Administration of alpha4beta7 hetero-dimer-specific antibody

Patent metadata

Field	Value
Publication number	US-9914779-B2
Application number	US-201214360087-A
Country	US
Kind code	B2
Filing date	Nov 21, 2012
Priority date	Nov 23, 2011
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

There is provided a method of treating a subject afflicted with a condition that is associated with inappropriate trafficking of cells expressing alpha4beta7 to the gastrointestinal tract, comprising administering to the subject an alpha4beta7 heterodimer specific antibody in an amount and at an interval sufficient to ameliorate the condition.

First claim

What is claimed is:

1. A method of treating a subject afflicted with a condition that is associated with inappropriate trafficking of cells expressing alpha4beta7 to the gastrointestinal tract, wherein the condition is inflammatory bowel disease, comprising administering to the subject an alpha4beta7 heterodimer specific antibody 18A11 in an amount and at an interval selected from the group consisting of:
(a) 5-14 mg every 7-21 days;
(b) 15-54 mg every 14-56 days;
(c) 55-149 mg every 43-126 days;
(d) 150-299 mg every 112-147 days; and
(e) 300-1000 mg every 126-224 days;
wherein 18A11 is an isolated, alpha4beta7 heterodimer-specific antigen binding protein having a heavy chain variable region comprising CDR1, CDR2 and CDR3 from SEQ ID NO:5, and a light chain variable region comprising CDR1, CDR2 and CDR3 from SEQ ID NO:2.

2. The method of claim 1 , wherein the amount and interval are selected from the group consisting of:
(a) 5-10 mg every 11-17 days;
(b) 15-30 mg every 30-50 days;
(c) 55-85 mg every 75-95 days;
(d) 160-260 mg every 120-132 days; and
(e) 300-700 mg every 165-−185 days.

3. The method of claim 1 , wherein the amount and interval are selected from the group consisting of:
(a) 7 mg every 2 weeks;
(b) 21 mg every 6 weeks;
(c) 70 mg every 12 weeks;
(d) 210 mg every 18 weeks; and
(e) 420 mg every six months.

4. The method of claim 1 , wherein 18A11 is an isolated, alpha4beta7 heterodimer-specific antigen binding protein wherein the heavy chain variable region is at least 90% identical to SEQ ID NO:5, and the light chain variable region is at least 90% identical to SEQ ID NO:2.

5. The method of claim 1 , wherein 18A11 further comprises a light chain constant region (SEQ ID NO:7) and a heavy chain constant region (SEQ IN NO:8).

6. The method of claim 5 , wherein 18A11 differs in amino acid sequence from the amino acid sequences of SEQ ID NO:2 and 5 by the substitution, insertion or deletion of from 1 to 10 amino acids in an 18A 11 variable region.

7. The method of claim 5 , wherein 18A11 differs in amino acid sequence from the amino acid sequences of SEQ ID NO:7 and 8 by the substitution, insertion or deletion of from 1 to 10 amino acids in an 18A11 constant region of 18A11.

8. The method of claim 5 wherein the 18A11 incorporate one or more modifications selected from the group consisting of conversion of some, most or substantially all of an N-terminal amino acid to pyroglutamic acid; and removal (either post-translationally or by recombinant technology) of one, two, three, four or five N-terminal and/or C-terminal amino acids.

9. A method of treating a subject afflicted with a condition that is associated with inappropriate trafficking of cells expressing alpha4beta7 to the gastrointestinal tract, wherein the condition is inflammatory bowel disease, comprising administering to the subject an amount of an alpha4beta7 heterodimer specific antibody 18A11 in an amount and at an interval sufficient to achieve and/or maintain a receptor occupancy of at least about 75%; wherein 18A11 is an isolated, alpha4beta7 heterodimer-specific antigen binding protein having a heavy chain variable region comprising CDR1, CDR2 and CDR3 from SEQ ID NO:5, and a light chain variable region comprising CDR1, CDR2 and CDR3 from SEQ ID NO:2.

10. The method of claim 9 , wherein the receptor occupancy achieved is at least about 80%.

11. The method of claim 9 , wherein the receptor occupancy achieved is at least about 85%.

12. The method of claim 9 , wherein the receptor occupancy achieved is at least about 90%.

13. The method of claim 9 , wherein the receptor occupancy achieved is at least about 95%.

14. The method of claim 9 , wherein the receptor occupancy achieved is at least about 99%.

15. A method of treating a subject afflicted with a condition that is associated with inappropriate trafficking of cells expressing alpha4beta7 to the gastrointestinal tract, wherein the condition is inflammatory bowel disease, comprising administering to the subject an amount of an alpha4beta7 heterodimer specific antibody 18A11 in an amount and at an interval sufficient to achieve and/or maintain a quantity of heterodimer-specific antibody per volume of serum of between 10 ng/ml and 1000 ng/ml; wherein 18A11 is an isolated, alpha4beta7 heterodimer-specific antigen binding protein having a heavy chain variable region comprising CDR1, CDR2 and CDR3 from SEQ ID NO:5, and a light chain variable region comprising CDR1, CDR2 and CDR3 from SEQ ID NO:2.

16. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is at least 10 ng/ml.

17. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is selected from the group consisting of: at least 25 ng/ml; at least 50 ng/ml; at least 60 ng/ml; at least 70 ng/ml; at least 75 ng/ml; and at least 80 ng/ml.

18. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is between 85 ng/ml and 100 ng/ml.

19. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is between 70 ng/ml and 150 ng/ml.

20. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is between 50 ng/ml and 250 ng/ml.

21. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is between 40 ng/ml and 500 ng/ml.

22. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is between 25 ng/ml and 750 ng/ml.

23. The method of claim 15 , wherein the quantity of heterodimer-specific antibody per volume of serum is between 10 ng/ml and 1,000 ng/ml.

Assignees

• Amgen Inc

Inventors

• Borie Dominique Christian
• Hsu Hailing
• Pan Wei-Jian
• Rees William
• Sullivan Barbara Anne

Classifications

• G01N2800/065

  Bowel diseases, e.g. Crohn, ulcerative colitis, IBS · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• C07K2317/90

  characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin · CPC title

• C07K16/2839 Primary

  against the integrin superfamily · CPC title

• A61K2039/545

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