Multiple-variable dose regimen for treating TNFα-related disorders

• US 8,961,974 B2
• Filed: 03/28/2014
• Issued: 02/24/2015
• Est. Priority Date: 04/09/2004
• Status: Active Grant

• Current Assignee: AbbVie Biotechnology Ltd. (Puerto Rico) (Abbvie Incorporated)
• Original Assignee: AbbVie Biotechnology Ltd. (Puerto Rico) (Abbvie Incorporated)
• Inventors: Hoffman, Rebecca S., Chartash, Elliot Keith, Taylor, Lori K., Granneman, George Richard, Yan, Philip
• Primary Examiner(s): SKELDING, ZACHARY S
• Application Number:
  US14/229,722
• Publication Number:
  US 20140248277A1
• Time in Patent Office: 333 Days
• Field of Search: None
• US Class Current: 424/145.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Multiple-variable dose methods for treating TNFα-related disorders, including Crohn'"'"'s disease and psoriasis, comprising administering TNFα inhibitors, including TNFα antibodies, are described. Multiple-variable dose methods include administration of a TNF-inhibitor in an induction or loading phase followed by administration of the agent in a maintenance or treatment phase, wherein the TNF-inhibitor is administered in a higher dosage during the induction phase.

Claims

1. A multiple-variable dose method for treating ulcerative colitis in a subject in need thereof, comprising subcutaneously administering to the subject:

a first dose of 160 mg of a recombinant human anti-TNFα

antibody administered to the subject within a day; and

a second dose of 80 mg of the antibody administered to the subject within a day, wherein the second dose is administered two weeks following administration of the first dose;

wherein the antibody comprises;

a heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

8;

a CDR2 comprising the amino acid sequence of SEQ ID NO;

6; and

a CDR3 comprising the amino acid sequence of SEQ ID NO;

4; and

a light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

7;

a CDR2 comprising the amino acid sequence of SEQ ID NO;

5; and

a CDR3 comprising the amino acid sequence of SEQ ID NO;

3.

2. The method of claim 1, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

2, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO;

1.

3. The method of claim 2, wherein the heavy chain comprises an IgG1 heavy chain constant region and the light chain comprises a kappa light chain constant region.

4. The method of claim 3, wherein the antibody is adalimumab.

5. The method of claim 1, wherein the method further comprises administering to the subject a subsequent subcutaneous injection of 40 mg of the antibody two weeks following administration of the second dose.

6. The method of claim 5, wherein the method further comprises administering to the subject additional subsequent subcutaneous injections of 40 mg of the antibody, wherein the subsequent subcutaneous injections are administered two weeks apart.

7. The method of claim 5, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

2, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO;

1.

8. The method of claim 6, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

2, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO;

1.

9. The method of claim 7, wherein the heavy chain comprises an IgG1 heavy chain constant region and the light chain comprises a kappa light chain constant region.

10. The method of claim 8, wherein the heavy chain comprises an IgG1 heavy chain constant region and the light chain comprises a kappa light chain constant region.

11. The method of claim 9, wherein the antibody is adalimumab.

12. The method of claim 10, wherein the antibody is adalimumab.

13. The method of claim 1, wherein each subcutaneous injection is administered to the subject using a prefilled syringe.

14. The method of claim 5, wherein each subcutaneous injection is administered to the subject using a prefilled syringe.

15. A multiple-variable dose method for treating ulcerative colitis in a subject in need thereof, comprising subcutaneously administering to the subject:

a first dose of 160 mg of a recombinant human anti-TNFα

antibody administered as a set of four injections of 40 mg of the antibody administered to the subject within a day; and

a second dose of 80 mg of the antibody administered as a set of two injections of 40 mg of the antibody administered to the subject within a day, wherein the second dose is administered two weeks following administration of the first dose;

wherein the antibody comprises;

a heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

8;

a CDR2 comprising the amino acid sequence of SEQ ID NO;

6; and

a CDR3 comprising the amino acid sequence of SEQ ID NO;

4; and

a light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

7;

a CDR2 comprising the amino acid sequence of SEQ ID NO;

5; and

a CDR3 comprising the amino acid sequence of SEQ ID NO;

3.

16. The method of claim 15, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

2, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO;

1.

17. The method of claim 16, wherein the heavy chain comprises an IgG1 heavy chain constant region and the light chain comprises a kappa light chain constant region.

18. The method of claim 17, wherein the antibody is adalimumab.

19. The method of claim 15, wherein the method further comprises administering to the subject a subsequent subcutaneous injection of 40 mg of the antibody two weeks following administration of the second dose.

20. The method of claim 19, wherein the method further comprises administering to the subject additional subsequent subcutaneous injections of 40 mg of the antibody, wherein the subsequent subcutaneous injections are administered two weeks apart.

21. The method of claim 19, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

2, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO;

1.

22. The method of claim 20, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

2, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO;

1.

23. The method of claim 21, wherein the heavy chain comprises an IgG1 heavy chain constant region and the light chain comprises a kappa light chain constant region.

24. The method of claim 22, wherein the heavy chain comprises an IgG1 heavy chain constant region and the light chain comprises a kappa light chain constant region.

25. The method of claim 23, wherein the antibody is adalimumab.

26. The method of claim 24, wherein the antibody is adalimumab.

27. The method of claim 15, wherein each subcutaneous injection is administered to the subject using a prefilled syringe.

28. The method of claim 19, wherein each subcutaneous injection is administered to the subject using a prefilled syringe.