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US 10,329,340 B2Granted
Albumin variants
AssigneeAlbumedix Ltd
InventorKaren Ann Delahay
Life of this patent
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Abstract
The present invention relates to variants of a parent albumin, the variants having altered plasma half-life compared with the parent albumin. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.
Claims29
A method of producing a polypeptide comprising:
- providing a nucleic acid encoding an albumin having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 2 and having a substitution in Domain I of said albumin and having a substitution in Domain III of said albumin relative to the amino acid sequence set forth in SEQ ID NO:
- 2, wherein said albumin has an increased binding affinity to FcRn relative to the binding affinity of an albumin comprising the amino acid sequence of SEQ ID NO:
- 2 to FcRn, and wherein said substitution in Domain I is selected from amino acids corresponding to positions 82, 83, 111, 112, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2 and said substitution in Domain III is selected from amino acids corresponding to positions 425, 505, 510, 512, 524, 527, 531, 534, 569, 573, 575, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2;
- introducing the nucleic acid in a suitable host cell;
- and
- culturing the host cell under conditions that allow expression of the polypeptide.
6 more elements
A nucleic acid encoding a polypeptide comprising an albumin having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 2 and having a substitution in Domain I of said albumin and having a substitution in Domain III of said albumin relative to the amino acid sequence set forth in SEQ ID NO:
- 2, wherein said albumin has an increased binding affinity to FcRn relative to the binding affinity of an albumin comprising the amino acid sequence of SEQ ID NO:
- 2 to FcRn, and wherein said substitution in Domain I is selected from amino acids corresponding to positions 82, 83, 111, 112, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2 and said substitution in Domain III is selected from amino acids corresponding to positions 425, 505, 510, 512, 524, 527, 531, 534, 569, 573, 575, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2.
2 more elements
A method of producing a fusion polypeptide comprising:
- providing a nucleic acid encoding:
- (a) an albumin having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 2 and having a substitution in Domain I of said albumin and having a substitution in Domain III of said albumin relative to the amino acid sequence set forth in SEQ ID NO:
- 2, wherein said albumin has an increased binding affinity to FcRn relative to the binding affinity of an albumin comprising the amino acid sequence of SEQ ID NO:
- 2 to FcRn, and wherein said substitution in Domain I is selected from amino acids corresponding to positions 82, 83, 111, 112, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2 and said substitution in Domain III is selected from amino acids corresponding to positions 425, 505, 510, 512, 524, 527, 531, 534, 569, 573, 575, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2;
- and
- (b) a fusion partner polypeptide selected from a therapeutic, prophylactic, diagnostic, imaging or other moiety, wherein the fusion partner polypeptide is fused to the N-terminus of albumin, the C-terminus of albumin, or inserted into a loop in the albumin structure;
- introducing the nucleic acid in a suitable host cell;
- and
- culturing the host cell under conditions that allow expression of the polypeptide.
9 more elements
A nucleic acid encoding a fusion polypeptide comprising:
- an albumin having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 2 and having a substitution in Domain I of said albumin and having a substitution in Domain III of said albumin relative to the amino acid sequence set forth in SEQ ID NO:
- 2, wherein said albumin has an increased binding affinity to FcRn relative to the binding affinity of an albumin comprising the amino acid sequence of SEQ ID NO:
- 2 to FcRn, and wherein said substitution in Domain I is selected from amino acids corresponding to positions 82, 83, 111, 112, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2 and said substitution in Domain III is selected from amino acids corresponding to positions 425, 505, 510, 512, 524, 527, 531, 534, 569, 573, 575, or any combination thereof of the amino acid sequence of SEQ ID NO:
- 2;
- and
- a fusion partner polypeptide selected from a therapeutic, prophylactic, diagnostic, imaging or other moiety.
5 more elements
Dependencies are inferred from the claim text.