Antibody conjugates and methods of making and using the same

Patent metadata

Field	Value
Publication number	US-11208632-B2
Application number	US-201715495431-A
Country	US
Kind code	B2
Filing date	Apr 24, 2017
Priority date	Apr 26, 2016
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

Abstract

Antibodies that include a sulfatase motif-containing tag in a constant region of an immunoglobulin (Ig) light chain polypeptide are disclosed. The sulfatase motif can be converted by a formylglycine-generating enzyme (FGE) to produce a formylglycine (fGly)-modified Ig light chain polypeptide. An fGly-modified Ig light chain polypeptide of the antibody can be covalently and site-specifically bound to a moiety of interest to provide an antibody conjugate. The disclosure also encompasses methods of production of such tagged Ig light chain polypeptides, fGly-modified Ig light chain polypeptides, and antibody conjugates, as well as methods of use of same.

First claim

What is claimed is:

1. An antibody comprising an immunoglobulin (Ig) kappa light chain polypeptide comprising, in a constant region, an amino acid sequence selected from
the group consisting of: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 31, SEQ ID NO: 37, SEQ ID NO: 44, and SEQ ID NO: 45.

2. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 2.

3. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 4.

4. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 17.

5. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 18.

6. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 26.

7. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 28.

8. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 31.

9. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 37.

10. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 44.

11. The antibody of claim 1 , wherein the Ig kappa light chain polypeptide comprises, in the constant region, the amino acid sequence of SEQ ID NO: 45.

12. The antibody of claim 1 , wherein the antibody specifically binds a tumor antigen on a cancer cell.

13. A recombinant nucleic acid comprising a nucleotide sequence encoding the Ig kappa light chain polypeptide of the antibody of claim 1 .

14. A recombinant expression vector comprising the nucleic acid of claim 13 , wherein the Ig kappa light chain polypeptide-encoding nucleotide sequence is operably linked to a promoter.

15. A recombinant expression vector comprising a nucleotide sequence encoding an Ig heavy chain polypeptide of the antibody of claim 1 .

16. A host cell genetically modified to express the antibody of claim 1 .

17. The host cell of claim 16 , genetically modified to express a formylglycine generating enzyme (FGE), in a manner sufficient to convert the Ig kappa light chain polypeptide into an fGly-modified Ig kappa light chain polypeptide.

18. The host cell of claim 16 , wherein the host cell is a mammalian cell.

19. A formulation comprising: the antibody of claim 1 and a pharmaceutically acceptable excipient.

Assignees

• Scherer Technologies Llc R P

Inventors

• Kim Yun Cheol
• Huang Chao Bai
• Rabuka David

Classifications

• C07K2319/40

  containing a tag for immunodetection, or an epitope for immunisation · CPC title

• C07K2317/515

  Complete light chain, i.e. VL + CL · CPC title

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title