Toxin peptide therapeutic agents
First Claim
1. A DNA encoding a composition of matter for extending the half-life of a polypeptide, of the formula
(X1)a—
- (F1)d—
(X2)b—
(F2)e—
(X3)c or multimers thereof, wherein;
F1 and F2 are half-life extending moieties selected from;
(i) a human IgG Fc domain or a portion thereof,(ii) a transthyretin protein domain, and(iii) a human serum albumin (HSA) protein domain;
and d and e are each independently 0 or 1, provided that at least one of d and e is 1;
X1, X2, and X3 are each independently -(L)f-P-(L)g-, and f and g are each independently 0 or 1;
P is a polypeptide of no more than about 80 amino acid residues in length, comprising the amino acid sequence of SEQ ID NO;
914, SEQ ID NO;
915, SEQ ID NO;
916, or SEQ ID NO;
917;
L is a linker; and
a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1.
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Accused Products
Abstract
Disclosed is a DNA encoding a composition of matter of the formula
(X1)a—(F1)d—(X2)b—(F2)e—(X3)c (I)
and multimers thereof, in which F1 and F2 are half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X1, X2, and X3 are each independently -(L)f-P-(L)g-, and f and g are each independently 0 or 1; P is a ShK peptide analog of no more than about 80 amino acid residues in length; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. A DNA encoding the ShK peptide analog is disclosed. Also disclosed are an expression vector comprising the DNA, and a host cell comprising the expression vector.
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Citations
24 Claims
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1. A DNA encoding a composition of matter for extending the half-life of a polypeptide, of the formula
(X1)a—- (F1)d—
(X2)b—
(F2)e—
(X3)cor multimers thereof, wherein; F1 and F2 are half-life extending moieties selected from; (i) a human IgG Fc domain or a portion thereof, (ii) a transthyretin protein domain, and (iii) a human serum albumin (HSA) protein domain; and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X1, X2, and X3 are each independently -(L)f-P-(L)g-, and f and g are each independently 0 or 1; P is a polypeptide of no more than about 80 amino acid residues in length, comprising the amino acid sequence of SEQ ID NO;
914, SEQ ID NO;
915, SEQ ID NO;
916, or SEQ ID NO;
917;L is a linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 19, 20, 21, 22, 23, 24)
P-(L)g-F1—
F2, and
P-(L)g-F1—
F2-(L)f-P.
- (F1)d—
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3. The DNA of claim 1, wherein F1 or F2, or both, comprises a human IgG Fc domain or a portion thereof.
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4. The DNA of claim 3, wherein the human IgG Fc domain comprises a human IgG1 Fc domain.
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5. The DNA of claim 4, wherein the human IgG Fc domain comprises a human IgG2 Fc domain.
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6. The DNA of claim 1, wherein F1 and F2 are different half-life extending moieties.
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7. The DNA of claim 1, wherein claim 1, wherein any f or any g is 1, and L is a peptide linker comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 79, 84, and 637 through 656.
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8. The DNA of claim 1, wherein F1 or F2, or both, comprises a human serum albumin protein domain or a transthyretin protein domain.
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9. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:
- 914.
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10. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:
- 915.
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11. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:
- 916.
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12. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:
- 917.
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18. An expression vector comprising the DNA of claim 1 or claim 13.
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19. A host cell comprising the expression vector of claim 18.
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20. The host cell of claim 19, wherein the cell is a eukaryotic cell.
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21. The host cell of claim 20, wherein the cell is a mammalian cell.
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22. The host cell of claim 21, wherein the cell is a CHO cell.
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23. The host cell of claim 19, wherein the cell is a prokaryotic cell.
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24. The host cell of claim 23, wherein the cell is an E. coli cell.
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13. A DNA encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 914, SEQ ID NO;
915, SEQ ID NO;
916, or SEQ ID NO;
917. - View Dependent Claims (14, 15, 16, 17)
- 914, SEQ ID NO;
Specification