Claims for Patent: 10,485,844

Summary for Patent: 10,485,844

Title:	Methods for treating severe atopic dermatitis by administering an IL-4R inhibitor
Abstract:	The present invention provides methods for treating moderate-to-severe or severe atopic dermatitis (AD). The methods of the present invention comprise administering to a subject in need thereof one or more doses of an interleukin-4 receptor (IL-4R) inhibitor such as an anti-IL-4R antibody. In certain embodiments, the methods of the present invention are used to treat severe AD in a patient whose disease is not controlled with systemic therapy (e.g., cyclosporine A) or when such therapy is inadvisable.
Inventor(s):	Radin; Allen (New York, NY), Graham; Neil (Croton-on-Hudson, NY), Akinlade; Bolanle (White Plains, NY), Pirozzi; Gianluca (Bridgewater, NJ), Sun; Xing (Bridgewater, NJ), Hultsch; Thomas (Bridgewater, NJ), Shumel; Brad S. (Chappaqua, NY), Bansal; Ashish (White Plains, NY)
Assignee:	Regeneron Pharmaceuticals, Inc. (Tarrytown, NY) Sanofi Biotechnology (Paris, FR)
Application Number:	15/711,815
Patent Claims:	1. A method of reducing pruritus or improving at least one atopic dermatitis (AD)-associated parameter comprising: (a) selecting a patient with AD, wherein the patient has a history of inadequate response or intolerance to a systemic immunosuppressant and/or wherein therapy with a systemic immunosuppressant is inadvisable; and (b) administering a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) inhibitor in combination with a topical corticosteroid (TCS) to the patient in need thereof, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that specifically binds IL-4R, 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. 2. The method of claim 1, wherein the patient has one or more characteristics selected from the group consisting of: (i) the patient has a baseline Investigator's Global Assessment (IGA) score=4; (ii) the patient has a baseline IGA score .gtoreq.3; (iii) the patient is a candidate for systemic therapy; (iv) the patient has disease that is uncontrolled by topical AD therapy; (v) the patient has a documented history of inadequate response to topical AD therapy or for whom topical therapy is inadvisable due to adverse side effects or safety risks; (vi) the patient has been previously treated with a medication or procedure selected from the group consisting of a topical corticosteroid, a topical calcineurin inhibitor, an anti-histamine, an emollient, a dermatological therapeutic, a systemic glucocorticoid, a non-steroidal systemic immunosuppressant, cyclosporine A, azathioprine, ultraviolet (UV) light therapy, and phototherapy; and (vii) the patient, 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 food allergy, asthma, seasonal allergy, allergic rhinitis, house dust allergy, and allergic conjunctivitis. 3. The method of claim 1, wherein the systemic immunosuppressant is selected from the group consisting of cyclosporine A (CSA), methotrexate, mycophenolate mofetil, azathioprine, systemic corticosteroids, and interferon-gamma. 4. The method of claim 3, wherein the systemic immunosuppressant is CSA. 5. The method of claim 4, wherein the patient has no prior exposure to CSA, and CSA therapy is inadvisable due to a condition selected from the group consisting of medical contraindications, hypersensitivity to CSA or excipients, use of a concomitant medication prohibited with CSA, increased susceptibility to CSA-induced renal damage, increased susceptibility to CSA-induced liver damage, and increased risk of serious infections. 6. The method of claim 4, wherein the patient is previously exposed to CSA, and CSA therapy is inadvisable due to a condition selected from the group consisting of intolerance, unacceptable toxicity, inadequate response, requirement for CSA at a dose >5 mg/kg/day of the patient's body weight, and requirement of CSA administration for a duration >1 year. 7. The method of claim 1, wherein the IL-4R inhibitor is administered at a dose of about 50-about 600 mg. 8. The method of claim 7, wherein the IL-4R inhibitor is administered at a dose of about 300 mg. 9. The method of claim 1, wherein the IL-4R inhibitor is administered at an initial dose followed by one or more secondary doses, wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose. 10. The method of claim 9, wherein the initial dose comprises about 50-about 600 mg of the IL-4R inhibitor. 11. The method of claim 10, wherein each secondary dose comprises about 25-about 400 mg of the IL-4R inhibitor. 12. The method of claim 9, wherein the initial dose comprises about 600 mg of the IL-4R inhibitor, and each secondary dose comprises about 300 mg of the IL-4R inhibitor. 13. The method of claim 12, wherein each secondary dose is administered one week after the immediately preceding dose. 14. The method of claim 12, wherein each secondary dose is administered 2 weeks after the immediately preceding dose. 15. The method of claim 1, wherein administration of the IL-4R inhibitor results in improvement of an AD-associated parameter selected from the group consisting of: (a) a decrease from baseline in Eczema Area and Severity Index (EAST) score of at least 75%; (b) a decrease from baseline in Pruritus Numeric Rating Scale (NRS) score of at least 45%; (c) a decrease from baseline in Scoring Atopic Dermatitis (SCORAD) score of at least 50%; (d) a decrease from baseline in Investigator's Global Assessment (IGA) score of .gtoreq.2 points; and (e) a decrease from baseline in NRS score of .gtoreq.3 points. 16. The method of claim 1, wherein administration of the IL-4R inhibitor results in an improvement in at least one patient-related outcome selected from the group consisting of Global Individual Signs Score (GISS), Patient Oriented Eczema Measure (POEM), Patient-assessed Hospital Anxiety and Depression Scale (HADS), and Patient-reported Dermatology Life Quality Index (DLQI). 17. The method of claim 1, wherein administration of the IL-4R inhibitor results in a decrease in the number of flares or exacerbations in the patient. 18. The method of claim 1, wherein the IL-4R inhibitor is administered subcutaneously. 19. The method of claim 1, wherein the IL-4R inhibitor is administered in combination with an additional therapeutic agent or therapy, wherein the second therapeutic agent or therapy is selected from the group consisting of calcineurin inhibitors and emollients. 20. The method of claim 1, wherein the TCS is selected from the group consisting of low-potency TCS, medium-potency TCS, and high-potency TCS. 21. The method of claim 20, wherein the amount of TCS administered to the patient is gradually reduced following administration of the first dose of the IL-4R inhibitor. 22. The method of claim 21, wherein the amount of TCS administered to the patient is reduced by least about 20% by 4 weeks following administration of the first dose of the IL-4R inhibitor. 23. The method of claim 21, wherein the amount of TCS administered to the patient is reduced by about 50% by 4 weeks following administration of the first dose of the IL-4R inhibitor. 24. The method of claim 1, wherein the antibody or antigen-binding fragment prevents the interaction of IL-4 and/or IL-13 with a type 1 or type 2 IL-4 receptor. 25. The method of claim 24, wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 with both type 1 and type 2 IL-4 receptors. 26. The method of claim 1, 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. 27. The method of claim 26, 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. 28. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10. 29. The method of claim 1, wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof. 30. A method for treating moderate-to-severe or severe atopic dermatitis (AD) or improving an AD-associated parameter, the method comprising: (a) selecting a patient with moderate-to-severe or severe AD, wherein the patient has an attribute selected from the group consisting of: (i) the patient has a baseline IGA score=4; (ii) the patient has a baseline IGA score .gtoreq.3; (iii) the patient is between 6 and 18 years of age; (iv) the patient has disease that is uncontrolled by topical AD therapy; (v) the patient has a documented history of inadequate response to topical AD therapy or for whom topical therapy is inadvisable due to adverse side effects or safety risks; (vi) the patient has been previously treated with a medication or procedure selected from the group consisting of a topical corticosteroid, a topical calcineurin inhibitor, an anti-histamine, an emollient, a dermatological therapeutic, a systemic glucocorticoid, a non-steroidal systemic immunosuppressant, cyclosporine A, azathioprine, ultraviolet (UV) light therapy, and phototherapy; and (vii) the patient has a concomitant disease or disorder selected from the group consisting of food allergy, asthma, seasonal allergy, allergic rhinitis, house dust allergy, and allergic conjunctivitis; and (b) administering one or more doses of a therapeutically effective amount of an IL-4R inhibitor to the patient in need thereof, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that specifically binds IL-4R, 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. 31. The method of claim 30, wherein the patient has severe AD, is between 6 and 11 years of age, has a baseline IGA score=4, and has disease that is uncontrolled by topical AD therapy. 32. The method of claim 30, wherein each dose of the IL-4R inhibitor comprises 1, 2, 3, 4, or 5 mg/kg of the patient's body weight, and wherein each dose is administered 1-4 weeks after the immediately preceding dose. 33. The method of claim 30, wherein each dose comprises about 20-about 600 mg of the IL-4R inhibitor, and wherein each dose is administered 1-4 weeks after the immediately preceding dose. 34. The method of claim 30, wherein the administration of the IL-4R inhibitor leads to an effect selected from the group consisting of: (i) more than 30% reduction from baseline in EASI score by week 2 after administration of the first dose of the IL-4R inhibitor; (ii) more than 50% reduction from baseline in pruritus NRS; and (iii) a reduction from baseline in IGA score to achieve an IGA score of 0 or 1 by week 12 after administration of the first dose of the IL-4R inhibitor. 35. The method of claim 30, wherein the IL-4R inhibitor is administered in combination with a second therapeutic agent selected from the group consisting of a topical corticosteroid, a topical calcineurin inhibitor, an anti-histamine, an emollient, an anti-bacterial therapeutic, and a therapeutic agent for obstructive airway disease. 36. The method of claim 30, wherein the antibody or antigen-binding fragment prevents the interaction of IL-4 and/or IL-13 with a type 1 or type 2 IL-4 receptor. 37. The method of claim 36, wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 with both type 1 and type 2 IL-4 receptors. 38. The method of claim 30, 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. 39. The method of claim 38, 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. 40. The method of claim 30, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10. 41. The method of claim 30, wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof. 42. The method of claim 7, wherein the IL-4R inhibitor is administered at a dose of about 100 mg. 43. The method of claim 18, wherein the IL-4R inhibitor is contained in a container selected from the group consisting of a syringe, a pen delivery device, a vial, and an autoinjector. 44. The method of claim 43, wherein the IL-4R inhibitor is contained in a syringe. 45. The method of claim 43, wherein the IL-4R inhibitor is contained in a pen delivery device. 46. The method of claim 45, wherein the pen delivery device is prefilled. 47. The method of claim 43, wherein the IL-4R inhibitor is contained in a vial. 48. The method of claim 43, wherein the IL-4R inhibitor is contained in an autoinjector. 49. The method of claim 30, wherein the IL-4R inhibitor is administered subcutaneously. 50. The method of claim 49, wherein the IL-4R inhibitor is contained in a container selected from the group consisting of a syringe, a pen delivery device, a vial, and an autoinjector. 51. The method of claim 50, wherein the IL-4R inhibitor is contained in a syringe. 52. The method of claim 50, wherein the IL-4R inhibitor is contained in a pen delivery device. 53. The method of claim 52, wherein the pen delivery device is prefilled. 54. The method of claim 50, wherein the IL-4R inhibitor is contained in a vial. 55. The method of claim 50, wherein the IL-4R inhibitor is contained in an autoinjector. 56. The method of claim 33, wherein each dose comprises about 100 mg of the IL-4R inhibitor. 57. The method of claim 33, wherein each dose comprises about 200 mg of the IL-4R inhibitor.

Details for Patent 10,485,844

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	03/13/1924		2037-08-18
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	03/28/2017		2037-08-18
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	10/19/2018		2037-08-18
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	06/18/2020		2037-08-18
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	06/14/2021		2037-08-18
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	10/20/2021		2037-08-18