Modified interferon-gamma polypeptides and methods for using modified interferon-gamma polypeptides
First Claim
Patent Images
1. A modified interferon-γ
- polypeptide, comprising one or more amino acid replacements in an unmodified IFN-γ
polypeptide at positions corresponding to any of amino acid positions 2, 5-12, 14-18, 24, 27-29, 31, 32, 35, 36, 39, 44, 45, 48, 51, 53-55, 57, 59, 60, 62, 63, 71-80, 83, 84, 89-99, 100, 101, 105, 106, 109, 115, 117, 122, 123, 125, 128, 131-134, 137-139, 142, 143 of a mature interferon-γ
, wherein;
the mature human interferon-γ
comprises the sequence of amino acids set forth in SEQ ID NO;
1;
the modified interferon-γ
polypeptide exhibits increased protein stability compared to the unmodified human interferon-γ
; and
if position 5 is replaced, the replacing amino acid is not cysteine;
if position 6, 12, 17, 24, 62, 71, 74, 75, 77, 78, 89, 93, 96, 105, or 106 is replaced, the replacing amino acid is not cysteine;
if position 9 or 28 is replaced, the replacing amino acid is not glutamine or cysteine;
if position 15, 83 or 90 is replaced, the replacing amino acid is not serine, cysteine, or threonine;
if position 29 is replaced, the replacing amino acid is not phenylalanine, asparagine, tyrosine, glutamine, valine, alanine, methionine, isoleucine, lysine, arginine, threonine, histidine, cysteine, or serine;
if position 31 is replaced, the replacing amino acid is not histidine, aspartic acid, alanine, methionine, asparagine, threonine, arginine, serine, or cysteine;
if position 18, 32, 55, 57, 60, 63, 84, 95, or 139 is replaced, the replacing amino acid is not valine;
if position 48, 73, or 143 is replaced, the replacing amino acid is not asparagine;
if position 97 or 122 is replaced, the replacing amino acid is not asparagine or cysteine;
if position 100 is replaced, the replacing amino acid is not glutamine;
if position 101 is replaced, the replacing amino acid is not phenylalanine, asparagine, glutamine, valine, alanine, methionine, isoleucine, lysine, glycine, arginine, threonine, histidine, cysteine, or serine;
if position 109 is replaced, the replacing amino acid is not serine or threonine; and
if position 133 is replaced, the replacing amino acid is not asparagine.
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Abstract
Provided are modified interferon-gamma (IFN-γ) polypeptides and methods of generating modified interferon-gamma polypeptides. Also provided are methods of treatment using modified interferon-gamma polypeptides.
78 Citations
67 Claims
-
1. A modified interferon-γ
- polypeptide, comprising one or more amino acid replacements in an unmodified IFN-γ
polypeptide at positions corresponding to any of amino acid positions 2, 5-12, 14-18, 24, 27-29, 31, 32, 35, 36, 39, 44, 45, 48, 51, 53-55, 57, 59, 60, 62, 63, 71-80, 83, 84, 89-99, 100, 101, 105, 106, 109, 115, 117, 122, 123, 125, 128, 131-134, 137-139, 142, 143 of a mature interferon-γ
, wherein;
the mature human interferon-γ
comprises the sequence of amino acids set forth in SEQ ID NO;
1;
the modified interferon-γ
polypeptide exhibits increased protein stability compared to the unmodified human interferon-γ
; and
if position 5 is replaced, the replacing amino acid is not cysteine;
if position 6, 12, 17, 24, 62, 71, 74, 75, 77, 78, 89, 93, 96, 105, or 106 is replaced, the replacing amino acid is not cysteine;
if position 9 or 28 is replaced, the replacing amino acid is not glutamine or cysteine;
if position 15, 83 or 90 is replaced, the replacing amino acid is not serine, cysteine, or threonine;
if position 29 is replaced, the replacing amino acid is not phenylalanine, asparagine, tyrosine, glutamine, valine, alanine, methionine, isoleucine, lysine, arginine, threonine, histidine, cysteine, or serine;
if position 31 is replaced, the replacing amino acid is not histidine, aspartic acid, alanine, methionine, asparagine, threonine, arginine, serine, or cysteine;
if position 18, 32, 55, 57, 60, 63, 84, 95, or 139 is replaced, the replacing amino acid is not valine;
if position 48, 73, or 143 is replaced, the replacing amino acid is not asparagine;
if position 97 or 122 is replaced, the replacing amino acid is not asparagine or cysteine;
if position 100 is replaced, the replacing amino acid is not glutamine;
if position 101 is replaced, the replacing amino acid is not phenylalanine, asparagine, glutamine, valine, alanine, methionine, isoleucine, lysine, glycine, arginine, threonine, histidine, cysteine, or serine;
if position 109 is replaced, the replacing amino acid is not serine or threonine; and
if position 133 is replaced, the replacing amino acid is not asparagine. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 18, 19, 20, 21, 23, 25, 26, 28, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67)
- polypeptide, comprising one or more amino acid replacements in an unmodified IFN-γ
-
15. A modified human interferon-γ
- polypeptide, comprising two or more amino acid replacements in an unmodified IFN-γ
polypeptide at positions corresponding to any of amino acid positions of a mature interferon-γ
polypeptide, wherein;
the mature human interferon-γ
comprises the sequence of amino acids set forth in SEQ ID NO;
1; and
the modified interferon-γ
exhibits increased protein stability compared to the unmodified interferon-γ
polypeptide. - View Dependent Claims (16, 22, 24, 27, 29, 35)
- polypeptide, comprising two or more amino acid replacements in an unmodified IFN-γ
-
47. A modified interferon-γ
- , comprising any of the sequences of amino acids set forth in SEQ ID NOS;
3-11, 13-27, 29-32, 34-37, 41, 42, 45, 46, 55-59, 63-65, 69, 77-91, 93-105, 107-109, 111-113, 116-124, 126-135, 137-144, 146-217, 219-239, 241-350, 354-361, 368 and 369, or an active portion thereof.
- , comprising any of the sequences of amino acids set forth in SEQ ID NOS;
Specification