Method of treating lupus by administering humanized anti-CXCR5 (C-X-C motif chemokine receptor 5) antibodies

Patent metadata

Field	Value
Publication number	US-10842869-B2
Application number	US-201815927675-A
Country	US
Kind code	B2
Filing date	Mar 21, 2018
Priority date	Mar 22, 2017
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

This disclosure provides anti-CXCR5 antibodies and their use in the amelioration, treatment, or prevention of lupus. The disclosure also provides prophylactic, immunotherapeutic, and diagnostic compositions comprising an anti-CXCR5 antibody, and the use of such anti-CXCR5 antibodies in methods of preventing or treating lupus in mammals, including humans.

First claim

The invention claimed is:

1. A method of treating lupus in a patient, comprising administering to the patient a therapeutically effective amount of an antibody or fragment thereof that specifically binds to the extracellular domain of human C—X—C Motif Chemokine Receptor 5 (CXCR5), wherein the antibody or fragment thereof comprises:
(a) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 11, and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 12;
(b) the amino acid sequences of RSSKSLLHSSGKTYLY (SEQ ID NO: 58), RMSNLAS (SEQ ID NO: 59), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID NO: 62), and IVY (SEQ ID NO: 63):
(c) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14, or SEQ ID NO: 15, and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 16;
(d) the amino acid sequences of RSSKSLLHSSGKTYLY (SEQ ID NO: 58), RLSNLAS (SEQ ID NO: 64), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID NO: 62), and IVY (SEQ ID NO: 63);
(e) the amino acid sequences of RSSKSLLHSSGKTYLY (SEQ ID NO: 58), RLSSNLAS (SEQ ID NO: 65), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID NO: 62), and IVY (SEQ ID NO: 63);
(f) a variable light chain (V L ) comprising the amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 19, or SEQ ID NO: 21, and a variable heavy chain (V H ) comprising the amino acid sequence of SEQ ID NO: 23;
(g) a variable light chain comprising the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 31, or SEQ ID NO: 32, and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 33 or SEQ ID NO: 34;
(h) the amino acid sequences of RSSKSLLHSSGKTYLY (SEQ ID NO: 58), RMSNLA (SEQ ID NO: 66), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID N: 62), and IVY (SEQ ID NO: 63);
(i) the amino acid sequences of RSSKSLLHSSGKTYLY (SEQ ID NO: 58), RLSNLA (SEQ ID NO: 67), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID NO: 62), and IVY (SEQ ID NO: 63);
(j) the amino acid sequences of RSSKSLLHSSGKTYLY (SEQ ID NO: 58), RLSSLA (SEQ ID NO: 68), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID NO: 62), and IVY (SEQ ID NO: 63);
(k) a variable light chain comprising the amino acid sequence of SEQ ID NO: 35, and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 37;
(l) a variable light chain comprising the amino acid sequence of SEQ ID NO: 39, SEQ ID NO: 41, or SEQ ID NO: 43, and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 45 or SEQ ID NO: 47;
(m) a variable light chain comprising the amino acid sequence of SEQ ID NO: 55, and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 56 or SEQ ID NO: 57; or
(n) the amino acid sequences of RSSKSLLHSSGKTYLYW (SEQ ID NO; 69), RMSNLA (SEQ ID NO: 66), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID NO: 62), and IVY (SEQ ID NO: 63); and

wherein the patient has tested positive for antinuclear antibody with a titer of >1:160, wherein the antibody or fragment thereof is administered at a dose of between 200 mg to 500 mg every four weeks.

2. The method of claim 1 , wherein the antibody or fragment thereof further comprises one or more constant region domains.

3. The method of claim 1 , wherein the antibody or fragment thereof further comprises a C H1 , C H2 , C H3 , or combinations thereof.

4. The method of claim 2 , wherein the one or more constant region domains are from an IgG antibody.

5. The method of claim 4 , wherein the IgG antibody is an IgG4 antibody.

6. The method of claim 1 , wherein the antibody or fragment thereof is a single chain Fv antibody.

7. The method of claim 1 , wherein the antibody or fragment thereof is administered to the patient subcutaneously.

8. The method of claim 1 , wherein the patient has an anti-dsDNA antibody titer of at least 11 IU/mL.

9. The method of claim 1 , wherein the patient has a systematic lupus erythematosus disease activity index of at least 4.

10. A method of treating lupus in a patient, comprising administering to the patient a therapeutically effective amount of an antibody or fragment thereof that specifically binds to the extracellular domain of human CXCR5, wherein the antibody or fragment thereof comprises a variable light chain comprising the amino acid sequence of SEQ ID NO: 32, and a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 33; and
wherein the patient has tested positive for antinuclear antibody with a titer of ≥1:160, wherein the antibody or fragment thereof is administered at a dose of 200 mg to 500 mg every four weeks.

11. The method of claim 10 , wherein the antibody or fragment thereof is administered to the patient subcutaneously.

12. The method of claim 10 , wherein the patient has an anti-dsDNA antibody titer of at least 11 IU/mL.

13. The method of claim 10 , wherein the patient has a systematic lupus erythematosus disease activity index of at least 4.

14. A method of treating lupus in a patient, comprising administering to the patient a therapeutically effective amount of an antibody or fragment thereof that specifically binds to the extracellular domain of human CXCR5, wherein the antibody or fragment thereof comprises the amino acid sequences of RSSKSLLHSSGKTYLY (SEQ ID NO: 58), RLSSLA (SEQ ID NO: 68), MQHLEYPYT (SEQ ID NO: 60), GFSLIDYGVN (SEQ ID NO: 61), VIWGDGTTY (SEQ ID NO: 62), and IVY (SEQ ID NO: 63); and
wherein the patient has tested positive for antinuclear antibody with a titer of ≥1:160, wherein the antibody or fragment thereof is administered at a dose of 200 mg to 500 mg every four weeks.

15. The method of claim 14 , wherein the antibody or fragment thereof is administered to the patient subcutaneously.

16. The method of claim 14 , wherein the patient has an anti-dsDNA antibody titer of at least 11 IU/mL.

17. The method of claim 14 , wherein the patient has a systematic lupus erythematosus disease activity index of at least 4.

Assignees

• Sanofi Sa

Inventors

• Ming Jeffrey
• Zilberstein Moshe E
• Karimi Anderesi Roghieh

Classifications

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title

• A61K2039/55

  characterised by the host/recipient, e.g. newborn with maternal antibodies · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title