Treatment method

Patent metadata

Field	Value
Publication number	US-11013801-B2
Application number	US-201615371891-A
Country	US
Kind code	B2
Filing date	Dec 7, 2016
Priority date	Dec 9, 2015
Publication date	May 25, 2021
Grant date	May 25, 2021

Abstract

The present invention relates to methods of treating a disease, and methods for reduction of the formation of anti-drug antibodies (ADAs) in response to the administration of a therapeutic agent. The invention further relates to methods of treating a disease, particularly a B-cell proliferative disorder, and methods for reduction of adverse effects in response to the administration of a therapeutic agent, particularly a T-cell activating therapeutic agent.

First claim

The invention claimed is:

1. A method of treating a carcinoembryonic antigen (CEA)-expressing cancer in a subject, the method comprising a treatment regimen comprising:
(i) administering to the subject a Type II anti-CD20 antibody comprising a heavy chain variable region comprising a heavy chain CDR (HCDR) 1 comprising the amino acid sequence of SEQ ID NO: 4, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a light chain variable region comprising a light chain CDR (LCDR) 1 comprising the amino acid sequence of SEQ ID NO: 7, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 9, and consecutively, after a period of time,
(ii) administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CEA,
wherein the period of time between step (i) and step (ii) is sufficient for the Type II anti-CD20 antibody to reduce the number of B cells in the subject.

2. The method of claim 1 , wherein the treatment regimen effectively reduces the formation of anti-drug antibodies (ADAs) in the subject against the therapeutic agent, as compared to a corresponding treatment regimen without the administration of the Type II anti-CD20 antibody.

3. The method of claim 1 , wherein the treatment regimen effectively reduces cytokine release in the subject associated with the administration of the therapeutic agent, as compared to a corresponding treatment regimen without the administration of the Type II anti-CD20 antibody.

4. The method of claim 1 , wherein the Type II anti-CD20 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 10 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

5. The method of claim 1 , wherein the Type II anti-CD20 antibody is an IgG antibody, and wherein at least about 40% of the N-linked oligosaccharides in the Fc region of the Type II anti-CD20 antibody are non-fucosylated.

6. The method of claim 4 , wherein the Type II anti-CD20 antibody is obinutuzumab.

7. The method of claim 1 , wherein the bispecific antibody comprises a CEA-binding moiety comprising a heavy chain variable region comprising an HCDR 1 comprising the amino acid sequence of SEQ ID NO: 14, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 16; and a light chain variable region comprising an LCDR 1 comprising the amino acid sequence of SEQ ID NO: 17, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 19.

8. The method of claim 1 , wherein the bispecific antibody comprises a CD3-binding moiety comprising a heavy chain variable region comprising an HCDR 1 comprising the amino acid sequence of SEQ ID NO: 32, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 33, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 34; and a light chain variable region comprising an LCDR 1 comprising the amino acid sequence of SEQ ID NO: 35, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 36, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 37.

9. The method of claim 7 , wherein the CEA-binding moiety comprises
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 21.

10. The method of claim 5 , wherein the IgG antibody is an IgG 1 antibody.

11. The method of claim 1 , wherein the CD3 is CD3ε.

12. The method of claim 1 , wherein the bispecific antibody comprises a CD3-binding moiety and a CEA-binding moiety, wherein:
(i) the CD3-binding moiety comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 39; and
(ii) the CEA-binding moiety comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 21.

13. The method of claim 1 , wherein:
(a) the bispecific antibody comprises a CD3-binding moiety and a CEA-binding moiety, wherein:
(i) the CD3-binding moiety comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 39; and
(ii) the CEA-binding moiety comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 21; and

(b) the Type II anti-CD20 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 10 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

14. The method of claim 8 , wherein the CD3-binding moiety comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 39.

15. A method of treating a CD20-positive B-cell disorder in a subject, the method comprising a treatment regimen comprising:
(i) administering to the subject a Type II anti-CD20 antibody comprising a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a light chain variable region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO: 7, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 9, and consecutively, after a period of time,
(ii) administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CD20,
wherein the period of time between step (i) and step (ii) is sufficient for the Type II anti-CD20 antibody to reduce the number of B cells in the subject.

16. The method of claim 15 , wherein the CD3 is CD3c.

17. The method of claim 15 , wherein the treatment regimen effectively reduces the formation of ADAs in the subject against the therapeutic agent, as compared to a corresponding treatment regimen without the administration of the Type II anti-CD20 antibody.

18. The method of claim 15 , wherein the treatment regimen effectively reduces cytokine release in the subject associated with the administration of the therapeutic agent, as compared to a corresponding treatment regimen without the administration of the Type II anti-CD20 antibody.

19. The method of claim 15 , wherein the Type II anti-CD20 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 10 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

20. The method of claim 15 , wherein the Type II anti-CD20 antibody is an IgG antibody, and wherein at least about 40% of the N-linked oligosaccharides in the Fc region of the Type II anti-CD20 antibody are non-fucosylated.

21. The method of claim 20 , wherein the IgG antibody is an IgG 1 antibody.

22. The method of claim 19 , wherein the Type II anti-CD20 antibody is obinutuzumab.

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Assignees

• Hoffmann La Roche

Inventors

• Bacac Marina
• Evers Stefan
• Klein Christian
• Pisa Pavel
• Rossmann Eva
• Saro Jose
• Umana Pablo

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• C07K2319/24

  containing a MBP (maltose binding protein)-tag · CPC title

• C07K16/3007

  Carcino-embryonic Antigens · CPC title

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title