Mutant antibodies and conjugation thereof

1. An antibody or antigen binding portion thereof comprising a mammalian constant light domain;

wherein said mammalian constant light domain comprises a sequence selected from the group consisting of: SEQ ID NO: 37; SEQ ID NO: 38; SEQ ID NO: 41; SEQ ID NO: 40; SEQ ID NO: 54; SEQ ID NO: 49; SEQ ID NO: 50; and SEQ ID NO: 42;

wherein a K located at a position corresponding to residue 80 comprises a side chain with an ε-amino group covalently attached to a linker,

and pharmaceutically acceptable salts, stereoisomers, tautomers, and solvates, thereof.

2. The antibody or antigen binding portion thereof as claimed in claim 1 , further comprising a residue selected from the group consisting of V, I and L at a position corresponding to residue 42 of.

3. The antibody or antigen binding portion thereof as claimed in claim 1 , wherein the residues at positions corresponding to residues 42 and 43 of are not in α-helical formation.

4. The antibody or antigen binding portion thereof as claimed in claim 1 , wherein the mammalian antibody constant domain is a humanized or human domain.

5. The antibody or antigen binding portion thereof as claimed in claim 1 , wherein the constant domain is connected to an antibody variable domain.

6. The antibody or antigen binding portion thereof as claimed in claim 1 , wherein the linker comprises a formula selected from the group consisting of X 1 -Y 1 -Z 1 , X 1 -Φ-Y 1 -Z 1 , and X 1 -Y 1 -Φ-Z, wherein Φ is a cleavable group, X 1 is a group covalently connectable to at least one Effector Moiety, Y 1 is a linear or branched connecting chain, and Z is a group covalently connected to the ε-amino group of the side chain of K that is located at a position corresponding to residue 80 of.

7. The antibody or antigen binding portion thereof as claimed in claim 6 , wherein the cleavable group Φ is present, and is of the formula

wherein the wavy line and parallel line each indicate a point of attachment to either the X 1 , Y 1 or Z 1 group as appropriate.

8. The antibody or antigen binding portion thereof as claimed in claim 6 , wherein the linker is selected from the group consisting of:

wherein m, n, j and k are each independently a range whose lower limits are selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20, and whose upper limit is selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, and wherein the overall length of the linker does not exceed 200 atoms.

9. The antibody or antigen binding portion thereof as claimed in claim 6 , wherein the Effector Moiety is a therapeutic agent, protein, peptide, nucleic acid, aptamer, small molecule, protein agonist, protein antagonist, metabolic regulator, hormone, toxin, growth factor, or diagnostic agent.

10. The antibody or antigen binding portion thereof as claimed in claim 9 , wherein the Effector Moiety is a toxin, and comprises the formula:

or a pharmaceutically acceptable salt or solvate thereof, wherein, independently for each occurrence,

W 2 is

R 11 is

Y 2 is -C 2 -C 20 alkylene-, —C 2 -C 20 heteroalkylene-; —C 3 -C 8 carbocyclo-, -arylene-, -C 3 -C 8 heterocyclo-, —C 1 -C 10 alkylene-arylene-, -arylene-C 1 -C 10 alkylene-, —C 1 -C 10 alkylene-(C 3 -C 8 carbocyclo)-, —(C 3 -C 8 carbocyclo)-C 1 -C 10 alkylene-, —C 1 -C 10 alkylene-(C 3 -C 8 heterocyclo)- or —(C 3 -C 8 heterocyclo)-C 1 -C 10 alkylene-;

Z 2 is

R 12 is hydrogen, C 1 -C 8 alkyl or C 1 -C 8 haloalkyl;

R 13A and R 13B are either of the following:

(i) R 13A is hydrogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 3 -C 8 carbocyclyl, C 1 -C 10 heterocyclyl, aryl, heteroaralkyl, aralkyl or halogen; and

R 13B is C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 3 -C 8 carbocyclyl, C 1 -C 10 heterocyclyl, aryl, heteroaralkyl or aralkyl or halogen; or

(ii) R 13A and R 13B taken together are C 2 -C 8 alkylene or C 1 -C 8 heteroalkylene;

R 14A and R 14B are either of the following:

(i) R 14A is hydrogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 3 -C 8 carbocyclyl, C 1 -C 10 heterocyclyl, aryl, heteroaralkyl or aralkyl; and

R 14B is hydrogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 3 -C 8 carbocyclyl, C 1 -C 10 heterocyclyl, aryl, heteroaralkyl or aralkyl; or

(ii) R 14A and R 14B taken together are C 2 -C 8 alkylene or C 1 -C 8 heteroalkylene;

R 15 is

 C 1 -C 10 heterocyclyl, C 3 -C 8 carbocycly and C 6 -C 14 aryl optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of —C 1 -C 8 alkyl, —C 1 -C 8 alkyl-N(R′) 2 , —C 1 -C 8 alkyl-C(O)R′, —C 1 -C 8 alkyl-C(O)OR′—O—(C 1 -C 8 alkyl), —C(O)R′, —OC(O)R′, —C(O)OR′, —C(O)N(R′) 2 , —NHC(O)R′, —S(O) 2 R′, —S(O)R′, —OH, halogen, —N 3 , —N(R′) 2 , —CN, —NHC(═NH)NH 2 , —NHCONH 2 , —S(═O) 2 R′ and —SR′, wherein each R′ is independently selected from the group consisting of hydrogen, C 1 -C 8 alkyl and unsubstituted aryl, or two R′ can, together with the nitrogen to which they are attached, form a C 1 -C 10 heterocyclyl;

or R 15 is

 optionally substituted with 1, 2, 3, 4 or 5 groups independently selected from the group consisting of C 1 -C 8 alkyl, —C 1 -C 8 alkyl-N(R′) 2 , —C 1 -C 8 alkyl-C(O)R′, —C 1 -C 8 alkyl-C(O)OR′, —O—(C 1 -C 8 alkyl), —C(O)R′, —OC(O)R′, —C(O)OR′, —C(O)N(R′) 2 , —NHC(O)R′, —S(O) 2 R′, —S(O)R′, —OH, halogen, —N 3 , —N(R′) 2 , —CN, —NHC(═NH)NH 2 , —NHCONH 2 , —S(═O) 2 R′, —SR and arylene-R′, wherein each R′ is independently selected from the group consisting of hydrogen, C 1 -C 8 alkyl, C 1 -C 8 heterocyclyl, C 1 -C 10 alkylene-C 3 -C 8 heterocyclyl and aryl, or two R′ can, together with the nitrogen to which they are attached, form a C 1 -C 10 heterocyclyl;

R 16 is hydrogen, —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl or -C 1 -C 8 haloalkyl;

R 22 is hydrogen, C 1 -C 4 alkyl, C 1 -C 10 heterocyclyl or C 6 -C 14 aryl;

R 23 is C 1 -C 10 heterocyclyl; and

R 17 is independently selected for each occurrence from the group consisting of F, Cl, I and Br;

R 20 is -aryl, —C 1 -C 10 alkylene-aryl, where aryl on R 10 comprising aryl is substituted with [R 17 ] h ;

h is 5; and

X is O or S;

provided that when R 13A is hydrogen X is S.

11. The antibody or antigen binding portion thereof as claimed in claim 9 , wherein the Effector Moiety is a toxin, and is selected from the group consisting of

12. The antibody as claimed in claim 1 , wherein the constant light domain is a kappa domain (CLk).

13. The antibody as claimed in claim 1 , wherein the constant light domain is a lambda domain (CLA).

14. A composition comprising multiples of the antibody or antigen binding portion thereof as claimed in claim 1 , wherein at least about 70% of the antibodies or antigen binding portions thereof comprises the linker covalently attached to the ε-amine group of the side chain of K that is located at a position corresponding to residue 80.

15. The antibody or antigen binding portion thereof as claimed in claim 1 , wherein the antibody is a full length antibody, Fab, Fab′, F(ab′) 2 , V H , diabody, or minibody.

16. The antibody or antigen binding portion thereof as claimed in claim 1 , wherein the antibody comprises VH and VL domains from an antibody selected from the group consisting of h38C2, rituximab, cetuximab, infliximab, adalimumab, natalizumab, omalizumab, ranibizumab, trastuzumab and palivizumab.