Antagonists of IL-6 to prevent or treat cachexia, weakness, fatigue, and/or fever

Patent metadata

Field	Value
Publication number	US-9546213-B2
Application number	US-201113046860-A
Country	US
Kind code	B2
Filing date	Mar 14, 2011
Priority date	May 21, 2007
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

The present invention is directed to therapeutic methods using antibodies and fragments thereof having binding specificity for IL- 6 to prevent or treat cachexia, fever, weakness and/or fatigue in a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level. In another preferred embodiment, the patient's survivability or quality of life will preferably be improved.

First claim

What is claimed is:

1. A method of treating cancer-related cachexia, weakness, fever or fatigue in a patient in need thereof by administering an anti-human IL-6 antibody or anti-human IL-6 antibody fragment comprising a variable light chain polypeptide comprising an amino acid sequence selected from those of SEQ ID NO: 2 and 20 and a variable heavy chain polypeptide comprising an amino acid sequence selected from those of 3, 18, and 19, whereby the patient's cachexia, weakness, fever or fatigue is improved or returned to a normal condition.

2. The method of claim 1 , wherein the patient has advanced cancer.

3. The method of claim 1 , wherein the antibody or antibody fragment is selected from chimeric antibodies, humanized antibodies, human antibodies, rabbit antibodies, single chain antibodies selected from scFvs, camelbodies, nanobodies, and IgNAR, and the antibody fragment is selected from Fab, Fab', and F(ab') fragments.

4. The method of claim 1 , wherein the antibody contains constant regions selected from the group consisting of IgG1, IgG2, IgG3, and IgG4 constant regions.

5. The method of claim 4 , wherein the antibody is an IgG1.

6. The method of claim 5 , wherein the IgG1 comprises a light chain constant region which comprises the amino acid sequence of SEQ NO:586 and a heavy chain constant region which comprises the amino acid sequence of SEQ ID NO:588.

7. The method of claim 1 , wherein the antibody or antibody fragment is aglycosylated.

8. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment is administered to the patient with a frequency of at most once per period of approximately four weeks.

9. The method of claim 1 , wherein the patient's weakness or fatigue remains improved for an entire period intervening two consecutive anti-IL-6 antibody administrations.

10. The method of claim 1 , wherein the anti-IL- 6 antibody or antibody fragment is administered in combination with an antagonist specific to a polypeptide selected from the group consisting of tumor necrosis factor-alpha, Interferon gamma, Interleukin 1 alpha, Interleukin 1 beta, leukernia-inhibitory factor, and any combination thereof.

11. The method of claim 1 , further comprising: measuring the patient's muscular strength prior to administration of the anti-IL-6 antibody or fragment, and administering the anti-IL-6 antibody or antibody fragment after it has been determined that the patient's muscular strength has declined by greater than approximately 20% within approximately 30 days after initially measuring the patient's strength.

12. The method of claim 1 , wherein the patient's weakness is measured by a hand grip strength test before or after antibody administration.

Assignees

• Smith Jeffrey T L
• Schatzman Randall C
• Litton Mark J
• Latham John
• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L
• Schatzman Randall C
• Litton Mark J
• Latham John

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title