You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 28, 2024

Claims for Patent: 9,290,574


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 9,290,574
Title:Methods for treating eosinophilic esophagitis by administering an IL-4R inhibitor
Abstract: The present invention provides methods for treating, preventing or reducing the severity of eosinophilic esophagitis. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R.alpha.) inhibitor such as an anti-IL-4R.alpha. antibody.
Inventor(s): Kostic; Ana (New York, NY), Kelly; Ludmila (Tarrytown, NY), Liu; Xia (Hopewell Junction, NY), Classon; Brendan J. (Seattle, WA)
Assignee: Regeneron Pharmaceuticals, Inc. (Tarrytown, NY)
Application Number:14/328,336
Patent Claims:1. A method of treating or ameliorating at least one symptom or indication of eosinophilic esophagitis (EoE) comprising administering a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) inhibitor to a subject in need thereof.

2. The method of claim 1, wherein the symptom or indication of EoE is selected from the group consisting of eosinophilic infiltration of the esophagus, thickening of the esophageal wall, food refusal, vomiting, abdominal pain, heartburn, regurgitation, dysphagia and food impaction.

3. The method of claim 1, wherein the subject exhibits an allergic reaction to a food allergen contained in a food item selected from the group consisting of a dairy product, egg, wheat, soy, corn, fish, shellfish, peanut, a tree nut, beef, chicken, oat, barley, pork, green beans, apple and pineapple.

4. The method of claim 1, wherein the subject exhibits an allergic reaction to a non-food allergen derived from one of dust, pollen, mold, plant, cat, dog or insect.

5. The method of claim 1, wherein the administration of the IL-4R inhibitor results in reducing the level of an EoE-associated biomarker in the subject.

6. The method of claim 5, wherein the EoE-associated biomarker is selected from the group consisting of esophagus eosinophils, eotaxin-3, periostin, serum IgE (total and allergen-specific), IL-13, IL-5, serum thymus and activation regulated chemokine (TARC), thymic stromal lymphopoietin (TSLP), serum eosinophilic cationic protein (ECP), and eosinophil-derived neurotoxin (EDN).

7. The method of claim 1, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that binds IL-4R.alpha. and prevents the interaction of IL-4 and/or IL-13 with a type 1 or type 2 IL-4 receptor.

8. The method of claim 7, wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 and IL-13 with both type 1 and type 2 IL-4 receptors.

9. The method of claim 8, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and the light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

10. The method of claim 9, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; LCDR1 comprises the amino acid sequence of SEQ ID NO: 6; LCDR2 comprises the amino acid sequence of SEQ ID NO: 7; and LCDR3 comprises the amino acid sequence of SEQ ID NO: 8.

11. The method of claim 10, wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1 and the LCVR comprises the amino acid sequence of SEQ ID NO: 2.

12. The method of claim 8, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 13 and a light chain comprising the amino acid sequence of SEQ ID NO: 14.

13. The method of claim 1, wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof.

14. The method of claim 1, wherein the IL-4R inhibitor is administered in combination with a second therapeutic agent or therapy, wherein the second therapeutic agent or therapy is selected from the group consisting of an IL-1beta inhibitor, an IL-5 inhibitor, an IL-9 inhibitor, an IL-13 inhibitor, an IL-17 inhibitor, an IL-25 inhibitor, a TNFalpha inhibitor, an eotaxin-3 inhibitor, an IgE inhibitor, a prostaglandin D2 inhibitor, an immunosuppressant, a corticosteroid, a glucocorticoid, a proton pump inhibitor, a non-steroidal anti-inflammatory drug (NSAID), allergen removal and diet management.

15. The method of claim 1, wherein the subject, prior to or at the time of administration of the IL-4R inhibitor, has or is diagnosed with a disease or disorder selected from the group consisting of atopic dermatitis, asthma, allergic rhinitis and allergic conjunctivitis.

16. A method of treating or ameliorating at least one symptom or indication of eosinophilic esophagitis (EoE) comprising: (a) selecting a subject having an allergic reaction to an allergen that renders the subject susceptible to EoE; and (b) administering a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) inhibitor to the subject in need thereof.

17. The method of claim 16, wherein the allergen is a food allergen contained in a food item selected from the group consisting of a dairy product, egg, wheat, soy, corn, fish, shellfish, peanut, a tree nut, beef, chicken, oat, barley, pork, green beans, apple and pineapple.

18. The method of claim 16, wherein the allergen is a non-food allergen derived from one of dust, pollen, mold, plant, cat, dog or insect.

19. The method of claim 16, wherein the symptom or indication of EoE is selected from the group consisting of eosinophilic infiltration of the esophagus, thickening of the esophageal wall, food refusal, vomiting, abdominal pain, heartburn, regurgitation, dysphagia and food impaction.

20. The method of claim 16, wherein the administration of the IL-4R inhibitor results in reducing the level of an EoE-associated biomarker in the subject.

21. The method of claim 20, wherein the EoE-associated biomarker is selected from the group consisting of esophagus eosinophils, eotaxin-3, IgE, TARC, periostin, IL-5, IL-13, thymic stromal lymphopoietin (TSLP), and eosinophil-derived neurotoxin (EDN).

22. The method of claim 16, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that binds IL-4R.alpha. and prevents the interaction of IL-4 and/or IL-13 with a type 1 or type 2 IL-4 receptor.

23. The method of claim 22, wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 and IL-13 with both type 1 and type 2 IL-4 receptors.

24. The method of claim 23, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and the light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

25. The method of claim 24, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; LCDR1 comprises the amino acid sequence of SEQ ID NO: 6; LCDR2 comprises the amino acid sequence of SEQ ID NO: 7; and LCDR3 comprises the amino acid sequence of SEQ ID NO: 8.

26. The method of claim 25, wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1 and the LCVR comprises the amino acid sequence of SEQ ID NO: 2.

27. The method of claim 23, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 13 and a light chain comprising the amino acid sequence of SEQ ID NO: 14.

28. The method of claim 16, wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof.

29. The method of claim 16, wherein the IL-4R inhibitor is administered in combination with a second therapeutic agent or therapy, wherein the second therapeutic agent or therapy is selected from the group consisting of an IL-1 beta inhibitor, an IL-5inhibitor, an IL-9 inhibitor, an IL-13 inhibitor, an IL-17 inhibitor, an IL-25 inhibitor, a TNFalpha inhibitor, an eotaxin-3 inhibitor, an IgE inhibitor, a prostaglandin D2 inhibitor, an immunosuppressant, a corticosteroid, a glucocorticoid, a proton pump inhibitor, a non-steroidal anti-inflammatory drug (NSAID), allergen removal and diet management.

30. The method of claim 16, wherein the subject, prior to or at the time of administration of the IL-4R inhibitor, has or is diagnosed with a disease or disorder selected from the group consisting of atopic dermatitis, asthma, allergic rhinitis and allergic conjunctivitis.

31. A method of treating or ameliorating at least one symptom or indication of eosinophilic esophagitis (EoE) comprising: (a) selecting a subject who exhibits at least one symptom or indication of EoE, wherein the subject has an elevated level of a biomarker selected from the group consisting of esophagus eosinophils, eotaxin-3, periostin, serum IgE (total and allergen-specific), IL-13, IL-5, TARC, TSLP, serum ECP, and EDN; and (b) administering a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) inhibitor to the subject in need thereof.

32. The method of claim 31, wherein the subject is selected on the basis of exhibiting .gtoreq.15 eosinophils per high powered field (hpf) in the esophagus prior to or at the time of the treatment ("baseline").

33. The method of claim 32, wherein the subject exhibits at least 50% decrease in the number of eosinophils per hpf from baseline at day 10 following the administration of the IL-4R inhibitor.

34. The method of claim 31, wherein the subject is selected on the basis of exhibiting an eotaxin-3 level of greater than about 50 pg/mL prior to or at the time of initiation of treatment ("baseline").

35. The method of claim 34, wherein the subject exhibits at least 50% decrease in eotaxin-3 level from baseline at day 10 following the administration.

36. The method of claim 31, wherein the subject exhibits an allergic reaction to a food allergen is contained in a food item selected from the group consisting of a dairy product, egg, wheat, soy, corn, fish, shellfish, peanut, a tree nut, beef, chicken, oat, barley, pork, green beans, apple and pineapple.

37. The method of claim 31, wherein the subject exhibits an allergic reaction to a non-food allergen derived from a source selected from the group consisting of dust, pollen, mold, plant, cat, dog and insect.

38. The method of claim 31, wherein the indication is selected from the group consisting of eosinophilic infiltration of the esophagus, thickening of the esophageal wall, food refusal, vomiting, abdominal pain, heartburn, regurgitation, dysphagia and food impaction.

39. The method of claim 31, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that binds IL-4R.alpha. and prevents the interaction of IL-4 and/or IL-13 with a type 1 or type 2 IL-4 receptor.

40. The method of claim 39, wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 and IL-13 with both type 1 and type 2 IL-4receptors.

41. The method of claim 40, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain complementarity determining regions (HCDRs) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and the light chain complementarity determining regions (LCDRs) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

42. The method of claim 41, wherein the antibody or antigen-binding fragment thereof comprises three HCDRs (HCDR1, HCDR2 and HCDR3) and three LCDRs (LCDR1, LCDR2 and LCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 7; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 8.

43. The method of claim 42, wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1 and the LCVR comprises the amino acid sequence of SEQ ID NO: 2.

44. The method of claim 40, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 13 and a light chain comprising the amino acid sequence of SEQ ID NO: 14.

45. The method of claim 31, wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof.

46. The method of claim 31, wherein the IL-4R inhibitor is administered in combination with a second therapeutic agent or therapy, wherein the second therapeutic agent or therapy is selected from the group consisting of an IL-1 beta inhibitor, an IL-5 inhibitor, an IL-9inhibitor, an IL-13 inhibitor, an IL-17 inhibitor, an IL-25 inhibitor, a TNFalpha inhibitor, an eotaxin-3 inhibitor, an IgE inhibitor, a prostaglandin D2 inhibitor, an immunosuppressant, a corticosteroid, a glucocorticoid, a proton pump inhibitor, a NSAID, allergen removal and diet management.

Details for Patent 9,290,574

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Aimmune Therapeutics, Inc. PALFORZIA peanut (arachis hypogaea) allergen powder Powder 125696 01/31/2020 ⤷  Try a Trial 2033-07-11
Regeneron Pharmaceuticals, Inc. DUPIXENT dupilumab Injection 761055 03/28/2017 ⤷  Try a Trial 2033-07-11
Regeneron Pharmaceuticals, Inc. DUPIXENT dupilumab Injection 761055 10/19/2018 ⤷  Try a Trial 2033-07-11
Regeneron Pharmaceuticals, Inc. DUPIXENT dupilumab Injection 761055 06/18/2020 ⤷  Try a Trial 2033-07-11
Regeneron Pharmaceuticals, Inc. DUPIXENT dupilumab Injection 761055 06/14/2021 ⤷  Try a Trial 2033-07-11
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.