Antigen binding constructs to target molecules
AssigneeImaginab, Inc.
InventorsChio Mui Chan, Jean Marie Gudas, Tove Olafsen, Daulet Kadyl Satpayev, Michael Yuri Torgov
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Abstract
Antigen binding constructs that bind to desired targets are disclosed, for example antibodies, including antibody fragments (such as scFv and minibodies) that bind to a target molecule, and have one or more of the disclosed hinges are described herein. Methods of use are described herein.
Claims85
An amino acid hinge region comprising a sequence of SEQ ID NO:
- 1 (Xn1CXn2Xn3CXn4Xn5C), wherein Xn1 can be any amino acid that does not naturally form a covalent crosslinking bond, wherein Xn2 is one of:
- A, R, N, D, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, or V, wherein Xn3 can be any amino acid, wherein Xn4 can be any amino acid, and wherein Xn5 can be any amino acid.
An amino acid hinge region comprising a sequence of SEQ ID NO:
- 2 (Xn1 Xn2 Xn3 Xn4Xn5 Xn6CXn7Xn8CXn9Xn10C), wherein Xn1 can be any m amino acids, wherein m is any number of amino acids of any type, wherein Xn2 can be any amino acid, wherein Xn3 can be any amino acid, wherein Xn4 can be any amino acid, wherein Xn5 can be any amino acid, wherein Xn6 can be any amino acid other than a cysteine, wherein X17 can be any amino acid, wherein Xn8 can be any amino acid, wherein Xn9 can be any amino acid, and wherein Xn10 can be any amino acid.
An amino acid hinge region comprising:
- a core hinge sequence of at least one of:
- CVECPPCP (SEQ ID NO:
- 57), CPPCPPC (SEQ ID NO:
- 52), or CPPCPPCPPC (SEQ ID NO:
- 54), or CPPCVECPPC (SEQ ID NO:
- 53) linked to;
- an upper hinge sequence of ELKTPLGDTTHT (SEQ ID NO:
- 48) or EPKSSDKTHT (SEQ ID NO:
- 46).
An amino acid hinge region for an antibody comprising:
- an upper hinge region that comprises no amino acids capable of crosslinking with a corresponding amino acid;
- and
- a core hinge region connected to a C-terminus of the upper hinge region, wherein the core hinge region comprises at least three cysteines per strand.
The amino acid hinge region of 52, wherein the amino acid hinge region further comprises a lower hinge or extension region connected C-terminal to the core hinge region, wherein the lower hinge or extension sequence is at least one of:
- APPVAGP (SEQ ID NO:
- 60), APELLGGP (SEQ ID NO:
- 58), and/or GGGSSGGGSG (SEQ ID NO:
- 59).
The amino acid hinge region of 52, wherein the upper hinge region comprises no cysteines that crosslink within the upper hinge region.
A minibody comprising a core hinge region, wherein the core hinge region comprises at least three cysteines per strand forming at least three disulfide bonds within the core hinge region.
A minibody comprising a sequence Xn1CXn2Xn3CXn4Xn5C (SEQ ID NO:
- 3), wherein SEQ ID NO:
- 3 is located as the core hinge region of the minibody, and wherein Xn1 can be any amino acid or no amino acid, Xn2 can be any amino acid, Xn3 can be any amino acid, Xn4 can be any amino acid, and Xn5 can be any amino acid.
A variant minibody hinge comprising:
- a first altered amino acid position, wherein the first altered position is an amino acid that in a native antibody hinge would be a cysteine, and has been altered in the first altered position so that it does not form a disulfide bond;
- and
- at least three cysteines per strand C-terminal to the first altered amino acid position.
Dependencies are inferred from the claim text.