METHODS AND COMPOSITIONS FOR USE IN TREATMENT OF PATIENTS WITH AUTOANTIBODY POSITIVE DISEASE

• US 20090081213A1
• Filed: 08/05/2008
• Published: 03/26/2009
• Est. Priority Date: 10/13/2005
• Status: Abandoned Application

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: CHEVRIER, MARC, Perkins, Melissa D., Zhong, Zhenshao, Odenheimer, Daniel, Freimuth, William W.
• Application Number:
  US12/186,404
• Publication Number:
  US 20090081213A1
• Time in Patent Office: Days
• US Class Current: 424/133.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The present invention relates to methods and compositions for use in treatment of patients with autoantibody positive disease. In a specific embodiment, the present invention relates to a method of treating a patient that has an ANA titer of 1:80 or greater and/or greater than or equal to 30 IU/ml of anti-dsDNA antibodies in his/her blood plasma or serum comprising administering a therapeutically effective amount of an immunomodulatory agent, such as an antagonist of Neutrokine-alpha. Additionally provided is a method of reducing the frequency and/or quantity of corticosteroid administration to patients. In preferred embodiments, the patient has systemic lupus erythematosus. Methods for determining if a lupus patient is responding to medical treatment are also provided.

Claims

1. A formulation comprising a Neutrokine a antibody, a buffer in an amount from about 51 nM to about 50 mM, NaCl in an amount from about 150 mM to about 500 mM, a surfactant in an amount from about 0.003% to about 0.05%, and water, with a pH from about 5.5 to about 6.5.

2. The formulation of claim 1 wherein, the buffer is 10 mM histidine, the surfactant is polysorbate 80 in an amount of 0.01% w/v, the NaCl is 150 mM and wherein the formulation has a pH of 6.0.

3. The formulation of claim 2 which is stable at a temperature of about 2-8°

C. for at least one or two year(s).

4. The formulation of claim 2 wherein the Neutrokine a antibody is selected from the group consisting of:

(a) a whole immunoglobulin molecule;

(b) an scFv;

(c) a monoclonal antibody;

(d) a human antibody;

(e) a chimeric antibody;

(f) a humanized antibody;

(g) a Fab fragment;

(h) an Fab′

fragment;

(i) an F (ab′

) 2;

(j) an Fv; and

(k) a disulfide linked Fv.

5. The formulation of claim 2 wherein the Neutrokine a antibody is present in an amount of 100 mg/mL.

6. The formulation of claim 1 comprising 100 mg/mL Neutrokine a antibody, 0.74 mg/mL L-histidine, 1.1 mg/mL L-histidine monohydrocholoride, 8.8 mg/mL NaCl and 0.1 mg/mL polysorbate 80 and wherein the formulation has a pH of 6.0.

7. The formulation of claim 1 wherein the Neutrokine a antibody comprises a sequence having at least 85% identity to amino acid residues 1-123 and 141-249 of SEQ ID NO:

17.

8. The formulation of claim 1 wherein the Neutrokine a antibody comprises amino acid residues 1-123 and 141-249 of SEQ ID NO:

17.

9. The formulation of claim 8 wherein the buffer is 10 mM histidine, the surfactant is polysorbate 80 in an amount of 0.01% w/v, the NaCl is 1501 nM and wherein the formulation has a pH of 6.0.

10. The formulation of claim 9 which is stable at a temperature of about 2-8°

C. for at least one or two year(s).

11. The formulation of claim 9, wherein the Neutrokine a antibody is selected from the group consisting of:

(a) a whole immunoglobulin molecule;

(b) an scFv;

(c) a monoclonal antibody;

(d) a human antibody;

(e) a chimeric antibody;

(f) a humanized antibody;

(g) a Fab fragment;

(h) an Fab′

fragment;

(i) an F (ab′

) 2;

(j) an Fv; and

(k) a disulfide linked Fv.

12. The formulation of claim 9 wherein the antibody is present in an amount of 100 mg/mL.

13. The formulation of claim 8 comprising 100 mg/mL Neutrokine a antibody, 0.74 mg/mL L-histidine, 1.1 mg/mL L-histidine monohydrocholoride, 8.8 mg/mL NaCl and 0.1 mg/mL polysorbate 80 and wherein the formulation has a pH of 6.0.

14. The formulation of claim 12 wherein the Neutrokine-alpha antibody further comprises a human IgG1 heavy chain immunoglobulin constant domain and a human lambda light chain immunoglobulin constant domain.

15. The formulation of claim 13 wherein the Neutrokine-alpha antibody further comprises a human IgG1 heavy chain immunoglobulin constant domain and a human lambda light chain immunoglobulin constant domain

16. A formulation comprising a Neutrokine a antibody, 10 mM sodium citrate, 1.9% glycine, 0.5% sucrose, 0.01% w/v polysorbate 80, with a pH from about 6.2 to about 6.8.

17. The formulation of claim 16 wherein the Neutrokine a antibody comprises a sequence having at least 85% identity to amino acid residues 1-123 and 141-249 of SEQ ID NO:

17.

18. A formulation comprising a Neutrokine a antibody, 10 mM sodium citrate, 8% sucrose, 0.04% w/v polysorbate 80 with a pH from about 6.2 to about 6.8.

19. The formulation of claim 18 wherein the Neutrokine a antibody comprises a sequence having at least 85% identity to amino acid residues 1-123 and 141-249 of SEQ ID NO:

17.

20. The formulation of claim 18 wherein the Neutrokine a antibody comprises amino acid residues 1-123 and 141-249 of SEQ ID NO:

17.