Modified polypeptides for bispecific antibody scaffolds
AssigneeMedImmune, LLC
InventorsPartha S. Chowdhury, Vaheh Oganesyan, Yariv Mazor, Nazzareno Dimasi
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Abstract
The technology relates in part to engineered antibodies. In particular, multispecific engineered antibodies. Such antibodies can be utilized for diagnostic and therapeutic applications in some aspects.
Claims75
An antibody comprising:
- (a) a modified heavy chain, wherein the modified heavy chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of a native non-cysteine amino acid to a cysteine amino acid;
- and
- (b) a modified corresponding light chain, wherein the modified light chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of a native non-cysteine amino acid to a cysteine amino acid,
- wherein the substituted cysteine of the modified heavy chain, resulting from the substitution of the native non-cysteine amino acid to the cysteine amino acid, and the substituted cysteine of the modified corresponding light chain, resulting from the substitution of the native non-cysteine amino acid to the cysteine amino acid, can form a disulphide bond.
An antibody comprising:
- (a) a modified heavy chain, wherein the CH1 region of the modified heavy chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of a native non-cysteine amino acid to a cysteine amino acid;
- and
- (b) a modified corresponding light chain, wherein the CL region of the modified light chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of a native non-cysteine amino acid to a cysteine amino acid,
- wherein the substituted cysteine of the modified heavy chain, resulting from the substitution of the native non-cysteine amino acid to the cysteine amino acid, and the substituted cysteine of the modified corresponding light chain, resulting from the substitution of the native non-cysteine amino acid to the cysteine amino acid, can form a disulphide bond.
An antibody comprising:
- (a) a modified heavy chain, wherein (i) the CH1 region of the modified heavy chain comprises a substitution of a native cysteine to a non-cysteine amino acid, and (ii) the variable region comprises a substitution of a native non-cysteine amino acid to a cysteine amino acid;
- and
- (b) a modified corresponding light chain, wherein (i) the CL region of the modified light chain comprises a substitution of a native cysteine to a non-cysteine amino acid, and (ii) the variable region comprises a substitution of a native non-cysteine amino acid to a cysteine amino acid,
- wherein the substituted cysteine of the modified heavy chain, resulting from the substitution of the native non-cysteine amino acid to the cysteine amino acid, and the substituted cysteine of the modified corresponding light chain, resulting from the substitution of the native non-cysteine amino acid to the cysteine amino acid, can form a disulphide bond.
An antibody comprising:
- (a) a modified heavy chain, wherein the modified heavy chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of at least one amino acid resulting in a protrusion and/or a cavity;
- and
- (b) a modified corresponding light chain, wherein the modified light chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of at least one amino acid resulting in a compensatory cavity and/or protrusion,
- wherein the modifications favor the interchain pairing of the modified heavy chain with the corresponding modified light chain.
The antibody of any one of the preceding claims, wherein the native cysteine is capable of forming an interchain disulphide bond.
The antibody of any one of the preceding claims, comprising a second heavy chain and a second corresponding light chain, wherein the second heavy chain and second corresponding light chain do not comprise a substitution of a native non-cysteine amino acid to a cysteine amino acid.
The antibody of any one of the preceding claims, wherein the two light chains each comprise a VL domain and a CL domain, wherein the VL domains have different amino acid sequences and the CL domains have different amino acid sequences.
The antibody of any one of the preceding claims, wherein the two heavy chains each comprise a VH domain, a CH1 domain and an Fc region, wherein the VH domains have different amino acid sequences, the CH1 domains have different amino acid sequences, and the Fc regions have different amino acid sequences.
The antibody of any one of the preceding claims, wherein the antibody specifically binds to two independent antigens or to two independent epitopes on the same antigen.
The antibody of any one of the preceding claims which is human antibody or a humanized antibody or a chimeric antibody.
A composition comprising the antibody of any one of the preceding claims and an excipient.
An isolated nucleic acid comprising a nucleotide sequence that encodes a modified light chain polypeptide, wherein the modified light chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of a native non-cysteine amino acid to a cysteine amino acid.
An isolated nucleic acid comprising a nucleotide sequence that encodes a modified light chain polypeptide, wherein the modified light chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of at least one amino acid in the CL region resulting in a cavity and/or a protrusion.
An isolated nucleic acid comprising a nucleotide sequence that encodes a modified heavy chain polypeptide, wherein the modified heavy chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of a native non-cysteine amino acid to a cysteine amino acid.
An isolated nucleic acid comprising a nucleotide sequence that encodes a modified heavy chain polypeptide, wherein the modified heavy chain comprises (i) a substitution of a native cysteine to a non-cysteine amino acid, and (ii) a substitution of at least one amino acid in the CL region resulting in a cavity and/or a protrusion.
Dependencies are inferred from the claim text.