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

Patent metadata

Field	Value
Publication number	US-2016102145-A1
Application number	US-201514833973-A
Country	US
Kind code	A1
Filing date	Aug 24, 2015
Priority date	Nov 25, 2008
Publication date	Apr 14, 2016
Grant date	—

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, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, 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

1 - 76 . (canceled)

77 . A method of treating cachexia, weakness, fatigue, and/or fever in a patient diagnosed with an interleukin-6 (IL-6) associated disorder, comprising (1) administering to the patient an anti-IL-6 antibody or antibody fragment comprising a variable light (V L ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:4, 5 and 6, or (ii) and a variable heavy (V H ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:7, 8 or 120 and 9, and (2) detecting cachexia, weakness, fatigue, and/or fever in the patient before, during or after antibody administration.

78 . The method of claim 77 , wherein the anti-IL-6 antibody or antibody fragment comprises an anti-IL-6 antibody or antibody fragment comprising a variable light (V L ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:4, 5 and 6, or (ii) and a variable heavy (V H ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:7, 120 and 9.

79 . The method of claim 77 , wherein the anti-IL-6 antibody or antibody fragment comprises an anti-IL-6 antibody or antibody fragment comprising a variable light (V L ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:4, 5 and 6, or (ii) and a variable heavy (V H ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:7, 8 and 9.

80 . The method of claim 77 , wherein the anti-IL-6 antibody or antibody fragment comprises a human IgG1 constant region.

81 . The method of claim 78 , wherein the anti-IL-6 antibody or antibody fragment comprises a human IgG1 constant region.

82 . The method of claim 79 , wherein the anti-IL-6 antibody or antibody fragment comprises a human IgG1 constant region.

83 . The method of claim 77 , further comprising administering an antagonist of a cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor other than an anti-IL-6 antibody or antibody fragment.

84 . The method of claim 83 , wherein the cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor is selected from tumor necrosis factor-alpha, Interferon gamma, Interleukin 1 alpha, Interleukin 1 beta, Interleukin 6, proteolysis inducing factor, leukemia-inhibitory factor, or any combination thereof.

85 . The method of claim 77 , 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.

86 . The method of claim 77 , wherein the anti-IL-6 antibody comprises the constant regions having the amino acid sequences of SEQ ID NO:588 and 586

87 . The method of claim 78 , wherein the anti-IL-6 antibody comprises the constant regions having the amino acid sequences of SEQ ID NO:588 and 586.

88 . The method of claim 79 , wherein the anti-IL-6 antibody comprises the constant regions having the amino acid sequences of SEQ ID NO:588 and 586.

89 . The method of claim 77 , wherein detecting cachexia, weakness, fatigue, and/or fever in the patient is effected before anti-IL-6 antibody administration.

90 . The method of claim 77 , wherein detecting cachexia, weakness, fatigue, and/or fever in the patient is effected after anti-IL-6 antibody administration.

91 . The method of claim 77 , wherein detecting cachexia, weakness, fatigue, and/or fever in the patient is effected before and after anti-IL-6 antibody administration.

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L
• Latham John A
• Litton Mark
• Schatzman Randall

Classifications

• C07K2317/92

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

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07K16/248 Primary

  IL-6 · CPC title