IP Library › Granted Patent US 12,636,280
Granted Patent B2
US 12,636,280 · App. 18/613,641 · Granted May 26, 2026

Therapeutic tyrosine kinase inhibitors for relapsing multiple sclerosis (RMS)

Inventors: Meehyung Cho (Mountainside, NJ); Timothy J. Turner (Belmont, MA); Erik Wallstroem (Cambridge, MA)
Assignee: Principia Biopharma Inc.
A61K31/4545A61P25/28
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Quick Facts
Patent No.
US 12,636,280
App. No.
18/613,641
Granted
May 26, 2026
Kind
B2
Abstract

This disclosure relates to the field of therapeutic tyrosine kinase inhibitors, in particular Bruton tyrosine kinase (“BTK”) inhibitors for treatment of subjects with relapsing multiple sclerosis.

Claims (32)

1 . A method of reducing the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions, comprising administering to a human subject in need thereof that has relapsing multiple sclerosis (RMS) an effective amount of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to placebo.

2 . The method of claim 1 , wherein the dose is 60 mg.

3 . The method of claim 2 , wherein the dose is administered once daily.

4 . The method of claim 3 , wherein the dose is administered once daily with food.

5 . The method of claim 2 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as measured by MRI, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to placebo.

6 . The method of claim 5 , wherein the number of new Gd-enhancing T1 hyperintense lesions is equal to or less than 1 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

7 . The method of claim 5 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new or enlarging T2 lesions as measured by MRI, wherein the reduction in the number of new or enlarging T2 lesions is compared to placebo.

8 . The method of claim 7 , wherein the number of new or enlarging T2 lesions is equal to or less than 2 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

9 . The method of claim 2 , wherein the dose is administered once daily, wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as measured by MRI, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to placebo.

10 . The method of claim 9 , wherein the number of new Gd-enhancing T1 hyperintense lesions is equal to or less than 1 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

11 . The method of claim 9 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new or enlarging T2 lesions as measured by MRI, wherein the reduction in the number of new or enlarging T2 lesions is compared to placebo.

12 . The method of claim 11 , wherein the number of new or enlarging T2 lesions is equal to or less than 2 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

13 . The method of claim 2 , wherein the dose is administered once daily with food, wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as measured by MRI, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to placebo.

14 . The method of claim 13 , wherein the number of new Gd-enhancing T1 hyperintense lesions is equal to or less than 1 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

15 . The method of claim 13 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new or enlarging T2 lesions as measured by MRI, wherein the reduction in the number of new or enlarging T2 lesions is compared to placebo.

16 . The method of claim 15 , wherein the number of new or enlarging T2 lesions is equal to or less than 2 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

17 . A method of reducing the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions, comprising administering to a human subject in need thereof that has relapsing multiple sclerosis (RMS) an effective amount of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to no treatment.

18 . The method of claim 17 , wherein the dose is 60 mg.

19 . The method of claim 18 , wherein the dose is administered once daily.

20 . The method of claim 19 , wherein the dose is administered once daily with food.

21 . The method of claim 18 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as measured by MRI, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to no treatment.

22 . The method of claim 21 , wherein the number of new Gd-enhancing T1 hyperintense lesions is equal to or less than 1 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

23 . The method of claim 21 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new or enlarging T2 lesions as measured by MRI, wherein the reduction in the number of new or enlarging T2 lesions is compared to no treatment.

24 . The method of claim 23 , wherein the number of new or enlarging T2 lesions is equal to or less than 2 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

25 . The method of claim 18 , wherein the dose is administered once daily, wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as measured by MRI, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to no treatment.

26 . The method of claim 25 , wherein the number of new Gd-enhancing T1 hyperintense lesions is equal to or less than 1 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

27 . The method of claim 25 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new or enlarging T2 lesions as measured by MRI, wherein the reduction in the number of new or enlarging T2 lesions is compared to no treatment.

28 . The method of claim 27 , wherein the number of new or enlarging T2 lesions is equal to or less than 2 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

29 . The method of claim 18 , wherein the dose is administered once daily with food, wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as measured by MRI, wherein the reduction in the number of new gadolinium (Gd)-enhancing T1 hyperintense lesions is compared to no treatment.

30 . The method of claim 29 , wherein the number of new Gd-enhancing T1 hyperintense lesions is equal to or less than 1 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

31 . The method of claim 29 , wherein administration of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one reduces the number of new or enlarging T2 lesions as measured by MRI, wherein the reduction in the number of new or enlarging T2 lesions is compared to no treatment.

32 . The method of claim 31 , wherein the number of new or enlarging T2 lesions is equal to or less than 2 after 12 weeks of (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one treatment.

Assignments (3)
ASSIGNEE CHANGE OF ADDRESS Recorded Sep 16, 2025
From: PRINCIPIA BIOPHARMA INC.
To: PRINCIPIA BIOPHARMA INC.
Reel/Frame 072881/0270 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 11, 2024
From: CHO, MEEHYUNG; TURNER, TIMOTHY J.; WALLSTROEM, ERIK
To: GENZYME CORPORATION
Reel/Frame 067694/0473 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 11, 2024
From: GENZYME CORPORATION
To: PRINCIPIA BIOPHARMA INC.
Reel/Frame 067694/0242 →
Continuity (5)
Continuation 17151954 · Jan 19, 2021
Provisional Application 63013895 · Apr 22, 2020
Provisional Application 62970502 · Feb 5, 2020
Provisional Application 62963238 · Jan 20, 2020
Related Publication 20240366585A1 · Nov 7, 2024
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ClinicalTrials.gov, “Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168)(HERCULES) (HERCULES)”, NCT04411641, Record History Tab, Vers… [cited by applicant]
ClinicalTrials.gov, “Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168)(HERCULES) (HERCULES)”, NCT04411641, Record History Tab, Vers… [cited by applicant]
ClinicalTrials.gov, “Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168)(HERCULES)(HERCULES)”, NCT04411641, Record History Tab, Versi… [cited by applicant]
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ClinicalTrials.gov, “Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS) (PERSEUS)”, NCT04458051, Record History Tab, Version 25, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS) (PERSEUS)”, NCT04458051, Record History Tab, Version 1, Last Update… [cited by applicant]
ClinicalTrials.gov, “Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS) (PERSEUS)”, NCT04458051, Record History Tab, Version 43, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS) (PERSEUS)”, NCT04458051, Record History Tab, Version 42, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS) (PERSEUS)”, NCT04458051, Record History Tab, Version 11, Last Updat… [cited by applicant]
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ClinicalTrials.gov, “Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)(GEMINI 1)”, NCT04410978, Records History Tab, Version 1, Last Update… [cited by applicant]
ClinicalTrials.gov, “Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)(GEMINI 1)”, NCT04410978, Records History Tab, Version 17, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)(GEMINI 1)”, NCT04410978, Records History Tab, Version 26, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 2) (GEMINI 2)”, NCT04410991, Record History Tab, Version 26, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 2) (GEMINI 2)”, NCT04410991, Record History Tab, Version 18, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)(GEMINI 1)”, NCT04410978, Records History Tab, Version 44, Last Updat… [cited by applicant]
ClinicalTrials.gov, “Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 2) (GEMINI 2)”, NCT04410991, Record History Tab, Version 1, Last Update… [cited by applicant]
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