Melanoma antigen peptide analogues
AssigneeMannKind Corporation
InventorsLiping Liu, Adrian Bot, David C. Diamond
Life of this patent
Estimating the term…
Abstract
Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally, classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.
Claims23
An isolated peptide analogue of an immunogenic peptide expressed by a pSEM plasmid consisting essentially of the sequence:
- E{A, L, Nva, Nle}AGIGILT{V,
- (SEQ ID NO:91)
- Nva, Nle};
- or
- Y{M, V, Nva, Nle}DGTMSQ{V, Nva,
- (SEQ ID NO:92)
- Nle};
- and wherein the sequence is not E{A, L}AGIGILTV (SEQ ID NO:
- 93) or YMDGTMSQV (SEQ ID NO:
- 94).
An isolated peptide analogue comprising a substitution in at least one position, wherein the at least one position is at amino acid position 2 or 10, in the sequence EAAGIGILTV (SEQ ID NO:
- 100) having an affinity for a class I MHC binding cleft that is similar to or greater than the affinity of EAAGIGILTV (SEQ ID NO:
- 100) for said class I MHC binding cleft.
An isolated peptide analogue comprising a substitution in at least one position, wherein the at least one position is at amino acid position 2 or 9, in the sequence YMDGTMSQV (SEQ ID NO:
- 94) having an affinity for a class I MHC binding cleft that is similar to or greater than the affinity of YMDGTMSOV (SEQ ID NO:
- 94) for said class I MHC binding cleft.
An isolated peptide analogue of an immunogenic peptide expressed by a pSEM plasmid consisting of the following:
- (a) E{A, L, Nva, Nle}AGIGILT{V, Nva, Nle} (SEQ ID NO:
- 91), wherein the sequence is not E{A, L}AGIGILTV (SEQ ID NO:
- 93);
- or
- (b) Y{M, V, Nva, Nle}DGTMSQ{V, Nva, Nle} (SEQ ID NO:
- 92), wherein the sequence is not YMDGTMSQV (SEQ ID NO:
- 94);
- or
- (c) either of (a) or (b) further consisting of an N-terminal extension, a C-terminal extension, or both.
An isolated peptide analogue of an immunogenic peptide expressed by a pSEM plasmid comprising the sequence:
- E{A, L, Nva, Nle}AGJGILT{V, Nva, Nle} (SEQ ID NO:
- 91);
- or
- Y{M, V, Nva, Nle}DGTMSQ{V, Nva, Nle} (SEQ ID NO:
- 92);
- and wherein the sequence is not E{A, L}AGIGILTV (SEQ ID NO:
- 93) or YMDGTMSQV (SEQ ID NO:
- 94).
An isolated peptide consisting of the sequence P0-P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11, in which:
- P0 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid;
- and
- P1 is E;
- and
- P2 is A, L, Nva, or Nle;
- and
- P3 is A;
- and
- P4 is G;
- and
- P5 is I;
- and
- P6 is G;
- and
- P7 is I;
- and
- P8 is L;
- and
- P9 is T;
- and
- [[PΩat ]]P10 is V, Nva, or Nle;
- and
- [[PΩ+1]]P11 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid;
- and
- wherein the sequence does not comprise E{A, L}AGIGILTV (SEQ ID NO:
- 93).
An isolated peptide consisting of the sequence P0-P1-P2-P3-P4-P5-P6-P7-P8-P9-P10, in which:
- P0 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid;
- and
- P1 is Y;
- and
- P2 is M, V, Nva, or Nie;
- and
- P3 is D;
- and
- P4 is G;
- and
- P5 is T;
- and
- P6 is M;
- and
- P7 is 5;
- and
- P8 is Q;
- and
- [[PΩat P9]]is V, Nva, or Nle;
- and
- [[PΩ+1]]P10 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid;
- and
- and wherein the sequence does not comprise YMDGTMSQV (SEQ ID NO:
- 94).
Dependencies are inferred from the claim text.