Methods and compositions for use in treatment of patients with autoantibody positive disease

• US 9,168,286 B2
• Filed: 06/06/2008
• Issued: 10/27/2015
• Est. Priority Date: 10/13/2005
• Status: Active Grant

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Chevrier, Marc, Freimuth, William W., Zhong, Zhenshao, Odenheimer, Daniel
• Primary Examiner(s): Kolker, Daniel E
• Assistant Examiner(s): MACFARLANE, STACEY NEE
• Application Number:
  US12/135,025
• Publication Number:
  US 20090148462A1
• Time in Patent Office: 2,699 Days
• Field of Search: None
• US Class Current: 1/1
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/19 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• 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 16/2887 against CD20
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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 method of reducing the frequency or quantity of corticosteroid administered to a patient with systemic lupus erythematosus comprising:

(a) providing a patient that has systemic lupus erythematosus and to whom a corticosteroid is being administered at a first frequency or quantity;

(b) administering a therapeutically effective amount of an antagonist of Neutrokine-alpha to said patient, wherein the antagonist of Neutrokine-alpha is

an anti-Neutrokine-alpha antibody;

and

(c) administering the corticosteroid to said patient at a second frequency or quantity that is less than the first frequency or quantity.

2. The method of claim 1 wherein the antagonist of Neutrokine-alpha is only administered when the patient has at least one characteristic selected from the group consisting of:

(a) an ANA titer ≧

1;

80;

(b) ≧

30 IU/mL of anti-dsDNA antibodies in his/her blood plasma or serum;

(c) a SELENA SLEDAI score ≧

6;

(d) a depressed level of C3 complement factor in his/her blood plasma or serum;

(e) a depressed level of C4 complement factor in his/her blood plasma or serum;

(f) the patient is receiving ≧

7.5 milligrams/day of prednisone; and

(g) the patient is receiving or had previously received immunosuppressant therapy for the treatment of lupus-related symptoms.

3. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient has ≧

30 IU/mL of anti-dsDNA antibodies in his/her blood plasma or serum.

4. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient has an ANA titer ≧

1;

80 and ≧

30 IU/mL of anti-dsDNA antibodies in his/her blood plasma or serum.

5. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient has a SELENA SLEDAI score ≧

6.

6. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient has less than 90 milligrams/deciliter of C3 complement factor in his/her blood plasma or serum.

7. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient has less than 16 milligrams/deciliter of C4 complement factor in his/her blood plasma or serum.

8. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient is receiving ≧

7.5 milligrams/day of prednisone.

9. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient is receiving or had previously received immunosuppressant therapy for the treatment of lupus-related symptoms.

10. The method of claim 2 wherein the antagonist of Neutrokine-alpha is only administered when the patient has an ANA titer ≧

1;

80.

11. The method of claim 1 wherein the corticosteroid is selected from the group consisting of prednisone, prednisolone, hydrocortisone, methylprednisolone and dexamethasone.

12. The method of claim 1 wherein the corticosteroid is prednisone.

13. The method of claim 12 wherein the quantity of prednisone administered to the patient is reduced by at least 25% to ≦

7.5 milligrams/day following administration of the antagonist of Neutrokine-alpha.

14. The method of claim 1 wherein the antibody comprises the amino acid sequences of a set of VH and VL domains selected from the group consisting of:

(a) the VH domain and the VL domain of SEQ ID NO;

13;

(b) the VH domain and the VL domain of SEQ ID NO;

14;

(c) the VH domain and the VL domain of SEQ ID NO;

15;

(d) the VH domain and the VL domain of SEQ ID NO;

16;

(e) the VH domain and the VL domain of SEQ ID NO;

17;

(f) the VH domain and the VL domain of SEQ ID NO;

18;

(g) the VH domain of SEQ ID NO;

19 and the VL domain of SEQ ID NO;

20; and

(h) the VH domain of SEQ ID NO;

21 and the VL domain of SEQ ID NO;

22.

15. The method of claim 1 wherein the antibody comprises the amino acid sequences of the VH domain and the VL domain of SEQ ID NO:

17.