Muteins of hypoxia inducible factor alpha and methods of use thereof
First Claim
1. A hypoxia inducible factor (HIF) mutein polypeptide wherein one or more of a hydroxylatable amino acid residue in a wild type HIFα
- polypeptide are mutated, said HIF mutein displaying decreased binding to VHL, increased resistance to degradation in the presence of oxygen and comprises both functional wild type HIFα
polypeptide transactivation domains.
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Accused Products
Abstract
The present invention provides hypoxia inducible factor alpha muteins, DNA sequences encoding these hypoxia inducible factor alpha muteins, recombinant DNA molecules containing those DNA sequences operatively linked to expression control sequences and capable of inducing expression of an hypoxia inducible factor alpha muteins, hosts transformed with those recombinant DNA molecules, pharmaceutical compositions containing hypoxia inducible factor alpha muteins and methods of using those compositions to treat hypoxia and ischemic related tissue damage.
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Citations
22 Claims
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1. A hypoxia inducible factor (HIF) mutein polypeptide wherein one or more of a hydroxylatable amino acid residue in a wild type HIFα
- polypeptide are mutated, said HIF mutein displaying decreased binding to VHL, increased resistance to degradation in the presence of oxygen and comprises both functional wild type HIFα
polypeptide transactivation domains. - View Dependent Claims (2, 3, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22)
- polypeptide are mutated, said HIF mutein displaying decreased binding to VHL, increased resistance to degradation in the presence of oxygen and comprises both functional wild type HIFα
-
4. A hypoxia inducible factor (HIF) mutein polypeptide wherein the amino acid at position 564 in wild type HIFα
- , numbered in accordance with wild type HIFα
is not a proline, said HIF mutein displaying decreased binding to VHL and increased resistance to degradation in the presence of oxygen. - View Dependent Claims (8, 9)
- , numbered in accordance with wild type HIFα
-
5. A hypoxia inducible factor (HIF) mutein polypeptide comprising the amino acid sequence at least 85% similar to wild type HIFα
- , wherein the amino acid at position 564 in wild type HIFα
, numbered in accordance with wild type HIFα
is not a proline, said HIF mutein displaying decreased binding to VHL and increased resistance to degradation in the presence of oxygen.
- , wherein the amino acid at position 564 in wild type HIFα
-
6. A hypoxia inducible factor (HIF) mutein polypeptide wherein the amino acid at position 562 in wild type HIFα
- , numbered in accordance with wild type HIFα
is not a leucine, said HIF mutein displaying decreased binding to VHL and increased resistance to degradation in the presence of oxygen. - View Dependent Claims (10)
- , numbered in accordance with wild type HIFα
-
7. A hypoxia inducible factor (HIF) mutein polypeptide comprising the amino acid sequence at least 85% similar to wild type HIFα
- , wherein the amino acid at position 562 in wild type HIFα
, numbered in accordance with wild type HIFα
is not a leucine, said HIF mutein displaying decreased binding to VHL and increased resistance to degradation in the presence of oxygen.
- , wherein the amino acid at position 562 in wild type HIFα
-
11. A HIF mutein polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2 or SEQ ID NO;
4.
- 2 or SEQ ID NO;
-
13. The nucleic acid comprising the nucleotide sequence of SEQ ID NO:
- 1 or SEQ ID NO;
3).
- 1 or SEQ ID NO;
Specification