Modified proinsulin variants and composition containing same
OwnerYves Dubaquie, Henry Lowmaninventors
Life of this patent
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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.
Claims49
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.
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.
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.
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.
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.
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.
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.
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.
Dependencies are inferred from the claim text.