Claims for Patent: 9,334,320

Summary for Patent: 9,334,320

Title:	Methods of treating moderate to severe hidradenitis suppurativa with anti-TNFalpha antibody
Abstract:	The invention provides methods, uses and compositions for the treatment of hidradenitis suppurativa. The invention describes methods and uses for treating hidradenitis suppurativa, wherein a TNF.alpha. inhibitor, such as a human TNF.alpha. antibody, or antigen-binding portion thereof, is used to treat hidradenitis suppurativa in a subject. Also described are methods for determining the efficacy of a TNF.alpha. inhibitor for treating hidradenitis suppurativa in a subject.
Inventor(s):	Okun; Martin M. (Wilmette, IL), Harris; Thomas C. (Gurnee, IL)
Assignee:	AbbVie Biotechnology Ltd. (Hamilton, BM)
Application Number:	14/289,115
Patent Claims:	1. A method for treating a subject having moderate to severe hidradenitis suppurativa (HS), the method comprising: at week 0 administering a first loading dose of 160 mg of an isolated human anti-TNF.alpha. antibody, or antigen binding portion thereof, to the subject, wherein the first loading dose is administered as four 40 mg doses in one day or two 40 mg doses per day over two consecutive days; at week 2 administering a second loading dose of 80 mg of the human anti-TNF.alpha. antibody, or antigen binding portion thereof, to the subject, wherein the second loading dose is administered as two 40 mg doses in one day; and starting at week 4 administering a treatment dose of 40 mg of the human anti-TNF.alpha. antibody, or antigen binding portion thereof, to the subject weekly, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, comprises a variable light chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3; a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7; and comprises a variable heavy chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 8. 2. The method of claim 1, wherein the subject has HS lesions in at least two distinct anatomic areas prior to treatment. 3. The method of claim 1, wherein the subject had an inadequate response to, contraindication to, or was intolerant to oral antibiotics for treatment of their HS. 4. The method of claim 1, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, is administered subcutaneously. 5. The method of claim 1, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, dissociates from human TNF.alpha. with a K.sub.d of 1.times.10.sup.-8 M or less and a k.sub.off rate constant of 1.times.10.sup.-3 s.sup.-1 or less, both determined by surface plasmon resonance, and neutralizes human TNF.alpha. cytotoxicity in a standard in vitro L929 assay with an IC.sub.50 of 1.times.10.sup.-7 M or less. 6. The method of claim 1, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, has a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2. 7. The method of claim 1, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, is adalimumab. 8. The method of claim 1, wherein anti-TNF.alpha. antibody, or antigen binding portion thereof, is administered with at least one additional therapeutic agent. 9. The method of claim 1, wherein the subject is selected from the group consisting of a subject having HS at Hurley Stage II or III, a subject having an AN count of greater than or equal to 3 at baseline, a subject who is female, a subject who is over 40 years old, a subject who is a smoker, or any combination thereof. 10. The method of claim 1, wherein the subject achieves an HiSCR at week 12 of the treatment. 11. The method of claim 1, wherein the subject achieves at least a 30% reduction in skin pain at week 12 of the treatment. 12. A method for decreasing the number of inflammatory lesions (AN count) in a subject having moderate to severe hidradenitis suppurativa (HS), said method comprising systemically at week 0 administering a first loading dose of 160 mg of an isolated human anti-TNF.alpha. antibody, or antigen binding portion thereof, to the subject, wherein the first loading dose is administered as four 40 mg doses in one day or two 40 mg doses per day over two consecutive days; at week 2 administering a second loading dose of 80 mg of the human anti-TNF.alpha. antibody, or antigen binding portion thereof, to the subject, wherein the second loading dose is administered as two 40 mg doses in one day; and starting at week 4 administering a treatment dose of 40 mg of the human anti-TNF.alpha. antibody, or antigen binding portion thereof, to the subject weekly, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, comprises a variable light chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3; a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7; and comprises a variable heavy chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 8. 13. The method of claim 12, wherein the AN count is reduced by at least 50% reduction in the subject relative to baseline AN count. 14. The method of claim 13, wherein the subject has no increase in an abscess count and/or no increase in a draining fistula count following administration with the anti-TNF.alpha. antibody, or antigen binding portion thereof. 15. The method of claim 12, wherein the subject has no increase in an abscess count and/or no increase in a draining fistula count following administration with the anti-TNF.alpha. antibody, or antigen binding portion thereof. 16. The method of claim 12, wherein the subject has HS lesions in at least two distinct anatomic areas prior to treatment. 17. The method of claim 12, wherein the subject had an inadequate response to, contraindication to, or was intolerant to oral antibiotics for treatment of their HS. 18. The method of claim 12, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, is administered subcutaneously. 19. The method of claim 12, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, dissociates from human TNF.alpha. with a K.sub.d of 1.times.10.sup.-8 M or less and a k.sub.off rate constant of 1.times.10.sup.-3 s.sup.-1 or less, both determined by surface plasmon resonance, and neutralizes human TNF.alpha. cytotoxicity in a standard in vitro L929 assay with an IC.sub.50 of 1.times.10.sup.-7 M or less. 20. The method of claim 12, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, has a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2. 21. The method of claim 12, wherein the anti-TNF.alpha. antibody, or antigen binding portion thereof, is adalimumab. 22. The method of claim 12, wherein anti-TNF.alpha. antibody, or antigen binding portion thereof, is administered with at least one additional therapeutic agent. 23. The method of claim 12, wherein the subject is selected from the group consisting of a subject having HS at Hurley Stage II or III, a subject having an AN count of greater than or equal to 3 at baseline, a subject who is female, a subject who is over 40 years old, a subject who is a smoker, or any combination thereof. 24. The method of claim 12, wherein the subject achieves an HiSCR at week 12 of the treatment. 25. The method of claim 12, wherein the subject achieves at least a 30% reduction in skin pain at week 12 of the treatment. 26. A method for treating a subject having moderate to severe hidradenitis suppurativa (HS), the method comprising: at week 0 subcutaneously administering a first loading dose of 160 mg of adalimumab to the subject, wherein the first loading dose of adalimumab is administered as four 40 mg doses in one day or two 40 mg doses per day over two consecutive days; at week 2 subcutaneously administering a second loading dose of 80 mg of adalimumab to the subject, wherein the second loading dose of adalimumab is administered as two 40 mg doses in one day; and starting at week 4 subcutaneously administering a maintenance dose of 40 mg of adalimumab to the subject weekly. 27. The method of claim 26, further comprising subcutaneously administering to the subject 40 mg of adalimumab biweekly following a weekly maintenance dosing regimen. 28. The method of claim 26, wherein the subject has HS lesions in at least two distinct anatomic areas prior to treatment. 29. The method of claim 26, wherein the subject had an inadequate response to, contraindication to, or was intolerant to oral antibiotics for treatment of their HS. 30. The method of claim 26, wherein the subject is selected from the group consisting of a subject having HS at Hurley Stage II or III, a subject having an AN count of greater than or equal to 3 at baseline, a subject who is female, a subject who is over 40 years old, a subject who is a smoker, or any combination thereof. 31. The method of claim 26, wherein the subject achieves an HiSCR at week 12 of the treatment. 32. The method of claim 26, wherein the subject achieves at least a 30% reduction in skin pain at week 12 of the treatment. 33. The method of claim 26, wherein when a group of patients having moderate to severe HS are treated according to the treatment method of claim 26, statistically significantly more patients in said group achieve at least 30% reduction in pain relative to baseline at week 12 of said treatment, as compared to a group of patients having moderate to severe HS but treated with placebo under the same dosing scheme as in claim 26. 34. The method of claim 26, wherein when a group of patients having moderate to severe HS are treated according to the treatment method of claim 26, statistically significantly more patients in said group achieve HiSCR at week 12 of said treatment, as compared to a group of patients having moderate to severe HS but treated with placebo under the same dosing scheme as in claim 26.

Details for Patent 9,334,320

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2030-06-03
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2030-06-03
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2030-06-03
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	09/23/2014		2030-06-03
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	11/23/2015		2030-06-03
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	03/09/2016		2030-06-03
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	10/17/2016		2030-06-03