US2003191065A1PendingUtilityA1
Modified proinsulin variants and composition containing same
Priority: Jan 6, 1999Filed: May 22, 2003Published: Oct 9, 2003
Est. expiryJan 6, 2019(expired)· nominal 20-yr term from priority
A61P 37/04A61P 9/10A61P 5/02A61P 3/10A61P 9/04A61P 5/50A61P 41/00A61P 5/44A61P 3/08A61P 5/38A61P 5/48A61P 9/00A61P 43/00A61P 37/00A61P 31/18A61P 25/28A61P 25/24A61P 25/00A61P 25/18A61P 3/04A61P 35/00A61P 25/02A61K 38/00A61P 11/00A61P 1/14A61P 19/10C07K 14/65A61P 11/16A61P 15/00A61P 21/00A61P 19/00A61P 13/12A61P 17/02A61P 15/08A61P 19/04A61P 21/04A61P 17/00
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Claims
Abstract
IGF-I and insulin variants are provided that selectively bind to IGFBP- 1 or IGFBP- 3. These agonist variants are useful, for example, to improve the half-lives of IGF-I and insulin, respectively.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . An IGF-I variant wherein an amino acid at position 3,4, 5, 7, 10, 14, 17, 23, 24, 25, 43, 49 or 63, or any of such amino acids in combination with an amino acid at position 12 or 16 or both 12 and 16 of native-sequence human IGF-I, or any combination thereof, is replaced with any amino acid at said position 7 or with an alanine, a glycine, or a serine residue at any position other than said position 7.
2 . The variant of claim 1 wherein an amino acid at said position 3 is replaced.
3 . The variant of claim 1 wherein an amino acid at said position 4 is replaced.
4 . The variant of claim 1 wherein an amino acid at said position 5 is replaced.
5 . The variant of claim 1 wherein an amino acid at said position 7 is replaced.
6 . The variant of claim 1 wherein an amino acid at said position 10 is replaced.
7 . The variant of claim 1 wherein an amino acid at said position 14 is replaced.
8 . The variant of claim 1 wherein an amino acid at said position 17 is replaced.
9 . The variant of claim 1 wherein an amino acid at said position 23 is replaced.
10 . The variant of claim 1 wherein an amino acid at said position 24 is replaced.
11 . The variant of claim 1 wherein an amino acid at said position 25 is replaced.
12 . The variant of claim 1 wherein an amino acid at said position 43 is replaced.
13 . The variant of claim 1 wherein an amino acid at said position 49 is replaced.
14 . The variant of claim 1 wherein an amino acid at said position 63 is replaced.
15 . The variant of claim 1 wherein amino acids at said positions 16 and 49 are replaced.
16 . The variant of claim 1 wherein amino acids at said positions 3 and 7 are replaced.
17 . The variant of claim 15 wherein additionally tyrosine at said position 24 is replaced with leucine or tyrosine at said position 31 is replaced with alanine or both are replaced.
18 . The variant of claim 16 wherein additionally tyrosine at said position 24 is replaced with leucine or tyrosine at said position 31 is replaced with alanine or both are replaced.
19 . The variant of claim 17 wherein both tyrosines are replaced.
20 . The variant of claim 18 wherein both tyrosines are replaced.
21 . An IGF-I variant wherein an amino acid at position 3, 4, 5, 7, 10, 14, 17, 23, 24, 25, or 43, or any combination thereof, of native-sequence human IGF-I is replaced with any amino acid at said position 7 or with an alanine, a glycine, or a serine residue at any position other than said position 7.
22 . An IGF-I variant wherein an amino acid at position 3, 4, 5, 7, 10, 14, 17, 23, 24, 25,43, or 49, or any combination thereof, of native-sequence human IGF-I is replaced with any amino acid at said position 7 or with an alanine, a glycine, or a serine residue at any position other than said position 7.
23 . An IGF-I variant wherein an amino acid at position 3, 4, 5, 7, 10, 14, 17,23, 24,25, 43, or 63, or any combination thereof, of native-sequence human IGF-I is replaced with any amino acid at said position 7 or with an alanine, a glycine, or a serine residue at any position other than said position 7.
24 . IGF-like insulin wherein phenylalanine at position 1 of native-sequence human pro-insulin is deleted, or glutamine at position 4 of native-sequence human pro-insulin is replaced with glutamic acid, or leucine at position 17 of native-sequence human pro-insulin is replaced with phenylalanine, or phenylalanine at position 25 of native-sequence human pro-insulin is replaced with tyrosine, or tyrosine at position 26 of native-sequence human pro-insulin is replaced with phenylalanine, or threonine at position 73 of native-sequence human pro-insulin is replaced with phenylalanine, or any combination thereof.
25 . The insulin of claim 24 wherein the amino acid at position 1 is deleted and the amino acid at said position 25 is replaced.
26 . The insulin of claim 24 wherein the amino acid at position 1 is deleted andthe amino acid at said position 26 is replaced.
27 . The insulin of claim 24 wherein the amino acid at position 1 is deleted and the amino acid at said position 73 is replaced.
28 . The insulin of claim 24 wherein the amino acid at position 1 is deleted and the amino acids at said positions 25 and 26 are replaced.
29 . The insulin of claim 24 wherein the amino acid at position 1 is deleted and the amino acids at said positions 25 and 73 are replaced.
30 . The insulin of claim 24 wherein the amino acid at position 1 is deleted and the amino acids at said positions 26 and 73 are replaced.
31 . The insulin of claim 24 wherein the amino acid at position 1 is deleted and the amino acids at said positions 25, 26, and 73 are replaced.
32 . The insulin of claim 24 wherein amino acids at said positions 4 and 17 are replaced.
33 . The insulin of claim 24 wherein amino acids at said positions 4 and 26 are replaced.
34 . The insulin of claim 24 wherein amino acids at said positions 4 and 73 are replaced.
35 . The insulin of claim 24 wherein amino acids at said positions 17 and 26 are replaced.
36 . The insulin of claim 24 wherein amino acids at said positions 17 and 73 are replaced.
37 . The insulin of claim 24 wherein amino acids at said positions 26 and 73 are replaced.
38 . The insulin of claim 24 wherein amino acids at said positions 4, 17, and 26 are replaced.
39 . The insulin of claim 24 wherein amino acids at said positions 4, 17, and 73 are replaced.
40 . The insulin of claim 24 wherein amino acids at said positions 4, 26, and 73 are replaced.
41 . The insulin of claim 24 wherein amino acids at said positions 17, 26, and 73 are replaced.
42 . IGF-like insulin wherein phenylalanine at position 1 of native-sequence human pro-insulin is deleted, or glutamine at position 4 of native-sequence human pro-insulin is replaced with glutamic acid, or phenylalanine at position 25 of native-sequence human pro-insulin is replaced with tyrosine, or tyrosine at position 26 of native-sequence human pro-insulin is replaced with phenylalanine, or threonine at position 73 of native-sequence human pro-insulin is replaced with phenylalanine, or any combination thereof.
43 . IGF-like insulin wherein the phenylalanine at position 1 is deleted, or glutamine at position 4 ofnative-sequence human mature insulin is replaced with glutamic acid, or leucine at position 17 of native-sequence human mature insulin is replaced with phenylalanine, or phenylalanine at position 25 of native-sequence human mature insulin is replaced with tyrosine, or tyrosine at position 26 of native-sequence human mature insulin is replaced with phenylalanine, or threonine at position 38 of native-sequence human mature insulin is replaced with phenylalanine, or any combination thereof.
44 . The insulin of claim 43 wherein amino acids at said positions 4, 17, 26, and 38 are replaced.
45 . The insulin of claim 43 wherein the amino acid at position 1 is deleted and amino acids at said positions 25, 26, and 38 are replaced.
46 . IGF-like insulin wherein the phenylalanine at position 1 is deleted, or glutamine at position 4 of native-sequence human mature insulin is replaced with glutamic acid, or phenylalanine at position 25 of native-sequence human mature insulin is replaced with tyrosine, or tyrosine at position 26 of native-sequence human mature insulin is replaced with phenylalanine, or threonine at position 38 of native-sequence human mature insulin is replaced with phenylalanine, or any combination thereof.
47 . A composition comprising the variant of claim 1 in a carrier.
48 . A composition comprising the insulin of claim 24 in a carrier.
49 . A composition comprising the insulin of claim 43 in a carrier.Join the waitlist — get patent alerts
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