Dosing regimens using anti-il-6 antibodies for the treatment of rheumatoid and psoriatic arthritis

Patent metadata

Field	Value
Publication number	US-2016130340-A1
Application number	US-201514876376-A
Country	US
Kind code	A1
Filing date	Oct 6, 2015
Priority date	Oct 7, 2013
Publication date	May 12, 2016
Grant date	—

Abstract

The present invention relates to therapeutic methods of using an antibody, or antigen-binding fragment thereof, which selectively binds IL-6 for the treatment or prevention of psoriatic arthritis or rheumatoid arthritis and for managing the side effects and symptoms of psoriatic or rheumatoid arthritis and therapeutic compositions for use therein comprising an antibody, or antigen-binding fragment thereof, which selectively binds IL-6 for the treatment or prevention of psoriatic or rheumatoid arthritis. The invention further relates to low dosing therapeutic regimens for treating inflammatory IL-6 associated diseases, i.e., characterized by elevated 11-6 levels such as psoriatic arthritis or rheumatoid arthritis that provided for reduced adverse side effects and improved safety. Also the invention further relates to compositions for use in low dosing therapeutic regimens for treating inflammatory IL-6 associated diseases, i.e., diseases characterized by elevated IL-6 levels such as psoriatic arthritis or rheumatoid arthritis, wherein such compositions may be administered by self-injection or by a caregiver using an autoinjector pen and a syringe containing the low dosage of anti-IL-6 antibody, e.g., 1, 5, 10, 15, 20 or 25 mg.

First claim

1 . A method for treating or preventing rheumatoid arthritis, or managing one or more of the symptoms of rheumatoid arthritis comprising administration of a composition comprising an effective amount of an anti-IL-6 antibody or antibody fragment thereof to a subject in need thereof, wherein the anti-IL-6 antibody or antibody fragment thereof comprises a variable light (V L ) chain polypeptide comprising a CDR1 sequence of SEQ ID NO:4, a CDR2 sequence of SEQ ID NO:5, and a CDR3 sequence of SEQ ID NO:6, and a variable heavy (V H ) chain polypeptide comprising a CDR1 sequence of SEQ ID NO:7, a CDR2 sequence of SEQ ID NOs:8 or 120, and a CDR3 sequence of SEQ ID NO:9, and wherein said anti-IL-6 antibody or antibody fragment thereof is administered every 4 weeks or monthly at a dosage of at most 1, 5, 10, 15, 20 or 25 mg.

2 . The method for treating or preventing rheumatoid arthritis or managing one or more of the symptoms of rheumatoid arthritis of claim 15 , comprising administration of a composition comprising an effective amount of an anti-IL-6 antibody or antibody fragment thereof to a subject in need thereof, wherein the anti-IL-6 antibody or antibody fragment thereof comprises a variable light (V L ) chain polypeptide comprising the amino acid sequence in SEQ ID NO:20, 702 or 709, and a variable heavy (V H ) chain polypeptide comprising the amino acid sequence in SEQ ID NO:18, 19, 657 or 704 and wherein said anti-IL-6 antibody or antibody fragment thereof is administered every 4 weeks or monthly at a dosage of at most 1, 5, 10, 15, 20 or 25 mg.

3 . The method for treating or preventing rheumatoid arthritis or managing one or more of the symptoms of rheumatoid arthritis of claim 1 , comprising administration of a composition comprising an effective amount of an anti-IL-6 antibody or antibody fragment thereof to a subject in need thereof, wherein the anti-IL-6 antibody or antibody fragment thereof comprises a variable light (V L ) chain polypeptide comprising the amino acid sequence in SEQ ID NO:20 or 709, and a variable heavy (V H ) chain polypeptide comprising the amino acid sequence in SEQ ID NO:18, 19, or 657, and wherein said anti-IL-6 antibody or antibody fragment thereof is administered every 4 weeks or monthly at a dosage of at most 1, 5, 10, 15, 20 or 25 mg.

4 . The method for treating or preventing rheumatoid arthritis or managing one or more of the symptoms of rheumatoid arthritis of claim 1 , comprising administration of a composition comprising an effective amount of an anti-IL-6 antibody or antibody fragment thereof to a subject in need thereof, wherein the anti-IL-6 antibody or antibody fragment thereof comprises a light chain polypeptide comprising the polypeptide having the amino acid sequence in SEQ ID NO:702 and a heavy chain comprising the polypeptide having the amino acid sequence of SEQ ID NO:704, and wherein said anti-IL-6 antibody or antibody fragment thereof is administered every 4 weeks or monthly at a dosage of at most 1, 5, 10, 15, 20 or 25 mg.

5 - 35 . (canceled)

36 . The method of claim 1 , wherein said subject has had an inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs).

37 . The method of claim 1 , wherein said subject has had an inadequate response to non-biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs).

42 . A dosage composition, or syringe or injector pen containing a single dosage of an anti-IL-6 antibody or antibody fragment which is for use in treating or preventing rheumatoid arthritis according to any of the foregoing claims, and wherein said anti-IL-6 antibody or antibody fragment comprises or consists of CDRs, variable heavy or light polypeptides or light and heavy polypeptides having the amino acid sequences as set forth in claim 1 , wherein the single dosage of said anti-IL-6 antibody or antibody fragment contained in said composition or syringe or injector pen containing same comprises at most or consists of 1, 5, 10, 15, 20, or 25 mg of said anti-IL-6 antibody or antibody fragment.

44 - 47 . (canceled)

48 . A therapeutic regimen for treating or preventing psoriatic and/or rheumatoid arthritis or managing the side effects of psoriatic and/or rheumatoid arthritis in a subject in need thereof, wherein the therapeutic regimen comprises or consists of administering a single dosage of an anti-IL-6 antibody or antibody fragment every 4 weeks or monthly using a syringe or injector pen which single dosage comprises at most or consists of 1, 5, 10, 15, 20, or 25 mg of an anti-IL-6 antibody or antibody fragment according to claim 1 .

49 . The regimen of claim 48 , wherein the anti-IL-6 antibody or antibody fragment comprises the V L polypeptide of SEQ ID NO: 20 or 709 and V H polypeptides having the amino acid sequence of SEQ ID NO: 18, 19 or 657.

49 - 53 . (canceled)

54 . The method or regimen of claim 1 or 48 , which further includes the administration of methotrexate.

55 . The method or regimen of claim 1 or 48 wherein the treated subject has developed a resistance or tolerance to methotrexate.

56 . The method or regimen of claim 1 or 48 , wherein the treated subject has previously received methotrexate.

57 . The method or regimen of any of the foregoing claims, claim 1 or 48 , wherein the treated subject has previously received another anti-IL-6 antagonist or an anti-TNF biologic.

58 . The method or regimen of any of the foregoing claims, wherein the treated subject has previously received Humira®, Remicade®, or Actemra®.

59 - 65 . (canceled)

67 . An improved therapeutic regimen for treating rheumatoid arthritis (“RA”) using an anti-IL-6 antibody, wherein the anti-IL-6 antibody comprises the light chain polypeptide of SEQ ID NO:702 and the heavy chain polypeptide of SEQ ID NO:704, and the anti-IL-6 antibody is administered weekly, every 4 weeks or monthly at a dosage of at most 1-5 mg or is administered weekly, every 4 weeks or or monthly at a dosage of at most at most 5-25 mg, and wherein such regimen provides for greater patient remission at lower dosages and/or less frequent dosing than current biologics used to treat RA.

68 . The therapeutic regimen of claim 67 , which is used to treat an RA in a patient resistant to methotrexate (“MTX”) or to another biologic.

69 . The improved therapeutic regimen of claim 67 , wherein the other biologic is Humira®, Remicade® or Actemera®.

70 . (canceled)

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L

Classifications

• A61K9/0019

  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 title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• A61K2039/505

  comprising antibodies · CPC title