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US 2002/0176866 A1Published application
Methods for treatment of multiple sclerosis using peptide analogs of human myelin basic protein
AssigneeNeurocrine Biosciences, Inc.
InventorsAmitabh Gaur, Paul Conlon, Nicholas C. Ling, Theophil Staehelin, Paul D. Crowe
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Abstract
The present invention is directed toward peptide analogs of human myelin basic protein. The peptide analog is at least seven amino acids long and derived from residues 83 to 99 of human myelin basic protein. The analogs are altered from the native sequence at least at positions 91, 95, or 97. Additional alterations may be made at other positions Pharmaceutical compositions containing these peptide analogs are provided. The peptide analogs are useful for treating multiple sclerosis.
Claims67
A method for inducing a Th2 immune response to myelin basic protein or a peptide analog thereof in a patient, comprising:
- administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising a peptide analog selected from the group consisting of:
- (a) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 91, wherein the L-lysine at position 91 is altered to another amino acid, and one to three L-amino acids selected from the group consisting of valine at position 86, valine at position 87, histidine at position 88, threonine at position 95, threonine at position 98 and proline at position 99 are altered to an amino acid other than the amino acid present in the native protein at that position;
- (b) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 97, wherein the L-arginine at position 97 is altered to another amino acid and one to three L-amino acids selected from the group consisting of valine at position 86, valine at position 87, histidine at position 88, threonine at position 95, threonine at position 98 and proline at position 99 are altered to an amino acid other than the amino acid present in the native protein at that position;
- (c) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 95, wherein the L-threonine at position 95 is altered to another amino acid and one to three L-amino acids selected from the group consisting of valine at position 86, valine at position 87, histidine at position 88, threonine at position 98 and proline at position 99 are altered to an amino acid other than the amino acid present in the native protein at that position;
- (d) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 91, wherein the L-lysine at position 91 is altered to another amino acid and the N-terminal amino acid and/or the C-terminal amino acid are altered to another amino acid, such that upon administration of the peptide analog in vivo proteolysis is reduced;
- (e) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 95, wherein the L-lysine at position 91 is altered to another amino acid and the N-terminal amino acid and/or the C-terminal amino acid are altered to another amino acid, such that upon administration of the peptide analog in vivo proteolysis is reduced;
- (f) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 97, wherein the L-lysine at position 91 is altered to another amino acid and the N-terminal amino acid and/or the C-terminal amino acid are altered to another amino acid, such that upon administration of the peptide analog in vivo proteolysis is reduced;
- (g) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 91, wherein the L-lysine at position 91 is altered to another amino acid;
- (h) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 95, wherein the L-threonine at position 95 is altered to another amino acid;
- and
- (i) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 97, wherein the L-arginine at position 97 is altered to another amino acid;
- wherein the peptide analog is administered in combination with a physiologically acceptable carrier/adjuvant or diluent.
9 more elements
A method for inducing a Th2 immune response to myelin basic protein or a peptide analog thereof in a patient, comprising:
- administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising a peptide analog, wherein the peptide analog comprises at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 91, wherein the L-lysine at position 91 is altered to another amino acid, and two to four additional L-amino acids selected from residues 83 to 90 and 92 to 99 are altered to an amino acid other than the amino acid present in the native protein at that position,
- wherein the peptide analog is administered in combination with a physiologically acceptable carrier or diluent.
A method for inducing a Th2 immune response to myelin basic protein or a peptide analog thereof in a patient, comprising:
- administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising a peptide analog comprising the sequence D-Ala-Lys-Pro-Val-Val-His-Leu-Phe-Ala-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro (SEQ ID NO:
- 7).
A method for inducing a persistent systemic immune response to myelin basic protein or a peptide analog thereof in a patient, comprising:
- administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising a peptide analog selected from the group consisting of
- (a) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 91, wherein the L-lysine at position 91 is altered to another amino acid, and one to three L-amino acids selected from the group consisting of valine at position 86, valine at position 87, histidine at position 88, threonine at position 95, threonine at position 98 and proline at position 99 are altered to an amino acid other than the amino acid present in the native protein at that position;
- (b) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 97, wherein the L-arginine at position 97 is altered to another amino acid and one to three L-amino acids selected from the group consisting of valine at position 86, valine at position 87, histidine at position 88, threonine at position 95, threonine at position 98 and proline at position 99 are altered to an amino acid other than the amino acid present in the native protein at that position;
- (c) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 95, wherein the L-threonine at position 95 is altered to another amino acid and one to three L-amino acids selected from the group consisting of valine at position 86, valine at position 87, histidine at position 88, threonine at position 98 and proline at position 99 are altered to an amino acid other than the amino acid present in the native protein at that position;
- (d) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 91, wherein the L-lysine at position 91 is altered to another amino acid and the N-terminal amino acid and/or the C-terminal amino acid are altered to another amino acid, such that upon administration of the peptide analog in vivo proteolysis is reduced;
- (e) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 95, wherein the L-lysine at position 91 is altered to another amino acid and the N-terminal amino acid and/or the C-terminal amino acid are altered to another amino acid, such that upon administration of the peptide analog in vivo proteolysis is reduced;
- (f) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 97, wherein the L-lysine at position 91 is altered to another amino acid and the N-terminal amino acid and/or the C-terminal amino acid are altered to another amino acid, such that upon administration of the peptide analog in vivo proteolysis is reduced;
- (g) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 91, wherein the L-lysine at position 91 is altered to another amino acid;
- (h) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 95, wherein the L-threonine at position 95 is altered to another amino acid;
- and
- (i) peptide analogs comprising at least seven amino acids selected from residues 83 to 99 of human myelin basic protein, including residue 97, wherein the L-arginine at position 97 is altered to another amino acid;
- wherein the peptide analog is administered in combination with a physiologically acceptable carrier or diluent.
9 more elements
Dependencies are inferred from the claim text.