Methods of reducing CRP and/or increasing serum albumin in patients in need using IL-6 antibodies of defined epitopic specificity

1. A method of improving survivability or quality of life of a patient in need thereof having elevated C-reactive protein levels, comprising administering to the patient an anti-interleukin-6 (“IL-6”), antibody or anti-IL-6 antibody fragment, wherein the antibody or antibody fragment specifically binds to an epitope on an intact human IL-6 polypeptide, wherein said epitope, when ascertained by epitopic mapping using overlapping linear peptide fragments which span the full length of the native human IL-6 polypeptide, includes one or more residues comprised in each of the human IL-6 fragments selected from those respectively consisting of (a) amino acid residues 37-51, (b) amino acid residues 70-84, (c) amino acid residues 169-183, (d) amino acid residues 31-45 and (e) amino acid residues 58-72 of the human IL-6 polypeptide having the sequence in SEQ ID NO:1, and whereby the patient's serum C-reactive protein (“CRP”) is reduced, and further whereby the administration of the anti-IL-6 antibody or antibody fragment results in improved survivability and/or quality of life of said patient.

2. A method of improving survivability or quality of life of a patient in need thereof having reduced serum albumin levels, comprising administering to the patient an anti-interleukin-6 (“IL-6”) antibody or antibody fragment, wherein the antibody or antibody fragment specifically binds to an epitope on an intact human IL-6 polypeptide, wherein said epitope, when ascertained by epitopic mapping using overlapping linear peptide fragments which span the full length of the native human IL-6 polypeptide, includes one or more residues comprised in each of the human IL-6 fragments selected from those respectively consisting of (a) amino acid residues 37-51, (b) amino acid residues 70-84, (c) amino acid residues 169-183, (d) amino acid residues 31-45 and (e) amino acid residues 58-72 of the human IL-6 polypeptide having the sequence in SEQ ID NO:1, whereby the patient's serum albumin level is increased, and further whereby the administration of the anti-IL-6 antibody or antibody fragment results in improved survivability and/or quality of life of said patient.

3. A method of improving survivability or quality of life of a patient in need thereof having increased C reactive protein and reduced serum albumin levels, comprising administering to the patient an anti-interleukin-6 (“IL-6”) antibody or antibody fragment, wherein the antibody or antibody fragment specifically binds to an epitope on an intact human IL-6 polypeptide, wherein said epitope, when ascertained by epitopic mapping using overlapping linear peptide fragments which span the full length of the native human IL-6 polypeptide, includes one or more residues comprised in each of the human IL-6 fragments selected from those respectively consisting of (a) amino acid residues 37-51, (b) amino acid residues 70-84, (c) amino acid residues 169-183, (d) amino acid residues 31-45 and (e) amino acid residues 58-72 of the human IL-6 polypeptide having the sequence in SEQ ID NO:1, and whereby this administration results in the reduction of the patient's serum C-reactive protein (“CRP”) level and the increase in the patient's serum albumin level, and further whereby the administration of the anti-IL-6 antibody or antibody fragment results in improved survivability and/or quality of life of said patient.

4. The method of any one of claims 1 - 3 , wherein before or after the administration of said anti-IL-6 antibody or fragment either or both serum albumin and C-reactive protein levels are determined.

5. The method of any one of claims 1 - 3 , wherein after the administration of said anti-IL-6 antibody or fragment either or both serum albumin and C-reactive protein levels are monitored.

6. The method of any one of claims 1 - 3 , wherein said patient has an elevated serum C-reactive protein (“CRP”) level or reduced serum albumin level prior to treatment.

7. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody is an anti-IL-6 antibody fragment.

8. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody is an intact anti-IL-6 antibody.

9. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or antibody fragment is administered to the patient with a frequency at most once per period of approximately four weeks.

10. The method of any one of claims 1 - 3 , wherein the patient's serum C-reactive protein (“CRP”) level remains decreased and/or serum albumin level remains raised for an entire period intervening two consecutive anti-IL-6 antibody or antibody fragment administrations.

11. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or antibody fragment has an elimination half-life of at least about 22 days.

12. The method of claim 1 or 3 , further comprising: measuring the patient's serum C-reactive protein (“CRP”) level prior to administration of the anti-IL-6 antibody or antibody fragment, and administering the anti-IL-6 antibody or antibody fragment if the patient's serum CRP level is at least approximately 5 mg/L.

13. The method of claim 12 , wherein the patient's serum C-reactive protein (“CRP”) level is reduced to less than approximately 5 mg/L within 1 week of administration of the anti-IL-6 antibody or antibody fragment.

14. The method of claim 1 or 3 , wherein the patient's serum C-reactive protein (“CRP”) level is reduced to below 10 mg/L within about 1 week of the anti-IL-6 antibody or antibody fragment administration.

15. The method of claim 1 or 3 , further comprising: measuring the patient's serum albumin level prior to administration of the anti-IL-6 antibody or antibody fragment, and administering the anti-IL-6 antibody or antibody fragment , and administering the IL-6 antibody if the patient's serum albumin level is less than approximately 35 g/L.

16. The method of claim 15 , wherein the patient's serum albumin level is increased to more than approximately 35 g/L within about 5 weeks of administration of the anti-IL-6 antibody or antibody fragment.

17. The method of any one of claims 1 - 3 , further comprising administration of one or more statins to the patient.

18. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or fragment is aglycosylated.

19. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or fragment comprises a human constant domain.

20. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or fragment comprises a human gamma 1 constant domain.

21. The method of any one of claims 1 - 3 , wherein said antibody is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.

22. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or fragment is administered intravenously, intraperitoneally, intramuscularly, or subcutaneously.

23. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or antibody fragment contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.

24. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or antibody fragment is a human, humanized, single chain or chimeric antibody.

25. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or antibody fragment is aglycosylated.

26. The method of any one of claims 1 - 3 , wherein the anti-IL-6 antibody or antibody fragment substantially neutralizes IL-6 in vivo and inhibits the interaction of human IL-6 with both gp 130 and IL-6R.

27. The method of any one of claims 1 - 3 , wherein the serum albumin levels in the patient remain elevated and/or the CRP levels remain decreased after antibody administration has been discontinued for at least 14 days.

28. The method of any one of claims 1 - 3 , wherein the serum albumin level in the patient remains elevated and/or the CRP level remains decreased after antibody administration has been discontinued for at least 21 days.