Stabilized fibronectin based scaffold molecules
AssigneeBristol-Myers Squibb Company
InventorDasa LIPOVSEK
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Abstract
Provided herein are proteins comprising a fibronectin based scaffold (FBS) domain, e.g., 10Fn3 molecules, that bind specifically to a target, and wherein the FBS domain is linked at its C-terminus to a region consisting of PmXn, wherein P is proline, X is any amino acid and wherein n is 0 or an integer that is at least 1 and m is an integer that is at least 1, and wherein the PmXn moiety provides an enhanced property to the FBS domain, e.g., enhanced stability, relative to the protein that is not linked to the PmXn moiety.
Claims29
1-17. (canceled)
A nucleic acid encoding a multivalent fibronectin based scaffold (FBS) protein comprising two or more 10Fn3 domains, wherein each of the 10Fn3 domains comprises an amino acid sequence that is at least 70% identical to SEQ ID NO:
- 1, and wherein (i) the C-terminal amino acid at the position corresponding to position 94 of SEQ ID NO:
- 1 of at least one 10Fn3 domain is covalently linked through a peptide bond to a moiety consisting of the amino acid sequence PmXn, wherein P is proline, X is any amino acid, m is an integer that is at least 1 and n is 0 or an integer that is at least 1;
- and
- (ii) the PmXn moiety provides an enhanced property to the multivalent FBS protein relative to the FBS protein that is not linked to the PmXn moiety.
An isolated FBS protein that specifically binds to a target, wherein the FBS is a non-naturally occurring FBS, and wherein the FBS is linked at its C-terminus to a moiety consisting of the amino acid sequence PmXn, wherein P is proline, X is any amino acid, m is an integer that is at least 1 and n is 0 or an integer that is at least 1, and wherein the PmXn moiety provides an enhanced property to the FBS protein relative to the FBS protein that is not linked to the PmXn moiety.
A method of producing an FBS protein drug conjugate, the method comprising covalently linking a drug moiety to an FBS protein,
- wherein the FBS is linked at its C-terminus to a moiety consisting of the amino acid sequence PmXn, wherein P is proline, X is any amino acid, m is an integer that is at least 1 and n is 0 or an integer that is at least 1, and wherein the PmXn moiety provides an enhanced property to the FBS protein relative to the FBS protein that is not linked to the PmXn moiety, and
- wherein the drug moiety is linked to the PmXn moiety of the FBS protein.
Dependencies are inferred from the claim text.