Nucleic acids encoding GARP-TGF-beta 1 antibodies

Patent metadata

Field	Value
Publication number	US-10875914-B2
Application number	US-201916409679-A
Country	US
Kind code	B2
Filing date	May 10, 2019
Priority date	May 11, 2017
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

The present invention relates to antibodies and antigen binding fragments thereof, which bind to a complex of GARP and TGF-β1, particularly a complex of human GARP and human TGF-β1. These antibodies and antigen binding fragments exhibit a combination of advantageous properties including high affinity antigen binding and the ability to inhibit the release of active TGF-β from regulatory T cells. The antibodies and antigen binding fragments of the present invention are relatively resistant to deamidation, isomerization and oxidation, such that they display improved stability.

First claim

The invention claimed is:

1. A nucleic acid encoding a recombinant antibody or antigen binding fragment thereof, which binds to a complex of human glycoprotein A repetitions predominant (GARP) and TGF-β1, wherein the antibody or antigen binding fragment thereof comprises
a heavy chain variable domain (VH), wherein:

the VH CDR3 comprises the amino acid sequence YEWETVVVGDLMYEYEY (SEQ ID NO:13),
the VH CDR2 comprises the amino acid sequence RIDPEDAGTKYAQKFQG (SEQ ID NO:12), and
the VH CDR1 comprises the amino acid sequence SYYID (SEQ ID NO:4); and
a light chain variable domain (VL), wherein:

the VL CDR3 comprises the amino acid sequence QQYASVPVT (SEQ ID NO:11),
the VL CDR2 comprises the amino acid sequence GASRLKT (SEQ ID NO:10), and
the VL CDR1 comprises the amino acid sequence QASQSISSYLA (SEQ ID NO:9).

2. The nucleic acid of claim 1 , wherein antibody or antigen binding fragment comprises a VH comprising the amino acid sequence of SEQ ID NO:14 and a VL comprising the amino acid sequence of SEQ ID NO:15.

3. The nucleic acid of claim 2 , which comprises the sequences of SEQ ID NO:18 and SEQ ID NO:19.

4. The nucleic acid of claim 2 , wherein the antibody or antigen binding fragment further comprises a CH1 domain, hinge region, CH2 domain and/or CH3 domain of a human IgG.

5. The nucleic acid of claim 4 , wherein the human IgG is IgG1.

6. The nucleic acid of claim 4 , wherein the human IgG is IgG4.

7. The nucleic acid of claim 6 , wherein the human IgG4 has the substitution S228P in the CH3 domain.

8. The nucleic acid of claim 1 , wherein antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:16 and a light chain comprising the amino acid sequence of SEQ ID NO:17.

9. The nucleic acid of claim 8 , which comprises the sequences of SEQ ID NO:20 and SEQ ID NO:21.

10. An expression vector comprising the nucleic acid of claim 1 operably linked to regulatory sequences which permit expression of an antibody, antigen binding fragment, heavy chain variable domain, or light chain variable domain in a host cell or cell-free expression system.

11. A host cell or cell-free expression system containing the expression vector of claim 10 .

12. A method of producing a recombinant antibody or antigen binding fragment thereof, comprising culturing the host cell or cell-free expression system of claim 11 under conditions which permit expression of the antibody or antigen binding fragment; and recovering the expressed antibody or antigen binding fragment.

13. An expression vector comprising the nucleic acid of claim 2 operably linked to regulatory sequences which permit expression of an antibody, antigen binding fragment, heavy chain variable domain, or light chain variable domain in a host cell or cell-free expression system.

14. A host cell or cell-free expression system containing the expression vector of claim 13 .

15. A method of producing a recombinant antibody or antigen binding fragment thereof, comprising culturing the host cell or cell-free expression system of claim 14 under conditions which permit expression of the antibody or antigen binding fragment; and recovering the expressed antibody or antigen binding fragment.

16. An expression vector comprising the nucleic acid of claim 8 operably linked to regulatory sequences which permit expression of an antibody in a host cell or cell-free expression system.

17. A host cell or cell-free expression system containing the expression vector of claim 16 .

18. A method of producing a recombinant antibody, comprising culturing the host cell or cell-free expression system of claim 17 under conditions which permit expression of the antibody; and recovering the expressed antibody.

Assignees

• Argenx Bvba
• Univ Catholique Louvain

Inventors

• Van Der Woning Sebastian
• Borgions Filip
• Dreier Torsten
• Mariën Lore
• De Boeck Gitte
• Liénart Stëphanie
• Lucas Sophie
• Coulie Pierre

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• C07K16/28 Primary

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K2317/94

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