Cysteine-optimized stradomers
AssigneeGliknik Inc.
InventorsHenrik OLSEN, David S. BLOCK
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Abstract
The present disclosure involves biologically active proteins termed cysteine-optimized multimerizing stradomers. Thus, the present disclosure provides compositions and methods providing anti-autoimmune and anti-inflammatory activities, useful in the treatment of diseases and conditions including autoimmune diseases, inflammatory diseases, or infectious diseases.
Claims57
A cysteine-optimized multimerizing stradomer unit comprising (i) at least one IgG Fc domain;
- and (ii) at least one multimerization domain,
- wherein the stradomer unit comprises at least two stradomer unit monomers and wherein at least one of the at least two stradomer unit monomers comprises at least one point mutation at a cysteine residue in the IgG Fc domain monomer or the multimerization domain monomer of the at least one stradomer unit monomer.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims, wherein the at least one point mutation is mutated from cysteine to a serine.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims wherein the number of cysteines present in the amino acid sequence of the stradomer is 10.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims wherein the number of cysteines present in the amino acid sequence of the stradomer is 9.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims, wherein the number of cysteines present in the amino acid sequence of the stradomer is 8.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims wherein the number of cysteines present in the amino acid sequence of the stradomer is 7 or fewer.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims, wherein one or both of the at least two stradomer unit monomers comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 27, 30, 35, 36, 40, 41, and 42.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims, wherein the cysteine-optimized multimerizing stradomer unit exhibits increased multimerization relative to a stradomer comprising SEQ ID NO:
- 10.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims wherein the stradomer unit exhibits the same multimerization relative to a stradomer comprising SEQ ID NO:
- 10.
The cysteine-optimized multimerizing stradomer unit of any one of the previous claims wherein the stradomer exhibits decreased multimerization relative to a stradomer unit comprising SEQ ID NO:
- 10.
A method of treating or preventing an inflammatory, autoimmune, or infectious disease or disorder, the method comprising administering a pharmaceutical formulation comprising a cysteine optimized stradomer comprised of two or more the cysteine-optimized stradomer units of any one of the previous claims.
A cysteine-optimized multimerizing stradomer unit comprising, (i) at least one IgG1 Fc domain comprising an IgG1 hinge, IgG1 CH2, and IgG1 CH3;
- and (ii) at least one IgG2 hinge,
- wherein the stradomer unit comprises at least two stradomer unit monomers and wherein at least one of the at least two stradomer unit monomers comprises at least one point mutation at a cysteine residue in the IgG1 Fc domain monomer or the IgG2 hinge domain monomer of the at least one stradomer unit monomer.
Dependencies are inferred from the claim text.