Modulation of immunoglobulin production and atopic disorders

• US 20060024268A1
• Filed: 05/19/2005
• Published: 02/02/2006
• Est. Priority Date: 05/19/2004
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Collins, Mary, Donaldson, Debra D., Kasaian, Marion T., Wood, Nancy L.
• Application Number:
  US11/132,947
• Publication Number:
  US 20060024268A1
• Time in Patent Office: Days
• US Class Current: 424/85.200
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2800/20 Dermatological disorders
• CPC Class Codes: G01N 2800/24 Immunology or allergic disorders
• CPC Class Codes: G01N 33/6854 Immunoglobulins
• CPC Class Codes: G01N 33/6869 Interleukin

Abstract

An IL-21 polypeptide or other IL-21 pathway agonist can be used to treat atopic disorders, e.g., asthma.

Claims

1. A method of ameliorating a symptom of an atopic disorder in a human subject, the method comprising:

administering, to the subject, a human IL-21 polypeptide that comprises the amino acid sequence of SEQ ID NO;

2, in an amount effective for ameliorating at least one symptom of the atopic disorder.

2. The method of claim 1 wherein the atopic disorder is selected from the group consisting of:

atopic dermatitis, asthma, extrinsic bronchial asthma, urticaria, eczema, allergic rhinitis, and allergic enterogastritis.

3. The method of claim 1 wherein IgE levels are decreased by at least 40% relative to levels in the subject prior to the administering.

4. The method of claim 1 further comprising evaluating one or more symptoms of the atopic disorder in the subject.

5. The method of claim 1 further comprising evaluating an IL-21 associated parameter in the subject.

6. The method of claim 1 further comprising evaluating levels of endogenous IgE in the subject.

7. A method of treating or preventing an atopic disorder in a human subject, the method comprising:

administering, to the subject, a human IL-21 polypeptide that comprises the amino acid sequence of SEQ ID NO;

2, in an amount effective for treating or preventing the atopic disorder.

8. The method of claim 7 wherein the atopic disorder is selected from the group consisting of:

atopic dermatitis, asthma, extrinsic bronchial asthma, urticaria, eczema, allergic rhinitis, and allergic enterogastritis.

9. A method of modulating IgG and/or IgE production in a cell, the method comprising:

contacting an IL-21 pathway agonist that is an IL-21 polypeptide or a nucleic acid encoding an IL-21 polypeptide, to the cell in an amount sufficient to increase IgG production and/or decrease IgE production.

10. The method of claim 9 wherein the IL-21 pathway agonist is an IL-21 polypeptide.

11. The method of claim 9 wherein IgE levels are decreased by at least 40%.

12. The method of claim 9 wherein the cell is in vitro.

13. The method of claim 9 wherein the cell is in vivo.

14. The method of claim 9 wherein IgE/IgG ratio is decreased.

15. A method of modulating IgG and/or IgE production in a cell, the method comprising:

contacting an IL-21 pathway antagonist, to the cell in an amount sufficient to decrease IgG and/or increase IgE production, wherein the antagonist is selected from the group consisting of;

(i) an antibody that binds IL-21, (ii) a polypeptide that comprises a soluble form of the IL-21 receptor, or (iii) a nucleic acid that reduces expression of IL-21, IL-21 receptor, or an IL-21 pathway component.

16. The method of claim 15 wherein IgE levels are increased by at least 20%.

17. The method of claim 15 wherein IgE/IgG ratio is increased.

18. The method of claim 17 wherein the ratio is increased by at least 20%.

19. A pharmaceutical composition comprising a human IL-21 polypeptide and a second agent for treating an atopic disorder.

20. A method of evaluating a subject having or suspected of having an atopic disorder, the method comprising

evaluating an IL-21 associated parameter for a subject having an atopic disorder

comparing results of the evaluating to a reference parameter, and

providing a recommendation of a therapy for the disorder as a function of the comparison.

21. The method of claim 20 wherein the IL-21 associated parameter comprises a quantitative or qualitative value for IL-21 polypeptide abundance or IL-21 mRNA.

22. The method of claim 20 wherein the IL-21 associated parameter comprises a quantitative or qualitative value for IL-21 receptor protein or mRNA, or for an IL-21 pathway activity.

23. The method of claim 20 wherein the atopic disorder is selected from the group consisting of:

atopic dermatitis, asthma, extrinsic bronchial asthma, urticaria, eczema, allergic rhinitis, and allergic enterogastritis.