewer amino acids in length, wherein said compound antagonizes a biological activity of an interleukin 23 (IL-23) receptor, and wherein;
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T1 is selected from the group consisting of no residue, threonine, phenylalanine, alanine, and Σ
, where Σ
defines an alpha-amino acid comprising a hydrophobic side-chain Σ
or aromatic side chain;E2, E3, and E4 each independently is selected from the group consisting of no residue, alanine, glutamic acid, glutamine, aspartic acid, asparagine, serine, histidine, homoserine, beta-leucine, beta-phenylalanine, alpha amino adipic acid, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine;Q5 and Q6 each independently is selected from the group consisting of no residue, alanine, glutamine, aspartic acid, asparagine, glutamic acid, serine, homoserine, alpha-amino adipic acid, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine;Y7 is selected from the group consisting of no residue, tyrosine, phenylalanine, tryptophan, alanine, histidine, pyridylalanine, and Σ
where Σ
is an alpha-amino acid comprising a hydrophobic side-chain Σ
or aromatic side chain or heteroaromatic side chain; andL8 is selected from the group consisting of no residue, leucine, alanine, valine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine. - View Dependent Claims (2, 3, 4, 11, 12, 67, 70, 71, 75)
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5-10. -10. (canceled)
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13-17. -17. (canceled)
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18. A compound comprising a sequence characterized by the formula M1E2E3S4K5Q6L7Q8L9, wherein said compound is 25 or fewer amino acids in length, wherein said compound antagonizes a biological activity of an interleukin 23 (IL-23) receptor, and wherein;
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M1 is selected from the group consisting of no residue, methionine, valine, leucine, alanine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;E2 and E3 each independently is selected from the group consisting of no residue, alanine, glutamic acid, glutamine, aspartic acid, asparagine, serine, histidine, homoserine, beta-leucine, beta-phenylalanine, alpha amino adipic acid, trimesic acid, or an alpha,omega-dicarboxylic acid (e.g., succinic acid, glutaric acid, or azelic acid), and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine;S4 is selected from the group consisting of no residue, serine, threonine, allothreonine, hydroxyproline, beta-hydroxyvaline, valine, and η
, where η
is a neutral hydrophilic amino acid;K5 is selected from the group consisting of no residue, glutamine, lysine, arginine, histidine, alanine, ornithine, citruline, 2-pyridylalanine, 3-pyridylalanine, 4-pyridylalanine, and an arginine surrogate; Q6 is selected from the group consisting of no residue, alanine, glutamine, aspartic acid, asparagine, glutamic acid, serine, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine;L7 is selected from the group consisting of no residue, leucine, alanine, valine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine;Q8 is selected from the group consisting of no residue, glutamine, aspartic acid, asparagine, glutamic acid, serine, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine; andL9 is selected from the group consisting of no residue, leucine, isoleucine, alanine, valine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine. - View Dependent Claims (19, 27, 28)
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20-26. -26. (canceled)
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29-32. -32. (canceled)
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33. A compound comprising a sequence characterized by the formula K1K2Y3L4V5W6V7Q8, wherein said compound is 25 or fewer amino acid in length, wherein said compound antagonizes a biological activity of an interleukin 23 (IL-23) receptor, and wherein;
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K1 and K2 each independently is selected from the group consisting of no residue, lysine, arginine, histidine, alanine, ornithine, citruline, 2-pyridylalanine, 3-pyridylalanine, 4-pyridylalanine, and an arginine surrogate; Y3 is selected from the group consisting of no residue, tyrosine, phenylalanine, tryptophan, alanine, and Σ
where Σ
is an alpha-amino acid comprising a hydrophobic side-chain Σ
or aromatic side chain, or heteroaromatic side chain;L4 is selected from the group consisting of no residue, leucine, alanine, valine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine;V5 is selected from the group consisting of no residue, valine, leucine, alanine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine;W6 is selected from the group consisting of no residue, tryptophan, tyrosine, phenylalanine, alanine, and Σ
where Σ
is an alpha-amino acid comprising a hydrophobic side-chain Σ
or aromatic side chain;
or heteroaromatic side chain;V7 is selected from the group consisting of no residue, valine, leucine, alanine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine; andQ8 is selected from the group consisting of no residue, glutamine, aspartic acid, asparagine, glutamic acid, serine, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine. - View Dependent Claims (34)
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35-47. -47. (canceled)
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48. A compound comprising a sequence characterized by the formula L1P2D3E4V5T6C7V8, wherein said compound is 25 or fewer amino acids in length, wherein said compound antagonizes a biological activity of an interleukin 23 (IL-23) receptor, and wherein;
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L1 is selected from the group consisting of no residue, leucine, alanine, valine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;P2 is selected from the group consisting of no residue, proline, alanine, N-methylglycine, N-isobutylglycine, aminoisobutyric acid (Aib), N-Methyl-L-alanine (MeAla), trans-4-Hydroxyproline, diethylthiazolidine carboxylic acid (Dtc), and Ω
, where Ω
is a conformational constraint-producing amino acid;D3 is selected from the group consisting of no residue, aspartic acid, asparagine, glutamic acid, glutamine, serine, histidine, homoserine, beta-leucine, beta-phenylalanine, alpha amino adipic acid, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine, or a primary arylalkyl amine;E4 is selected from the group consisting of no residue, alanine, glutamic acid, glutamine, aspartic acid, asparagine, serine, histidine, homoserine, beta-leucine, beta-phenylalanine, alpha amino adipic acid, and Ψ
where Ψ
is a 3-amino-5-phenylpentanoic acid-alpha-amino acid comprising a hydrophobic side-chain, an aromatic amine, an aliphatic amine or a primary arylalkyl amine;V5 is selected from the group consisting of no residue, valine, leucine, alanine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine;
or a heteroaromatic or heteroarylalkylamine;T6 is selected from the group consisting of no residue, threonine, phenylalanine, alanine, and Σ
where Σ
defines an alpha-amino acid comprising a hydrophobic side-chain Σ
or aromatic side chain;C7 is selected from the group consisting of no residue, cysteine, serine, homoserine, homocysteine, threonine, methionine, N-acetylcysteine, cystathionine, 2-aminobutyrate, and β
,β
-dimethylcysteine (Penicillamine); andV8 is selected from the group consisting of no residue, valine, leucine, alanine, methionine, phenylalanine, tryptophan, and φ
where φ
is an alpha-amino acid comprising a hydrophobic side-chain;
an aliphatic amine of one to ten carbons;
or an aromatic or arylalkylamine. - View Dependent Claims (49)
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50-62. -62. (canceled)
- 63. A vector comprising an isolated nucleic acid sequence encoding the amino acid sequence of any one of SEQ ID NOS:
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65-66. -66. (canceled)
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68-69. -69. (canceled)
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72-74. -74. (canceled)
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76-79. -79. (canceled)
Specification