Granted Patent B2

US 12,502,429 · App. 17/951,987 · Granted Dec 23, 2025

Inventors: Marius Ardeleanu (White Plains, NY); Neil Graham (Croton-on-Hudson, NY); Jennifer Davidson Hamilton (Ridgefield, CT); Stephane C. Kirkesseli (Paris, FR); Sudeep Kundu (New York, NY); Jeffrey Ming (Bridgewater, NJ); Allen Radin (New York, NY); Ross E. Rocklin (Basking Ridge, NJ); Steven Paul Weinstein (Hartsdale, NY)

Assignees: Regeneron Pharmaceuticals, Inc.; Sanofi Biotechnology

A61K39/3955A61K31/573A61K31/58A61K45/06C07K16/2866G01N33/53A61K2039/54C07K2317/21G01N2800/202

Abstract

Claims (56)

1 . A method of treating moderate-to-severe atopic dermatitis (AD) in a subject in need thereof, the method comprising:

administering an anti-interleukin-4-receptor (IL-4R) antibody or an antigen-binding fragment thereof to a subject having moderate-to-severe AD, wherein the subject is resistant, non-responsive, or inadequately responsive to treatment with a topical corticosteroid or a topical calcineurin inhibitor, or is a subject for whom topical treatments are inadvisable;

wherein the anti-IL-4R antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 comprising the amino acid sequence of SEQ ID NO:148, an HCDR2 comprising the amino acid sequence of SEQ ID NO:150, an HCDR3 comprising the amino acid sequence of SEQ ID NO:152, a light chain complementarity determining region (LCDR)1 comprising the amino acid sequence of SEQ ID NO:156, an LCDR2 comprising the amino acid sequence of LGS, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:160; and

wherein the anti-IL-4R antibody or antigen-binding fragment thereof is administered to the subject in a dosing regimen comprising an initial dose followed by one or more secondary doses, wherein the initial dose is 600 mg of the anti-IL-4R antibody or antigen-binding fragment thereof, the secondary dose is 300 mg of the anti-IL-4R antibody or antigen-binding fragment thereof, and each secondary dose is administered 1 to 2 weeks after the immediately preceding dose;

wherein treatment results in an improvement in an AD-associated parameter from baseline to Week 16, wherein the improvement in the AD-associated parameter is:

(i) a decrease from baseline in Eczema Area and Severity Index (EASI) score of at least 50%;

(ii) a decrease from baseline in Investigator's Global Assessment (IGA) score of ≥2; and/or

(iii) an improvement in IGA score to an IGA score of 0 or 1.

2 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is administered subcutaneously.

3 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:162 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:164.

4 . The method of claim 3 , wherein each secondary dose is administered one week after the immediately preceding dose.

5 . The method of claim 3 , wherein each secondary dose is administered two weeks after the immediately preceding dose.

6 . The method of claim 3 , wherein treatment results in a decrease from baseline to Week 16 in EASI score of at least 50%.

7 . The method of claim 3 , wherein treatment results in a decrease from baseline to Week 16 in EASI score of at least 75%.

8 . The method of claim 3 , wherein treatment results in a decrease from baseline to Week 16 in EASI score of at least 90%.

9 . The method of claim 3 , wherein treatment results in a decrease from baseline to Week 16 in IGA score of ≥2.

10 . The method of claim 3 , wherein treatment results in an improvement from baseline to Week 16 in IGA score to an IGA score of 1.

11 . The method of claim 3 , wherein treatment results in an improvement from baseline to Week 16 in IGA score to an IGA score of 0.

12 . The method of claim 3 , wherein the anti-IL-4R antibody is a full antibody.

13 . The method of claim 12 , wherein the full antibody is an IgG antibody.

14 . The method of claim 12 , wherein the full antibody is an IgG4 antibody.

15 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is administered concomitantly with a topical corticosteroid.

16 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is contained in a syringe.

17 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is contained in a glass vial.

18 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is contained in a microinfuser.

19 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is contained in a pen delivery device.

20 . The method of claim 19 , wherein the pen delivery device is pre-filled.

21 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is contained in an autoinjector.

22 . The method of claim 1 , wherein the anti-IL-4R antibody or antigen-binding fragment thereof is human.

23 . A method of treating moderate-to-severe atopic dermatitis (AD) in a subject in need thereof, the method comprising:

administering an anti-interleukin-4-receptor (IL-4R) human antibody to a subject having moderate-to-severe AD, wherein the subject is resistant, non-responsive, or inadequately responsive to treatment with a topical corticosteroid or a topical calcineurin inhibitor, or is a subject for whom topical treatments are inadvisable;

wherein the anti-IL-4R human antibody is a full antibody and comprises a heavy chain complementarity determining region (HCDR)1 comprising the amino acid sequence SEQ ID NO:148, an HCDR2 comprising the amino acid sequence SEQ ID NO:150, an HCDR3 comprising the amino acid sequence SEQ ID NO:152, a light chain complementarity determining region (LCDR)1 comprising the amino acid sequence SEQ ID NO:156, an LCDR2 comprising the amino acid sequence LGS, and an LCDR3 comprising the amino acid sequence SEQ ID NO:160; and

wherein the anti-IL-4R human antibody is administered to the subject in a dosing regimen comprising an initial dose followed by one or more secondary doses, wherein the initial dose is 600 mg of the anti-IL-4R human antibody, the secondary dose is 300 mg of the anti-IL-4R human antibody, and each secondary dose is administered 1 to 2 weeks after the immediately preceding dose;

wherein treatment results in an improvement in an AD-associated parameter from baseline to Week 16, wherein the improvement in the AD-associated parameter is:

(i) a decrease from baseline in Eczema Area and Severity Index (EASI) score of at least 50%;

(ii) a decrease from baseline in Investigator's Global Assessment (IGA) score of ≥2; and/or

(iii) an improvement in IGA score to an IGA score of 0 or 1.

24 . The method of claim 23 , wherein the anti-IL-4R human antibody comprises a heavy chain variable region (HCVR) comprising the amino acid sequence SEQ ID NO:162 and a light chain variable region (LCVR) comprising the amino acid sequence SEQ ID NO:164.

25 . The method of claim 24 , wherein the anti-IL-4R human antibody is an IgG antibody.

26 . The method of claim 24 , wherein the anti-IL-4R human antibody is an IgG4 antibody.

27 . The method of claim 26 , wherein each secondary dose is administered one week after the immediately preceding dose.

28 . The method of claim 26 , wherein each secondary dose is administered two weeks after the immediately preceding dose.

29 . The method of claim 26 , wherein the anti-IL-4R human antibody is administered subcutaneously.

30 . The method of claim 26 , wherein the anti-IL-4R human antibody is administered concomitantly with a topical corticosteroid.

31 . The method of claim 26 , wherein the anti-IL-4R human antibody is contained in a syringe.

32 . The method of claim 26 , wherein the anti-IL-4R human antibody is contained in a glass vial.

33 . The method of claim 26 , wherein the anti-IL-4R human antibody is contained in a microinfuser.

34 . The method of claim 26 , wherein the anti-IL-4R human antibody is contained in a pen delivery device.

35 . The method of claim 34 , wherein the pen delivery device is pre-filled.

36 . The method of claim 26 , wherein the anti-IL-4R human antibody is contained in an autoinjector.

37 . The method of claim 26 , wherein treatment results in a decrease from baseline to Week 16 in EASI score of at least 50%.

38 . The method of claim 26 , wherein treatment results in a decrease from baseline to Week 16 in EASI score of at least 75%.

39 . The method of claim 26 , wherein treatment results in a decrease from baseline to Week 16 in EASI score of at least 90%.

40 . The method of claim 26 , wherein treatment results in a decrease from baseline to Week 16 in IGA score of ≥2.

41 . The method of claim 26 , wherein treatment results in an improvement from baseline to Week 16 in IGA score to an IGA score of 1.

42 . The method of claim 26 , wherein treatment results in an improvement from baseline to Week 16 in IGA score to an IGA score of 0.

Assignments (3)

Priority Claims (1)

Continuity (11)

References Cited (400)