Methods of treatment of pediatric patients with upadacitinibe

Description

1 / 143 Treatment methods for pediatric patients with upadacitinib. CROSS-REFERENCE TO RELATED DEPOSIT REQUESTS

[001] This application claims the benefit of U.S. Provisional Application No. 63 / 491,665, filed March 22, 2023, and claims the benefit of U.S. Provisional Application No. 63 / 623,994, filed January 23, 2024, each of which is incorporated herein by reference in its entirety. FIELD OF REVELATION

[002] This disclosure is directed to methods for treating diseases in pediatric patients with the selective JAK1 inhibitor, upadacitinib. BACKGROUND TO THE REVELATION

[003] Upadacitinib is a selective JAK1 inhibitor approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic spondyloarthritis, and ulcerative colitis in adults, and for the treatment of atopic dermatitis in adults and adolescents 12 years of age and older weighing 40 kg or more. Upadacitinib is also under investigation for use in the treatment of adults with Crohn's disease, hidradenitis suppurativa, and systemic lupus erythematosus. Upadacitinib has not been evaluated for the treatment of pediatric patients under 12 years of age or under 18 years of age and weighing less than 40 kg.

[004] Although the pharmacokinetics, safety, and tolerability of upadacitinib in adults are known, the pharmacokinetics, safety, and tolerability of upadacitinib in pediatric patients under 12 years of age or under 18 years of age and weighing less than 40 kg have not been studied. Since the diseases identified above also occur in pediatric patients, it is desirable in the art to provide safe and effective doses of upadacitinib in pediatric patients. In particular, it is desirable to establish dosing regimens with Petition 870250084429, dated 09 / 19 / 2025, page 11 / 189 2 / 143 based on weight that provide comparable plasma exposure in pediatric patients to doses determined to be effective in adults (i.e., 15 mg and 30 mg once daily). Furthermore, tablet formulations may be difficult to swallow for younger pediatric patients, which may result in poor patient adherence and reduced therapeutic efficacy. SUMMARY OF REVELATION

[005] The present disclosure provides methods for treating a disease or disorder in a pediatric patient who requires it with upadacitinib. The diseases and disorders include idiopathic arthritis (pcJIA), systemic juvenile idiopathic arthritis (SJIA), juvenile psoriatic arthritis (JPsA), atopic dermatitis (AD), juvenile ankylosing spondylitis (JAS), juvenile non-radiographic spondyloarthritis (nraxSpA), hidradenitis suppurativa (HS), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn's disease (CD).Treatment methods generally involve administering a therapeutically effective amount of upadacitinib to a pediatric patient as a stable liquid pharmaceutical composition or a solid dosage form, at a dose based on the patient's body weight. Specifically, treatment methods for pediatric patients in need of such a therapeutically effective amount of upadacitinib, in an amount based on body weight category, as a stable liquid pharmaceutical composition twice daily or as a once-daily extended-release tablet, are provided here.

[006] In one aspect, a method is provided for the treatment of polyarticular juvenile idiopathic arthritis (pcJIA) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadaciti Petition 870250084429, dated 09 / 19 / 2025, page 12 / 189 3 / 143 nibe to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[007] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily).

[008] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[009] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily). Petition 870250084429, dated 09 / 19 / 2025, page 13 / 189 4 / 143

[010] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[011] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day).

[012] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[013] In some modalities, if the pediatric patient has color weight Petition 870250084429, dated 09 / 19 / 2025, p. 14 / 189 5 / 143 For pediatric patients weighing approximately 10 kg to less than approximately 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient weighs approximately 20 kg to less than approximately 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient weighs approximately 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily) or once daily at a dose of 30 mg (30 mg once daily).

[014] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[015] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[016] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[017] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[018] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[019] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or Petition 870250084429, dated 09 / 19 / 2025, page 15 / 189 6 / 143 (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[020] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[021] In some modalities, pcJIA is polyarticular JIA positive for rheumatoid factor or negative for rheumatoid factor.

[022] In some modalities, the pediatric patient has a history of arthritis affecting at least 5 joints in the first 6 months of the disease.

[023] In some modalities, the pediatric patient does not have a diagnosis of enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (JPSA).

[024] In some modalities, the pediatric patient has: a) 5 or more active joints, as defined by the presence of swollen joints not due to deformity; or b) In the absence of swelling, joints with limitation of movement (LOM) plus pain on movement and / or tenderness on palpation, with LOM present in at least three of the active joints.

[025] In some modalities, the pediatric patient is receiving a stable dose of < 20 mg / m2 of methotrexate for at least 8 weeks before the start of administration.

[026] In some modalities, the pediatric patient is receiving a stable dose of oral glucocorticoids not exceeding 10 mg / day or 0.2 mg / kg / day, whichever is lower, for at least 1 week prior to the start of administration.

[027] In some modalities, the pediatric patient achieves one or more of the following: a pediatric JIA ACR response of 30 / 50 / 70 / 90 / 100, a change from baseline in JADAS responses10 / 27 / 71, low disease activity according to criteria Petition 870250084429, dated 09 / 19 / 2025, p. 16 / 189 7 / 143 based on JADAS or remission according to JADAS-based criteria. In some modalities, the pediatric patient achieves one or more of the following: a pediatric JIA ACR response of 30 / 50 / 70 / 90 / 100, a change from baseline in JADAS responses10 / 27 / 71, low disease activity according to JADAS-based criteria, or remission according to JADAS-based criteria, achieved at 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, 48 ​​weeks, or 52 weeks after the first daily administration. In some modalities, the pediatric patient achieves a pediatric JIA ACR response of 30 at 12 weeks after the first daily administration. In some modalities, the pediatric patient achieves a pediatric JIA ACR response of 50 at 12 weeks after the first daily administration. In some modalities, the pediatric patient achieves a JIA ACR pediatric response of 70 within 12 weeks after the first daily administration.In some modalities, the pediatric patient achieves a JIA ACR pediatric response of 90 within 12 weeks after the first daily administration. In some modalities, the pediatric patient achieves a JIA ACR pediatric response of 100 within 12 weeks after the first daily administration.

[028] In some embodiments, the pediatric patient achieves a pediatric JIA ACR response of 30 within 24 weeks after the first daily administration. In some embodiments, the pediatric patient achieves a pediatric JIA ACR response of 50 within 24 weeks after the first daily administration. In some embodiments, the pediatric patient achieves a pediatric JIA ACR response of 70 within 24 weeks after the first daily administration. In some embodiments, the pediatric patient achieves a pediatric JIA ACR response of 90 within 24 weeks after the first daily administration. In some embodiments, the pediatric patient achieves a pediatric JIA ACR response of 100 within 24 weeks after the first daily administration.

[029] In some modalities, the pediatric patient achieves a pediatric JIA ACR response 30 in 48 weeks after the first daily administration. In some Petition 870250084429, dated 09 / 19 / 2025, page 17 / 189 In 8 / 143 modalities, the pediatric patient achieves a JIA ACR pediatric response of 50 within 48 weeks after the first daily administration. In some modalities, the pediatric patient achieves a JIA ACR pediatric response of 70 within 48 weeks after the first daily administration. In some modalities, the pediatric patient achieves a JIA ACR pediatric response of 90 within 48 weeks after the first daily administration. In some modalities, the pediatric patient achieves a JIA ACR pediatric response of 100 within 48 weeks after the first daily administration.

[030] In another aspect, a method is provided for treating systemic juvenile idiopathic arthritis (SJIA) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[031] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily).

[032] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg. Petition 870250084429, dated 09 / 19 / 2025, page 18 / 189 9 / 143 each (4 mg twice daily); or (ii) upadacitinib is administered twice daily at a dose of 8 mg each (8 mg twice daily).

[033] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[034] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[035] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day). Petition 870250084429, dated 09 / 19 / 2025, p. 19 / 189 10 / 143

[036] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[037] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[038] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[039] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[040] In some modalities, the oral solution comprises upadacitinib, Petition 870250084429, dated 09 / 19 / 2025, page 20 / 189 11 / 143 a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[041] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[042] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[043] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[044] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[045] In another aspect, a method is provided for treating atopic dermatitis (AD) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[046] In some modalities, the pediatric patient is less than twelve years of age and has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg. Petition 870250084429, dated 09 / 19 / 2025, page 21 / 189 12 / 143 each (3 mg twice daily); or (ii) upadacitinib is administered twice daily at a dose of 6 mg each (6 mg twice daily).

[047] In some modalities, the pediatric patient is less than twelve years of age and has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[048] In some modalities, the pediatric patient is under twelve years of age and has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[049] In some modalities, the pediatric patient is under twelve years of age and has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily). Petition 870250084429, dated 09 / 19 / 2025, page 22 / 189 13 / 143

[050] In some embodiments, if the pediatric patient is under twelve years of age and has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily); if the pediatric patient is under twelve years of age and has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily); and if the pediatric patient is under twelve years of age and has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily) or once daily at a dose of 15 mg (15 mg once daily).

[051] In some embodiments, if the pediatric patient is under twelve years of age and has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); if the pediatric patient is under twelve years of age and has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient is under twelve years of age and has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily) or once daily at a dose of 30 mg (30 mg once daily).

[052] In some embodiments, if the pediatric patient is under twelve years of age and weighs between approximately 10 kg and less than approximately 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); if the pediatric patient is under twelve years of age and weighs between approximately 20 kg and less than approximately 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient is under twelve Petition 870250084429, dated 09 / 19 / 2025, p. 23 / 189 For individuals aged 14 to 143 years and weighing approximately 30 kg or more, the treatment involves administering upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily) or once daily at a dose of 30 mg (30 mg once daily).

[053] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day).

[054] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[055] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient Petition 870250084429, dated 09 / 19 / 2025, p. 24 / 189 For individuals weighing approximately 30 kg or more (15 / 143), the recommended treatment involves administering upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily) or once daily at a dose of 30 mg (30 mg once daily).

[056] In some embodiments, if the pediatric patient is twelve years of age or older and has a body weight of less than about 40 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[057] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[058] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[059] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[060] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[061] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[062] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily). Petition 870250084429, dated 09 / 19 / 2025, page 25 / 189 16 / 143 mg once a day.

[063] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[064] In some embodiments, the pediatric patient achieves an EASI response of 75 at 12 weeks after the first daily administration. In some embodiments, the pediatric patient achieves an EASI response of 90 at 12 weeks after the first daily administration. In some embodiments, the pediatric patient achieves an EASI response of 100 at 12 weeks after the first daily administration. In some embodiments, the pediatric patient achieves a score on the Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scale of 0 or 1 at 12 weeks after the first daily administration.

[065] In another aspect, a method is provided for the treatment of juvenile psoriatic arthritis (JPsA) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[066] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily). Petition 870250084429, dated 09 / 19 / 2025, page 26 / 189 17 / 143

[067] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[068] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[069] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[070] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib Petition 870250084429, dated 09 / 19 / 2025, p. 27 / 189 18 / 143 twice daily at a dose of 4 mg each time (4 mg twice daily); and if the pediatric patient has a body weight of approximately 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily) or once daily at a dose of 15 mg (15 mg once daily).

[071] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[072] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[073] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[074] In some modalities, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, two Petition 870250084429, dated 09 / 19 / 2025, page 28 / 189 19 / 143 times a day at a dose of 6 mg of upadacitinib, twice a day at a dose of 8 mg of upadacitinib, or twice a day at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[075] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[076] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[077] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[078] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[079] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[080] In another aspect, a method is provided for the treatment of juvenile ankylosing spondylitis (JAS) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form. Petition 870250084429, dated 09 / 19 / 2025, page 29 / 189 20 / 143

[081] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily).

[082] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[083] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[084] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or Petition 870250084429, dated 09 / 19 / 2025, page 30 / 189 21 / 143 (ii) upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg 2x / day).

[085] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day).

[086] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[087] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering Petition 870250084429, dated 09 / 19 / 2025, p. 31 / 189 22 / 143 upadacitinib twice daily at a dose of 12 mg each time (12 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[088] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[089] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[090] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[091] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[092] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[093] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[094] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet. Petition 870250084429, dated 09 / 19 / 2025, page 32 / 189 23 / 143

[095] In another aspect, a method is provided for the treatment of non-radiographic axial spondyloarthritis (nr-axSpA) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[096] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily).

[097] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[098] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg. Petition 870250084429, dated 09 / 19 / 2025, page 33 / 189 24 / 143 each (6 mg twice daily); or (ii) upadacitinib is administered twice daily at a dose of 8 mg each (8 mg twice daily).

[099] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[0100] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day).

[0101] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily) or once daily. Petition 870250084429, dated 09 / 19 / 2025, p. 34 / 189 25 / 143 per day at a dose of 30 mg (30 mg once a day).

[0102] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[0103] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[0104] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[0105] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener, and water.

[0106] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[0107] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[0108] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: Petition 870250084429, dated 09 / 19 / 2025, page 35 / 189 26 / 143 (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[0109] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[0110] In another aspect, a method is provided for the treatment of hidradenitis suppurativa (HS) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[0111] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily).

[0112] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg. Petition 870250084429, dated 09 / 19 / 2025, page 36 / 189 27 / 143 each (4 mg twice daily); or (ii) upadacitinib is administered twice daily at a dose of 8 mg each (8 mg twice daily).

[0113] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[0114] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[0115] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day). Petition 870250084429, dated 09 / 19 / 2025, p. 37 / 189 28 / 143

[0116] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[0117] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[0118] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[0119] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[0120] In some embodiments, the oral solution comprises upadacitinib, Petition 870250084429, dated 09 / 19 / 2025, page 38 / 189 29 / 143 a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[0121] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[0122] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[0123] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[0124] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[0125] In another aspect, a method is provided for the treatment of systemic lupus erythematosus (SLE) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[0126] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg. Petition 870250084429, dated 09 / 19 / 2025, page 39 / 189 30 / 143 each (3 mg twice daily); or (ii) upadacitinib is administered twice daily at a dose of 6 mg each (6 mg twice daily).

[0127] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[0128] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[0129] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[0130] In some modalities, if the pediatric patient has a color weight Petition 870250084429, dated 09 / 19 / 2025, page 40 / 189 31 / 143 For pediatric patients weighing approximately 10 kg to less than approximately 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient weighs approximately 20 kg to less than approximately 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily); and if the pediatric patient weighs approximately 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily) or once daily at a dose of 15 mg (15 mg once daily).

[0131] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[0132] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[0133] In some modalities, the therapeutically effective amount of Petition 870250084429, dated 09 / 19 / 2025, p. 41 / 189 32 / 143 upadacitinib is administered to pediatric patients as a stable oral pharmaceutical solution.

[0134] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[0135] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[0136] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[0137] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[0138] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[0139] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[0140] In yet another aspect, a method is provided for the treatment of ulcerative colitis (UC) in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount Petition 870250084429, dated 09 / 19 / 2025, page 42 / 189 33 / 143 of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[0141] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily).

[0142] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[0143] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[0144] In some modalities, the pediatric patient has a body weight of Petition 870250084429, dated 09 / 19 / 2025, page 43 / 189 34 / 143 approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[0145] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day).

[0146] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[0147] In some modalities, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 Petition 870250084429, dated 09 / 19 / 2025, p. 44 / 189 35 / 143 mg BID); if the pediatric patient weighs between approximately 20 kg and less than approximately 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient weighs approximately 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily) or once daily at a dose of 30 mg (30 mg once daily).

[0148] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[0149] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[0150] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener, and water.

[0151] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[0152] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL.

[0153] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily). Petition 870250084429, dated 09 / 19 / 2025, page 45 / 189 36 / 143

[0154] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[0155] In yet another aspect, a method is provided for the treatment of Crohn's disease in a pediatric patient, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable liquid pharmaceutical composition. In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a solid dosage form.

[0156] In some modalities, the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprising administering a therapeutically effective amount of upadacitinib, wherein: (i) Upadacitinib is administered twice daily at a dose of 3 mg each time (3 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily).

[0157] In some modalities, the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 4 mg each time (4 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[0158] In some modalities, the pediatric patient has a body weight of Petition 870250084429, dated 09 / 19 / 2025, page 46 / 189 37 / 143 approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 8 mg each time (8 mg twice daily).

[0159] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) Upadacitinib is administered twice daily at a dose of 6 mg each time (6 mg twice daily); or (ii) Upadacitinib is administered twice daily at a dose of 12 mg each time (12 mg twice daily).

[0160] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 3 mg each time (3 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 4 mg each time (4 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg 2x / day) or once daily at a dose of 15 mg (15 mg 1x / day).

[0161] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib Petition 870250084429, dated 09 / 19 / 2025, p. 47 / 189 38 / 143 twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient has a body weight of approximately 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily) or once daily at a dose of 30 mg (30 mg once daily).

[0162] In some embodiments, if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg, the method comprises administering upadacitinib twice daily at a dose of 6 mg each time (6 mg BID); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg, the method comprises administering upadacitinib twice daily at a dose of 8 mg each time (8 mg 2x / day); and if the pediatric patient has a body weight of about 30 kg or more, the method comprises administering upadacitinib twice daily at a dose of 12 mg each time (12 mg 2x / day) or once daily at a dose of 30 mg (30 mg 1x / day).

[0163] In some embodiments, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a stable oral pharmaceutical solution.

[0164] In some embodiments, twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib is given to the pediatric patient as a stable oral pharmaceutical solution.

[0165] In some embodiments, the oral solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener, and water.

[0166] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL.

[0167] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL. Petition 870250084429, dated 09 / 19 / 2025, page 48 / 189 39 / 143

[0168] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein: (i) upadacitinib is administered once daily at a dose of 15 mg (15 mg once daily); or (ii) upadacitinib is administered once daily at a dose of 30 mg (30 mg once daily).

[0169] In some modalities, the therapeutically effective amount of upadacitinib is administered to the pediatric patient as a prolonged-release tablet.

[0170] In yet another aspect, a stable oral pharmaceutical formulation is provided comprising upadacitinib or a pharmaceutically acceptable salt or solid form thereof, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

[0171] In some embodiments, the stable oral pharmaceutical formulation comprises the anhydrous free base of upadacitinib at a concentration of approximately 0.5 mg / mL.

[0172] In some embodiments, the stable oral pharmaceutical formulation comprises the anhydrous free base of upadacitinib at a concentration of approximately 1 mg / mL.

[0173] In some embodiments, the buffer is selected from the group consisting of citrate, phosphate, tartrate, succinate, formate, acetate and combinations thereof.

[0174] In some embodiments, the pH adjusting agent is selected from the group consisting of citric acid, phosphoric acid, tartaric acid, succinic acid, formic acid, acetic acid and combinations thereof.

[0175] In some embodiments, the preservative is selected from the group consisting of sodium benzoate, benzoic acid, propyl paraben, sodium metabisulfite, Petition 870250084429, dated 09 / 19 / 2025, page 49 / 189 40 / 143 potassium sorbate, para-hydroxybenzoic acid, para-hydroxybenzoate and combinations thereof.

[0176] In some embodiments, the sweetener is selected from the group consisting of sucralose, acesulfame potassium, sodium saccharin, neotame, sucrose, maltitol, xylitol and combinations thereof.

[0177] In some embodiments, the stable oral pharmaceutical formulation comprises anhydrous freebase upadacitinib, citric acid, sodium citrate, sodium benzoate, sucralose, and water.

[0178] In some embodiments, the stable oral pharmaceutical solution has a pH in a range of about 2 to about 5. In some embodiments, the stable oral pharmaceutical solution has a pH in a range of about 3 to about 4. In some embodiments, the stable oral pharmaceutical solution has a pH in a range of about 2.5 to about 3.5. BRIEF DESCRIPTION OF THE DRAWINGS

[0179] Figure 1 is a schematic illustration of a clinical study in pediatric patients with polyarticular juvenile idiopathic arthritis according to a non-limiting development modality.

[0180] Figure 2 is a graphical representation of the mean plasma concentration profiles of upadacitinib as a function of time in pediatric patients with polyarticular juvenile idiopathic arthritis according to non-limiting development modalities.

[0181] Figures 3A to 3E are graphical representations of upadacitinib efficacy at week 12 according to various measures and stratified by age group in pediatric patients with polyarticular juvenile idiopathic arthritis according to non-limiting development modalities.

[0182] Figure 4 is a schematic illustration of a clinical study in pediatric patients with atopic dermatitis according to a non-limiting modality. Petition 870250084429, dated 09 / 19 / 2025, page 50 / 189 41 / 143 of the revelation.

[0183] Figures 5A to 5D are graphical representations of mean plasma concentration profiles of upadacitinib as a function of time in pediatric patients with atopic dermatitis according to non-limiting disclosure modalities.

[0184] Figure 6 is a schematic illustration of a clinical study in pediatric patients with polyarticular juvenile idiopathic arthritis according to a non-limiting development modality.

[0185] Figure 7 is a schematic illustration of the patient's arrangement in the clinical study of Example 1.

[0186] Figures 8A to 8C are graphical representations of mean plasma concentration profiles of upadacitinib as a function of time in pediatric patients with polyarticular juvenile idiopathic arthritis for various formulations according to non-limiting development modalities.

[0187] Figures 9A to 9E are a series of graphical representations of upadacitinib efficacy at week 12 according to various measures and stratified by age group in pediatric patients with polyarticular juvenile idiopathic arthritis according to non-limiting development modalities.

[0188] Figure 10A is a graphical representation of the efficacy of upadacitinib over time up to week 48 according to the JIA ACR response rate in pediatric patients with polyarticular juvenile idiopathic arthritis according to non-limiting development modalities.

[0189] Figure 10B is a graphical representation of the efficacy of upadacitinib over time up to week 48 according to the JADAS27 [CRP] response rate in pediatric patients with polyarticular juvenile idiopathic arthritis according to non-limiting development modalities.

[0190] Figure 10C is a graphical representation of the efficacy of upadacitinib over time up to week 48 according to the mean change in C-CHAQ a Petition 870250084429, dated 09 / 19 / 2025, page 51 / 189 42 / 143 from baseline in pediatric patients with polyarticular juvenile idiopathic arthritis according to non-limiting developmental modalities.

[0191] Figure 10D is a graphical representation of the efficacy of upadacitinib over time up to week 48 according to the mean change in the total number of active joints from baseline in pediatric patients with polyarticular juvenile idiopathic arthritis according to non-limiting development modalities. DETAILED DESCRIPTION OF THE REVELATION I. Definitions

[0192] The section headings used in this section and the entire disclosure are not intended to be limiting.

[0193] Where a numerical range is recited, each intervening number in the range is explicitly contemplated with the same degree of precision. For example, for the range 6 to 9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0 to 7.0, the numbers 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9 and 7.0 are explicitly contemplated. Similarly, all cited ratios also include all sub-ratios encompassed by the broader ratio.

[0194] The singular forms a / an and the / the include plural referents, unless the context clearly indicates otherwise.

[0195] The term about generally refers to a range of numbers that someone skilled in the art would consider equivalent to the recited value (i.e., with the same function or result). In many cases, the term about may include numbers rounded to the nearest significant digit.

[0196] Unless the context requires otherwise, the terms understand, understands and understanding are used on the basis and clear understanding that they should be interpreted inclusively, not exclusively, and that the Applicant intends that each of these words be interpreted in this way in the interpretation of this patent, including the claims below. Petition 870250084429, dated 09 / 19 / 2025, page 52 / 189 43 / 143

[0197] The term AUC refers to the area under the curve. AUC is the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time.

[0198] The term Cmax refers to the plasma concentration of the drug relative to Tmax, expressed here as ng / ml, produced by oral ingestion of a single dose, or number of doses indicated, of the dosage form or pharmaceutical composition, such as the dosage forms and compositions of this disclosure. Unless specifically indicated, Cmax refers to the maximum observed total concentration.

[0199] The terms treating, treatment and therapy and the like, as used herein, are intended to include therapeutic measures for a disease or disorder leading to any desirable or beneficial clinical effect, including but not limited to relief or decrease of one or more symptoms, regression, slowing or cessation of the progression of the disease or disorder.

[0200] As used herein, the term pediatric patient refers to a human patient under 18 years of age. The terms patient and individual are used interchangeably herein.

[0201] The term pharmaceutically acceptable salts refers to those salts that retain the biological efficacy and properties of free bases and that are obtained by reaction with inorganic acids, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid, or organic acids, such as sulfonic acid, carboxylic acid, organic phosphoric acid, methanesulfonic acid, ethanesulfonic acid, ptoluenesulfonic acid, citric acid, fumaric acid, maleic acid, succinic acid, benzoic acid, salicylic acid, lactic acid, monomalic acid, monooxalic acid, tartaric acid, such as monotartaric acid (for example, (+) or (-)-tartaric acid or mixtures thereof), amino acids (for example, (+) or (-)-amino acids or mixtures thereof) and the like. These salts can be prepared by methods known to the versa Petition 870250084429, dated 09 / 19 / 2025, page 53 / 189 44 / 143 of the techniques. Examples of pharmaceutically acceptable salts of upadacitinib can be found in WO 2017 / 066775, which is incorporated herein by reference in its entirety. II. JAK1 Inhibition

[0202] Upadacitinib (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide), or a pharmaceutically acceptable salt or solid form thereof, is an oral Janus kinase (JAK) inhibitor that exhibits exclusive selectivity for the JAK1 receptor. Upadacitinib has the structure shown below:

[0203] The upadacitinib dosage intensity cited in this application is based on the weight of anhydrous free base upadacitinib present in the active ingredient released to the patient. For example, a dose of 15 mg of upadacitinib or UPA 15 mg refers to the amount of 15 mg of neutral free base upadacitinib present in the active ingredient, not including any coformers (e.g., solvent or water molecule(s)) of a solvate or hydrate (including hemihydrate) or counter-anions of a pharmaceutically acceptable salt), which may also be present in the active ingredient. Thus, for example, administering 15 mg of upadacitinib involves administering 15.4 mg of crystalline upadacitinib freebase hemihydrate (which includes 1 / 2 of a water conformer molecule per upadacitinib freebase molecule) that delivers 15 mg of anhydrous freebase upadacitinib to a patient.In another example, a dose of 30 mg of upadacitinib, or UPA 30 mg, refers to the amount of 30 mg of the neutral free base of upadacitinib present. Petition 870250084429, dated 09 / 19 / 2025, page 54 / 189 45 / 143 in the active ingredient, not including any co-formers (e.g., solvent or water molecule(s)) of a solvate or hydrate (including hemihydrate) or counter-anions of a pharmaceutically acceptable salt), which may also be present in the active ingredient. Thus, for example, the administration of 30 mg of upadacitinib includes the administration of 30.7 mg of crystalline upadacitinib freebase hemihydrate (which includes 1 / 2 of a water conformer molecule per upadacitinib freebase molecule) that delivers 30 mg of anhydrous upadacitinib freebase to a patient. III. Pharmaceutical compositions and routes of administration

[0204] Upadacitinib may be administered to a human patient alone or in a pharmaceutical composition where biologically suitable carriers or excipient(s) are mixed in doses to treat or alleviate a disease or condition, as described herein. Mixtures of these compounds may also be administered to the patient as a simple mixture or in appropriately formulated pharmaceutical compositions.

[0205] The pharmaceutical compositions of the present disclosure can be manufactured by a method that is itself known, for example, by means of conventional processes of mixing, dissolving, granulating, producing dragees, levigating, emulsifying, encapsulating, trapping or lyophilizing.

[0206] Pharmaceutical compositions for use according to the present disclosure can thus be formulated using a conventional method with the use of one or more physiologically acceptable carriers comprising excipients and auxiliaries that facilitate the processing of the active compounds into preparations that can be used pharmaceutically. The appropriate formulation depends on the chosen route of administration.

[0207] In some embodiments, the pharmaceutical composition is a capsule dosage form. In some embodiments, the pharmaceutical composition is a Petition 870250084429, dated 09 / 19 / 2025, page 55 / 189 46 / 143 Tablet dosage form. In some embodiments, the tablet is a controlled-release formulation, such as a prolonged-release tablet dosage form (also referred to in this document as a modified-release or sustained-release formulation). Examples of solid dosage forms comprising upadacitinib can be found in WO 2017 / 066775, which is incorporated herein by reference in its entirety.

[0208] In some embodiments, the composition is a stable liquid pharmaceutical composition. In some embodiments, the stable liquid pharmaceutical composition is a stable oral solution. In some embodiments, the stable liquid pharmaceutical composition is a stable oral suspension. Suitable stable liquid pharmaceutical compositions comprise upadacitinib or a pharmaceutically acceptable salt or solid form thereof, together with excipients such as buffers, preservatives, sweeteners, flavoring agents, pH adjusters, solvents and the like. In some embodiments, the stable liquid pharmaceutical composition is a stable oral pharmaceutical solution comprising upadacitinib, a buffer and / or pH adjuster, a preservative, a sweetener and water.In some embodiments, the stable liquid pharmaceutical composition is a stable oral pharmaceutical suspension comprising upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener, and water.

[0209] The concentration of upadacitinib in the stable liquid pharmaceutical composition may vary. Due to the bitterness of upadacitinib, which is difficult to mask at higher concentrations for palatability (see, for example, Example 6), it is generally present at about 1 mg / mL or less. In some embodiments, the stable pharmaceutical composition is an oral solution comprising: upadacitinib at a concentration in a range of about 0.3 mg / mL to about 1.2 mg / mL, such as from about 0.3 to about 0.7 mg / mL, or from about 0.8 to about 1.2 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about Petition 870250084429, dated 09 / 19 / 2025, page 56 / 189 47 / 143 mg / mL, such as from about 0.8, 0.9 or about 1.0 to about 1.1, or about 1.2 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.9 mg / mL to about 1.1 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 1.0 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, such as from about 0.3, 0.4 or about 0.5 to about 0.6, or about 0.7 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.4 mg / mL to about 0.6 mg / mL. In some formulations, the oral solution comprises upadacitinib at a concentration of 0.5 mg / mL.

[0210] In some embodiments, the oral solution additionally comprises a pH adjusting agent. Suitable pH adjusting agents include acids, such as mineral or organic acids. Mineral acids include, but are not limited to, hydrochloric, sulfuric, and phosphoric acids. As used herein, the term organic acid refers to an organic (i.e., carbon-based) compound that is characterized by acidic properties. Typically, organic acids are relatively weak acids (i.e., they do not dissociate completely in the presence of water), such as carboxylic acids (-CO2H). In some embodiments, the pH adjusting agent is an organic acid.Suitable organic acids include, but are not limited to, benzoic acid, toluic acids, salicylic acid, benzenesulfonic acid, p-toluenesulfonic acid, 2-(4-isobutylphenyl)propanoic acid, 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4-aminosalicylic acid, adipic acid, ascorbic acid (L), aspartic acid (L), alpha-methylbutyric acid, camphoric acid (+), camphor-10-sulfonic acid (+), cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, fumaric acid, furoic acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, acid glutamic, glutaric acid, glycerophosphoric acid, glycolic acid, acid. Petition 870250084429, dated 09 / 19 / 2025, page 57 / 189 48 / 143 hippuric acid, isobutyric acid, isovaleric acid, lactobionic acid, lauric acid, levulinic acid, malic acid, maleic acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, oleic acid, palmitic acid, pamoic acid, phenylacetic acid, pyroglutamic acid, pyruvic acid, sebacic acid, stearic acid, tartaric acid, and undecylenic acid. In some embodiments, the pH adjusting agent is selected from the group consisting of citric acid, phosphoric acid, tartaric acid, succinic acid, formic acid, acetic acid, and combinations thereof. In some embodiments, the pH adjusting agent is citric acid.

[0211] In some embodiments, the stable liquid pharmaceutical composition comprises a buffer. Suitable buffers include, but are not limited to, citrate, phosphate, tartrate, succinate, glycinate, glycerophosphate, formate, and acetate. In some embodiments, the buffer is selected from the group consisting of citrate, phosphate, tartrate, succinate, formate, acetate, and combinations thereof. In some embodiments, the buffer is selected from the group consisting of citrate and phosphate. In some embodiments, the buffer is sodium citrate.

[0212] The amount of pH adjusting agent and / or buffer may vary. Generally, the concentration of each is adjusted to provide a desired pH range for the resulting stable liquid pharmaceutical composition. In some embodiments, the stable liquid pharmaceutical composition has a pH in the range of about 2 to about 5, or about 3 to about 4, or about 2 to about 3, or about 4 to about 5, or about 2.0 to about 2.5, or about 2.5 to about 3.0, or about 3.0 to about 3.5, or about 3.5 to about 4.0, or about 4.0 to about 4.5, or about 4.5 to about 5.0, or about 3.0 to about 3.1, or about 3.0 to about 3.2, or about 3.0 to about 3.3, or about 3.1 to about 3.2, or about 3.1 to about 3.3, or about 3.1 to about 3.4, or about 3.1 to about 3.5, or about Petition 870250084429, dated 09 / 19 / 2025, p. 58 / 189 49 / 143 3.2 to about 3.3, or about 3.2 to about 3.4, or about 3.2 to about 3.5, or about 3.3 to about 3.4, or about 3.3 to about 3.5. In some embodiments, the stable liquid pharmaceutical composition has a pH of about 3.0, or about 3.1, or about 3.2.

[0213] In some embodiments, the stable liquid pharmaceutical composition comprises a preservative. Suitable preservatives include, but are not limited to, benzoic acid, sodium benzoate, benzyl alcohol, ascorbic acid, potassium sorbate, 4-hydroxybenzoic acid, 4-hydroxybenzoate, methylparaben, propylparaben, sodium metabisulfite, and combinations thereof. In some embodiments, the preservative is selected from the group consisting of sodium benzoate, benzoic acid, propylparaben, sodium metabisulfite, potassium sorbate, para-hydroxybenzoic acid, para-hydroxybenzoate, and combinations thereof.

[0214] In some embodiments, the stable liquid pharmaceutical composition comprises a sweetener. The sweetener may be any sweetener or combination of sweeteners, in natural or artificial form, or as a combination of natural and artificial sweeteners. Examples of natural sweeteners include fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, and the like. Examples of artificial sweeteners include sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, and the like. In some embodiments, the sweetener comprises one or more sugar alcohols. Sugar alcohols are polyols derived from monosaccharides or disaccharides that have a partially or fully hydrogenated form.Sugar alcohols, for example, have from about 4 to about 20 carbon atoms, and include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof (e.g., hydrogenated starch hydrolysates). In some embodiments, the sweetener is selected from the group consisting of sucralose, acesulfame potassium, sodium saccharin, neotame, sucrose, maltitol, xylitol, and combinations thereof. Petition 870250084429, dated 09 / 19 / 2025, page 59 / 189 50 / 143

[0215] In some embodiments, the stable oral pharmaceutical solution comprises one or more flavoring agents. Any flavoring or aromatic substance capable of altering the taste, fragrance, or both of the solution may be used. Flavoring agents may be natural or synthetic. Suitable flavoring agents include, but are not limited to, flavor packets that impart flavors such as cherry, orange, lemon, lime, bubblegum, grape, strawberry, mango, and the like.

[0216] In some embodiments, the stable oral pharmaceutical solution comprises a flavor modifier. Suitable flavor modifiers include, but are not limited to, salts such as sodium chloride and monoammonium glycyrrhizinate, to enhance sweetness.

[0217] In some embodiments, the stable pharmaceutical composition is an oral solution comprising upadacitinib, citric acid, sodium citrate, sodium benzoate, sweetener and water.

[0218] In some embodiments, the stable pharmaceutical composition comprises citric acid in an amount in the range of about 0.1 to about 1 mg / mL.

[0219] In some embodiments, the stable pharmaceutical composition comprises sodium citrate in an amount in the range of about 0.01 to about 1 mg / mL.

[0220] In some embodiments, the stable pharmaceutical composition comprises sodium benzoate in an amount in the range of about 0.01 to about 0.1 mg / mL.

[0221] In some embodiments, the stable pharmaceutical composition comprises a sweetener in an amount in the range of about 1 to about 50 mg / mL.

[0222] In particular embodiments, the stable pharmaceutical composition is an oral solution with the formulation provided in Table 1. Table 1. Formulation of upadacitinib oral solution (1 mg / mL) Component mg / mL Petition 870250084429, dated 09 / 19 / 2025, page 60 / 189 51 / 143 Upadacitinib 0.3 to 1.2 ml, citric acid, anhydrous 0.15 to 0.35 ml, sodium citrate dihydrate 0.03 to 0.06 ml, sodium benzoate 0.02 to 0.06 ml, sucralose 7 to 11 ml, purified water qs to 1 mL

[0223] The pH of the stable oral solution may vary. In some embodiments, the stable oral solution has a pH in a range of about 2 to about 5. In some embodiments, the stable oral solution has a pH in a range of about 3 to about 4. In some embodiments, the stable oral solution has a pH in a range of about 2.5 to about 3.5. IV. Pediatric Dosage

[0224] In some modalities, the pediatric patient is under 18 years of age. In some modalities, the pediatric patient is under 12 years of age. In some modalities, the pediatric patient is under 6 years of age. In some modalities, the pediatric patient is in a range of about 2 to less than about 6 years, in a range of about 6 to less than about 12 years, or in a range of about 12 to less than about 18 years. In some modalities, the pediatric patient is aged between approximately 2 and approximately 18 years, such as approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, approximately 7, approximately 8, approximately 9, approximately 10, approximately 11, approximately 12, approximately 13, approximately 14, approximately 15, approximately 16, approximately 17, or approximately 18 years of age. In some modalities, the pediatric patient is two years of age or older.In some modalities, the pediatric patient is in the age range of approximately 2 to less than 12 years old.

[0225] In some modalities, the pediatric patient has a body weight of at least about 10 kg. In some modalities, the pediatric patient has a Petition 870250084429, dated 09 / 19 / 2025, p. 61 / 189 52 / 143 Body weight from about 10 kg to less than about 30 kg, such as from about 20 to less than about 20 kg, or from about 20 to less than about 30 kg. In some modalities, the pediatric patient has a body weight of 30 kg or more. In some modalities, the pediatric patient is aged between about 2 and less than 12 years and weighs less than 40 kg. In some modalities, the pediatric patient is 12 years of age or older and weighs less than 40 kg.

[0226] In some modalities, the pediatric patient has a body weight in a range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution.

[0227] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, such as about 0.8, 0.9 or about 1.0 to about 1.1, or about 1.2 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.9 mg / mL to about 1.1 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 1.0 mg / mL.

[0228] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 3 mg dose is given twice daily as approximately 3 mL of the approximately 1 mg / mL solution.

[0229] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, such as about 0.3, 0.4 or about 0.5 to about 0.6, or about 0.7 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.4 mg / mL to about 0.6 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 0.5 mg / mL.

[0230] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 3 mg dose is given twice daily as approximately 6 mL of the approximately 0.5 mg / mL solution. Petition 870250084429, dated 09 / 19 / 2025, p. 62 / 189 53 / 143

[0231] In some modalities, the pediatric patient has a body weight in a range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution.

[0232] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, such as about 0.8, 0.9 or about 1.0 to about 1.1, or about 1.2 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.9 mg / mL to about 1.1 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 1.0 mg / mL.

[0233] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution.

[0234] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, such as from about 0.3, 0.4 or about 0.5 to about 0.6, or about 0.7 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.4 mg / mL to about 0.6 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 0.5 mg / mL.

[0235] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0236] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. Petition 870250084429, dated 09 / 19 / 2025, p. 63 / 189 54 / 143

[0237] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, such as about 0.8, 0.9 or about 1.0 to about 1.1, or about 1.2 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.9 mg / mL to about 1.1 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 1.0 mg / mL.

[0238] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution.

[0239] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, such as about 0.3, 0.4 or about 0.5 to about 0.6, or about 0.7 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.4 mg / mL to about 0.6 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 0.5 mg / mL.

[0240] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0241] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution.

[0242] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution.

[0243] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, such as approximately 0.8, 0.9 or approximately 1.0 to approximately 1.1, or approximately 1.2 mg / mL. In some embodiments, the solution Petition 870250084429, dated 09 / 19 / 2025, p. 64 / 189 55 / 143 oral comprises upadacitinib at a concentration of approximately 0.9 mg / mL to approximately 1.1 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 1.0 mg / mL.

[0244] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution.

[0245] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution.

[0246] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, such as about 0.3, 0.4 or about 0.5 to about 0.6, or about 0.7 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.4 mg / mL to about 0.6 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 0.5 mg / mL.

[0247] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0248] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0249] In some embodiments, the pediatric patient has a body weight of about 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as a prolonged-release tablet.

[0250] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. Petition 870250084429, dated 09 / 19 / 2025, p. 65 / 189 56 / 143

[0251] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution.

[0252] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, such as about 0.8, 0.9 or about 1.0 to about 1.1, or about 1.2 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.9 mg / mL to about 1.1 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 1.0 mg / mL.

[0253] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution.

[0254] In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, such as about 0.3, 0.4 or about 0.5 to about 0.6, or about 0.7 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.4 mg / mL to about 0.6 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of 0.5 mg / mL.

[0255] In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0256] In some embodiments, the pediatric patient has a body weight of about 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as a prolonged-release tablet.

[0257] The maximum concentration achieved (Cmax) with the dosage mentioned above may vary depending on, for example, the dose, the patient's weight, and the individual patient's metabolism of upadacitinib. Petition 870250084429, dated 09 / 19 / 2025, p. 66 / 189 57 / 143

[0258] In some embodiments, when an immediate-release oral solution, as described in this document, is administered twice daily to the pediatric individual, a mean Cmax for upadacitinib is achieved in a range of about 20 to about 160 ng / mL.

[0259] In some embodiments, when administered twice daily at a dose of 3 or 4 mg each (3 or 4 mg 2x / day) to the pediatric individual, a mean Cmax for upadacitinib is achieved in a range of about 25 to about 50 ng / mL, such as about 25 to about 35, about 25 to about 33, about 25 to about 31, about 25 to about 29 or about 25 to about 27 ng / mL.

[0260] In some embodiments, when administered twice daily at a dose of 6 or 8 mg each (6 or 8 mg 2x / day) to the pediatric individual, a mean Cmax for upadacitinib is achieved in a range of about 40 to about 100 ng / mL, such as about 40 to about 95, about 40 to about 90, about 40 to about 85, about 40 to about 80, about 40 to about 75, about 40 to about 70, about 40 to about 65, about 40 to about 60, about 40 to about 55, about 40 to about 50, or about 40 to about 45 ng / mL.

[0261] In some embodiments, when a 15 mg extended-release tablet, as described herein, is administered once daily (15 mg 1x / day) to the pediatric individual, a mean Cmax for upadacitinib is achieved in a range of about 45 to about 50 ng / mL, such as about 45 to about 49, about 45 to about 48, about 45 to about 46 or about 45 to about 46 ng / mL.

[0262] In some embodiments, when a 30 mg extended-release tablet, as described herein, is administered once daily (30 mg 1x / day) to the pediatric individual, a mean Cmax for upadacitinib is achieved in a range of about 150 to about 160 ng / mL, such as about 152 to about 159, about 153 to about 158, about 154 to about 156 or about Petition 870250084429, dated 09 / 19 / 2025, p. 67 / 189 58 / 143 from 154 to approximately 155 ng / mL.

[0263] The mean 24-hour exposure achieved (AUC0-24) with the above-mentioned dosage may vary depending, for example, on the dose, the patient's weight, whether the patient was fed or fasted, and the patient's individual upadacitinib metabolism.

[0264] In some embodiments, when an immediate-release oral solution, as described herein, is administered twice daily to the pediatric individual, a mean AUC0-24 for upadacitinib is achieved in a range of about 200 to about 700 ng^h / mL.

[0265] In some embodiments, when administered twice daily at a dose of 3 or 4 mg each (3 or 4 mg 2x / day) to the pediatric individual, a mean AUC0-24 for upadacitinib is achieved in a range of approximately, such as approximately 220 to approximately 270 ng^h / mL, such as approximately 220 to approximately 265, approximately 220 to approximately 260, approximately 220 to approximately 255, approximately 220 to approximately 250, approximately 220 to approximately 245, approximately 220 to approximately 240, approximately 220 to approximately 235, approximately 220 to approximately 230, or approximately 220 to approximately 225 ng^h / mL.

[0266] In some embodiments, when administered twice daily at a dose of 6 or 8 mg each (6 or 8 mg 2x / day) to the pediatric individual, a mean AUC0-24 for upadacitinib is achieved in a range of about 340 to about 590 ng^h / mL, such as about 340 to about 580, about 340 to about 570, about 340 to about 560, about 340 to about 550, about 340 to about 540, about 340 to about 530, about 340 to about 520, about 340 to about 510, about 340 to about 500, about 340 to about 490, about 340 to about 480, from about 340 to about 470, from about 340 to about 460, from about 340 to about 450, from about 340 to about 440, from about 340 to about 430, from about 340 to about 420, from about 340 to about 410, from about 340 to about 400, from about 340 to about 390, from about 340 to about Petition 870250084429, dated 09 / 19 / 2025, page 68 / 189 59 / 143 of 380, of about 340 to about 370, of about 340 to about 360, of about 340 to about 350, or of about 340 to about 345 ng^h / mL. In some embodiments, when administered twice daily at a dose of 6 or 8 mg each (6 or 8 mg 2x / day) to the pediatric individual, a mean AUC0-24 for upadacitinib is achieved in a range of about 570 to about 590 ng^h / mL, such as about 570 to about 590, about 570 to about 588, about 570 to about 586, about 570 to about 584, about 570 to about 582 or about 570 to about 580 ng^h / mL.

[0267] In some embodiments, when a 15 mg extended-release tablet, as described herein, is administered once daily (15 mg 1x / day) to the pediatric individual, a mean AUC0-24 for upadacitinib is achieved in a range of about 45 to about 50 ng^h / mL, such as about 45 to about 49, about 46 to about 48, or about 47 to about 48 ng^h / mL.

[0268] In some embodiments, when a 30 mg extended-release tablet, as described herein, is administered once daily (30 mg 1x / day) to the pediatric individual, a mean AUC0-24 for upadacitinib is achieved in a range of about 650 to about 680 ng / mL, such as about 660 to about 670, or about 665 to about 670 ng^h / mL.

[0269] The disclosed methods generally involve administering upadacitinib orally to the patient daily for a period of time. In some embodiments, administration is continued at the same dose and dosing frequency over a treatment period. The duration of the treatment period may vary. For example, the treatment period may be at least 14 days, at least one month, 3 months, 4 months, 6 months, 9 months, 1 year, 2 years, 5 years, 10 years, 20 years, 50 years or more. In some embodiments, the treatment period is 12 weeks. In some embodiments, the treatment period is 156 weeks. In some embodiments, the treatment period is at least 156 weeks. V. Treatment of Pediatric Patients with Juvenile Idiopathic Arthritis Petition 870250084429, dated 09 / 19 / 2025, p. 69 / 189 60 / 143 Polyarticular

[0270] In some modalities, the pediatric patient has polyarticular juvenile idiopathic arthritis (pcJIA), including rheumatoid factor-positive or rheumatoid factor-negative polyarticular JIA, extended oligoarticular JIA, or systemic JIA with active arthritis and without active systemic features.

[0271] Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment in JIA, as they are believed to be the least toxic agent in children. They provide symptomatic relief but are not considered disease-modifying. Disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX) and sulfasalazine, are effective in JIA, while hydroxychloroquine, D-penicillamine, and auranofin are not. Most children respond to MTX therapy, which has acceptable toxicity, although remission is rare. To varying degrees, systemic corticosteroid use is frequent in all JIA conditions, but particularly for JIA it is less desirable due to many deleterious effects. Systemic and intra-articular corticosteroids are being used in JIA in conjunction with NSAIDs and DMARDs.Intra-articular (IA) corticosteroid injections are recommended in patients with JIA who have active arthritis, regardless of the use of additional concomitant therapy. IA steroids, however, are frequently used and often induce prolonged remission in children with oligoarticular JIA.

[0272] Many potent biological agents are now available for use in the treatment of JIA and are capable of inducing remission in JIA when used as monotherapy or in combination with MTX or other synthetic DMARDs. However, many patients still do not achieve a state of remission or low disease activity with these agents or lose response over time. Furthermore, given the potential safety concerns associated with the immunomodulatory effects of biological agents, and given the fact that all biological agents are administered by injection, Petition 870250084429, dated 09 / 19 / 2025, page 70 / 189 61 / 143 new oral treatment options with an improved benefit / risk profile are warranted for treating JIA. Consequently, it would be desirable to provide pediatric patients with an alternative therapy for the treatment of pcJIA.

[0273] JAK inhibition is known to inhibit the IL-6 pathway, and IL-6, in turn, is known to be involved in the pathogenesis of RA and juvenile idiopathic arthritis (JIA). See, for example, Ou et al. Clin Rheumatol. 2002, 21:52-6; Mangge et al. Arthritis Rheum. 1995, 38(2):211-20; and Mellins et al. Nat Rev Rheumatol. 2011, 7(7):416-26. In particular, inhibition of the JAK1 subtype blocks the signaling of many important pro-inflammatory cytokines, including interleukin (IL)-2, IL-6, IL-7, and IL-15, which are known contributors to inflammatory disorders. By modulating these pro-inflammatory cytokine pathways, upadacitinib offers the potential for the effective treatment of inflammatory or autoimmune disorders.Without intending to adhere to any particular theory, it is believed that, based on its differentiated selectivity profile for JAK inhibition, upadacitinib could demonstrate an improved benefit / risk profile compared to other less selective JAK inhibitors or other therapeutic strategies for patients with inflammatory diseases. In particular, upadacitinib is believed to provide therapeutic benefit in pcJIA.

[0274] In adults, the area under the plasma concentration curve (AUC) of upadacitinib over 0-24 hours (AUC0-24) at steady state was 362 and 720 ng^h / mL after multiple doses of 15 mg and 30 mg once daily (1x / day), respectively. Consequently, the pediatric doses that achieve such exposures are disclosed here as described above.

[0275] As disclosed herein, a prototype oral solution formulation was developed to allow for appropriate and flexible dosing in younger pediatric patients. Administration of two 6 mg doses of upadacitinib oral solution. Petition 870250084429, dated 09 / 19 / 2025, page 71 / 189 A 62 / 143 (1 mg / mL) dose administered 12 hours apart resulted in Cmax and AUC values ​​approximately 30% and 20% higher, respectively, compared to a single 15 mg once-daily dose of upadacitinib (used in the phase 3 RA studies) under fasting conditions; these results supported the selection of upadacitinib doses in pediatric subjects in the Example 1 study.

[0276] Consequently, in one aspect, a method of treating pcJIA in a pediatric patient is provided using pediatric dosing based on body weight, as disclosed above. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0277] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose is given twice daily as about 6 mL of the about 0.5 mg / mL solution.

[0278] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose Petition 870250084429, dated 09 / 19 / 2025, p. 72 / 189 63 / 143 is administered twice daily, as approximately 12 mL of a solution containing about 0.5 mg / mL.

[0279] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0280] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0281] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0282] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 8 mg of Petition 870250084429, dated 09 / 19 / 2025, p. 73 / 189 64 / 143 upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is delivered twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is delivered twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0283] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0284] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0285] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0286] In some modalities, the pediatric patient has a history of Petition 870250084429, dated 09 / 19 / 2025, p. 74 / 189 65 / 143 arthritis affecting at least 5 joints in the first 6 months of disease (for extended oligoarticular JIA: < 4 joints during the first 6 months of disease and > 4 joints thereafter), according to the criteria of the International League of Associations for Rheumatology (ILAR).

[0287] In some modalities, the pediatric patient does not have a diagnosis of enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (JPSA).

[0288] In some modalities, the pediatric patient has 5 or more active joints, defined as the presence of swollen joints (not due to deformity) or, in the absence of swelling, joints with limited range of motion (LOM) plus pain on movement and / or tenderness on palpation, with LOM present in at least three of the active joints.

[0289] In some modalities, the pediatric patient is receiving methotrexate. In such modalities, the patient must be on a stable dose of < 20 mg / m2 for at least 8 weeks before the start of administration.

[0290] In some modalities, the pediatric patient is receiving oral glucocorticoids. In such modalities, the patient must be on a stable dose (not exceeding 10 mg / day or 0.2 mg / kg / day, whichever is lower) for at least 1 week before initiation of administration.

[0291] In some modalities, the patient achieves one or more JIA ACR 30 / 50 / 70 / 90 / 100 pediatric responses, a change from baseline in JADAS10 / 27 / 71 responses, low disease activity, or remission according to JADAS-based criteria. In some modalities, the patient achieves one or more JIA ACR 30 / 50 / 70 / 90 / 100 pediatric responses at 12 weeks, 24 weeks, or 48 weeks.

[0292] In some modalities, the pediatric patient does not have continuous or active uveitis within 3 months prior to the start of treatment, active infection(s) Petition 870250084429, dated 09 / 19 / 2025, p. 75 / 189 66 / 143 of TB requiring treatment with parenteral anti-infectives, chronic recurrent infection and / or active viral infection, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), a positive beta-D-glucan result.

[0293] In some modalities, the pediatric patient was not treated with intra-articular or parenteral administration of corticosteroids in the 4 weeks prior to the start of administration.

[0294] In some modalities, the pediatric patient has no history of: any malignancy, except for successfully treated nonmelanoma skin cancer or localized carcinoma in situ of the cervix, recurrent or disseminated herpes zoster (even a single episode); disseminated herpes simplex (even a single episode); human immunodeficiency virus (HIV) infection; prior organ transplantation requiring ongoing immunosuppression, gastrointestinal perforation (except appendicitis or penetrating injury), diverticulitis, or significantly increased risk of gastrointestinal perforation; prior exposure to a JAK inhibitor.

[0295] In some modalities, the pediatric patient is not using known moderate or strong inhibitors (e.g., amiodarone, clarithromycin, fluconazole, ciprofloxacin, itraconazole, ketoconazole, quinidine, fluoxetine, and paroxetine) or inducers (e.g., carbamazepine, rifampicin, phenobarbital, and phenytoin) of drug-metabolizing enzymes.

[0296] In some modalities, the pediatric patient is not using biological treatment (etanercept, infliximab, adalimumab, abatacept, golimumab, tocilizumab, ustekinumab, certolizumab pegol, canakinumab, anakinra).

[0297] In some modalities, the pediatric patient is not using a JAK inhibitor (e.g., upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], ruxolitinib [Jakafi®], baricitinib [Olumiant®], peficitinib [Smyraf®], abrocitinib [PF04965842], or commercially available filgotinib). Petition 870250084429, dated 09 / 19 / 2025, page 76 / 189 67 / 143

[0298] In some modalities, the pediatric patient has moderate to severely active pcJIA.

[0299] In some modalities, the pediatric patient has shown an inadequate response to one or more DMARDs.

[0300] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. VI. Treatment of Pediatric Patients with Systemic Juvenile Idiopathic Arthritis

[0301] In some modalities, the pediatric patient has systemic juvenile idiopathic arthritis (SJIA), which may also be referred to as Still's disease or systemic juvenile rheumatoid arthritis. SJIA is officially a subset of juvenile idiopathic arthritis (JIA), although the pathophysiology is more consistent with an autoinflammatory disorder. SJIA affects not only the joints but other parts of the body, including the liver, lungs, and heart. The course of SJIA is highly variable, usually manifesting initially with a period of several months of fevers and skin rashes, with varying degrees of arthralgia and arthritis. Currently, there is no cure for SJIA, but remission is possible. Traditionally, a typical treatment goal for children with SJIA included relieving pain and controlling symptoms using nonsteroidal anti-inflammatory drugs (NSAIDs) and / or high doses of oral or IV corticosteroids.More recently, biological and non-biological disease-modifying antirheumatic drugs (DMARDs) have become available. However, it remains desirable in the art to provide pediatric patients with safe, well-tolerated, and effective alternative therapies of non-biological DMARDs for the treatment of IAS.

[0302] JAK inhibition is known to inhibit the IL-6 pathway, and IL-6, in turn, is known to be involved in the pathogenesis of RA and juvenile idiopathic arthritis (JIA). See, for example, Ou et al. Clin Rheumatol. 2002, 21:52-6; Mangge et al. Artrite Rheum. 1995, 38(2):211-20; and Mellins et al. Nat Rev Rheumatol. 2011, Petition 870250084429, dated 09 / 19 / 2025, p. 77 / 189 68 / 143 7(7):416-26. In particular, inhibition of the JAK1 subtype blocks the signaling of many important pro-inflammatory cytokines, including interleukin (IL)-2, IL-6, IL-7, and IL-15, which are known contributors to inflammatory disorders. By modulating these pro-inflammatory cytokine pathways, upadacitinib offers the potential for the effective treatment of inflammatory or autoimmune disorders. Without intending to be tied to any particular theory, it is believed that, based on its differentiated selectivity profile for JAK inhibition, upadacitinib could demonstrate an improved benefit / risk profile compared to other less selective JAK inhibitors or other therapeutic strategies for patients with inflammatory diseases. In particular, upadacitinib is believed to provide therapeutic benefit in SJIA.

[0303] Pediatric doses that achieve exposures consistent with efficacy in adult patients are disclosed in this document as described above (i.e., based on body weight). Consequently, in one aspect, a method of treating SJIA in a pediatric patient using pediatric dosing based on body weight, as disclosed above, is provided. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0304] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose Petition 870250084429, dated 09 / 19 / 2025, p. 78 / 189 69 / 143 is administered twice daily, as approximately 6 mL of a solution containing approximately 0.5 mg / mL.

[0305] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution.

[0306] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0307] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0308] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 6 mg of Petition 870250084429, dated 09 / 19 / 2025, p. 79 / 189 70 / 143 upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is delivered twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is delivered twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0309] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0310] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0311] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as a prolonged-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily. Petition 870250084429, dated 09 / 19 / 2025, pp. 80 / 189 71 / 143 (30 mg once daily) as a prolonged-release tablet.

[0312] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0313] In some modalities, the pediatric patient has moderate to severely active sJIA.

[0314] In some modalities, the pediatric patient has shown an inadequate response to one or more DMARDs.

[0315] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. VII. Treatment of Pediatric Patients with Atopic Dermatitis

[0316] In some modalities, the pediatric patient has atopic dermatitis (AD; also known as atopic eczema). AD is an inflammatory, pruritic, chronic or chronically relapsing skin disease. Common clinical features include erythema, edema, xerosis, erosions / excoriations, exudation and crusting, and lichenification, but vary according to the patient's age and the chronicity of the lesions. Pruritus is a characteristic of the condition that accounts for a large part of the disease burden borne by patients and their families (Williams, N. Engl. J. Med. 2005, 352(22):2314-24). AD is one of the most common skin diseases, affecting up to 20% of children. In approximately 70% of cases, AD begins in children under 5 years of age (Williams et al., Atopic dermatitis: the epidemiology, causes, and prevention of atopic eczema. Cambridge, United Kingdom: Cambridge University Press, 2000:41-59).Long-term oral treatment options are limited for patients with moderate to severe Alzheimer's disease who are recalcitrant to topical therapy; most... Petition 870250084429, dated 09 / 19 / 2025, page 81 / 189 72 / 143 of conventional oral immunosuppressive therapies are used off-indications, have limited efficacy data, and are not suitable for long-term treatment due to their safety profiles. Consequently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of AD.

[0317] Pediatric doses (i.e., based on body weight) achieving exposures consistent with efficacy in adult patients are disclosed in this document as described above and in Example 1 below. Consequently, in one aspect, a method of treating AD in a pediatric patient using pediatric dosing based on body weight, as disclosed above, is provided. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0318] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of AD in an adult patient.

[0319] In some embodiments, the pediatric patient is under twelve years of age and has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose is given twice daily as about 6 mL of the about 0.5 mg / mL solution. Petition 870250084429, dated 09 / 19 / 2025, p. 82 / 189 73 / 143

[0320] In some embodiments, the pediatric patient is under twelve years of age and has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution.

[0321] In some embodiments, the pediatric patient is under twelve years of age and has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0322] In some embodiments, the pediatric patient is under twelve years of age and has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution. Petition 870250084429, dated 09 / 19 / 2025, p. 83 / 189 74 / 143

[0323] In some embodiments, the pediatric patient is under twelve years of age and has a body weight of approximately 30 kg or more, the method comprising administering 6 mg of upadacitinib twice daily (6 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0324] In some embodiments, the pediatric patient is under twelve years of age and has a body weight of approximately 30 kg or more, the method comprising administering 8 mg of upadacitinib twice daily (8 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0325] In some embodiments, the pediatric patient is under twelve years of age and has a body weight of approximately 30 kg or more, the method comprising administering 12 mg of upadacitinib twice daily (12 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0326] In some embodiments, the pediatric patient is under twelve years of age and has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as a Petition 870250084429, dated 09 / 19 / 2025, p. 84 / 189 75 / 143 extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0327] In some embodiments, the pediatric patient is twelve years of age or older and has a body weight of less than about 40 kg, the method comprises administering 8 mg of upadacitinib twice daily (8 mg 2x / day) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0328] In some embodiments, the pediatric patient is twelve years of age or older and has a body weight of less than about 40 kg, the method comprises administering 15 mg of upadacitinib once daily (15 mg 1x / day) as a prolonged-release tablet. In some embodiments, the pediatric patient has a body weight of about 30 kg or more, the method comprises administering 30 mg of upadacitinib once daily (30 mg 1x / day) as a prolonged-release tablet.

[0329] In some modalities, the pediatric patient achieves one or more validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1, or an Eczema Area and Severity Index of at least 75% (EASI 75), 90% (EASI 90), or 100% (EASI 100). In some modalities, the pediatric patient achieves one or more validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1, or an Eczema Area and Severity Index of at least 75% (EASI 75), 90% (EASI 90), or 100% (EASI 100) is achieved in 8 Petition 870250084429, dated 09 / 19 / 2025, p. 85 / 189 76 / 143 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, 48 ​​weeks, or 52 weeks after the first daily administration. In some embodiments, the pediatric patient achieves an Eczema Area and Severity Index of 75 at 12 weeks after the first daily administration. In some embodiments, the pediatric patient achieves an Eczema Area and Severity Index of 90 at 12 weeks after the first daily administration. In some embodiments, the pediatric patient achieves an Eczema Area and Severity Index of 100 at 12 weeks after the first daily administration. In some embodiments, the pediatric patient achieves a score on the Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scale of 0 or 1 at 12 weeks after the first daily administration.In some modalities, the pediatric patient achieves a score on the Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scale of 0 at 12 weeks after the first daily administration. In some modalities, the pediatric patient achieves a score on the Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scale of 1 at 12 weeks after the first daily administration.

[0330] In some modalities, the pediatric patient has severe AD.

[0331] In some modalities, the pediatric patient has moderate to severely active pcJIA.

[0332] In some modalities, the pediatric patient presented an inadequate response to one or more TCS.

[0333] In some modalities, the pediatric patient has shown an inadequate response to one or more biological therapies. VIII. Treatment of Pediatric Patients with Juvenile Psoriatic Arthritis

[0334] In some modalities, the pediatric patient has juvenile psoriatic arthritis (JPsA). JPsA is a chronic systemic inflammatory disease classified as a subtype of spondyloarthritis (SpA) and characterized by the association of arthritis and psoriasis. The course of JPsA is generally characterized by flare-ups and remissions. If Petition 870250084429, dated 09 / 19 / 2025, page 86 / 189 If left untreated, patients with JPsA may experience persistent inflammation, progressive joint damage, disability, and reduced life expectancy. Initial treatment of musculoskeletal symptoms consists of nonsteroidal anti-inflammatory drugs (NSAIDs) and topical corticosteroid injections, while topical therapies are used for the initial treatment of psoriasis. For individuals who experience ineffectiveness or toxicity with these measures, systemic therapy with nonbiological disease-modifying antirheumatic drugs (nonbiological DMARDs) (e.g., methotrexate [MTX], leflunomide [LEF], sulfasalazine [SSZ]) and cyclosporine A, followed by tumor necrosis factor (TNF) therapy in individuals who do not respond adequately, is recommended. Other biological therapies (e.g., IL-12 / 23 or IL-17 inhibitors) are also recommended as alternatives to anti-TNF inhibitors in individuals with selected PsA.See, for example, Gossec et al., Ann Rheum Dis. (2016) 75: 499-510; Coates et al., Arthritis Rheumatol. (2016) 68: 1060-71. However, despite the beneficial results achieved with currently available biological agents, approximately 40% of patients do not show at least a 20% improvement in American College of Rheumatology (ACR) scores, and only 58% to 61% of PsA patients who receive them are able to achieve clinical remission after 1 year of treatment, with only approximately 43% achieving sustained remission for at least 1 year. See, for example, Gossec et al., Ann Rheum Dis. (2016) 75: 499-510; Alamanos et al., J Rheumatol. (2003) 30: 2641-2644; Savolainen et al., J Rheumatol. (2003) 30: 2460-8; Sandborn, DigDis. (2010) 28: 536-42; Saber et al., Arthritis Res Therapy (2010) 12: R94; Perrotta et al., J Rheumatol. (2016) 43: 350-5.

[0335] Thus, there continues to be a clear medical need for additional therapeutic options for the treatment of juvenile psoriatic arthritis (JPsA). Conse Petition 870250084429, dated 09 / 19 / 2025, p. 87 / 189 78 / 143 Currently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of JPsA.

[0336] Pediatric doses (i.e., based on body weight) achieving exposures consistent with efficacy in adult patients are disclosed in this document as described above and in Example 1 below. Consequently, in one aspect, a method of treating JPsA in a pediatric patient using pediatric dosing based on body weight, as disclosed above, is provided. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0337] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of JPsA in an adult patient.

[0338] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose is given twice daily as about 6 mL of the about 0.5 mg / mL solution.

[0339] In some modalities, the pediatric patient has a body weight in a range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as a solution Petition 870250084429, dated 09 / 19 / 2025, pp. 88 / 189 79 / 143 oral. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is delivered twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is delivered twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0340] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0341] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0342] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the solution. Petition 870250084429, dated 09 / 19 / 2025, p. 89 / 189 80 / 143 approximately 1 mg / mL. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0343] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0344] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0345] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0346] In some modalities, the pediatric patient has a body weight Petition 870250084429, dated 09 / 19 / 2025, pp. 90 / 189 81 / 143 weighing approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0347] In some modalities, the pediatric patient has moderately to severely active JPsA.

[0348] In some modalities, the pediatric patient presented an inadequate response to one or more DMARDs.

[0349] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. IX. Treatment of Pediatric Patients with Juvenile Ankylosing Spondylitis

[0350] In some modalities, the pediatric patient has juvenile ankylosing spondylitis (JAS). Juvenile ankylosing spondylitis is a chronic inflammatory rheumatic disease that primarily affects the axial skeleton, characterized by chronic low back pain (including nocturnal low back pain), morning stiffness, enthesitis, peripheral arthritis, and extra-articular manifestations.

[0351] Due to the long-term debilitating nature of AS, irreversible structural damage often occurs, negatively impacting patients' lives. There is no cure for AS; therefore, the primary goal of treatment is to maximize patients' quality of life by controlling the signs and symptoms of the disease, preventing structural damage, and maintaining physical function, preferably achieving sustained clinical remission or, at a minimum, low disease activity. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for AS, followed by biological disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor (TNF) inhibitors or interleukin-17 (IL-17) inhibitors, in patients who do not respond sufficiently to NSAIDs. Petition 870250084429, dated 09 / 19 / 2025, page 91 / 189 82 / 143 TNF inhibitors and IL-17 inhibitors are effective in some patients with AS, but there are still patients for whom none of these approved therapies address their individual treatment goals. AS is a difficult disease to treat, as demonstrated by the low efficacy achieved with the IL-6 inhibitors tocilizumab and sarilumab, as well as the IL-12 / 23 inhibitor ustekinumab and the T-cell blockade inhibitor abatacept. See, for example, Sieper et al., Ann. Rheum. Dis. 2014, 73:95-100, Sieper et al., Ann. Rheum. Dis. 2015, 74:1051-1057; Deodhar et al., Arthritis and Rheumatology 2019, 71:258-270, and Song et al., Ann. Rheum. Dis. 2011, 70:1108-1110.

[0352] Thus, there continues to be a clear medical need for additional therapeutic options for the treatment of juvenile ankylosing spondylitis (JAS). Consequently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of AS.

[0353] Pediatric doses (i.e., based on body weight) achieving exposures consistent with efficacy in adult patients are disclosed in this document as described above and in Example 1 below. Consequently, in one aspect, a method of treating JAS in a pediatric patient using pediatric dosing based on body weight, as disclosed above, is provided. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0354] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of JAS in an adult patient.

[0355] In some modalities, the pediatric patient has body weight Petition 870250084429, dated 09 / 19 / 2025, p. 92 / 189 83 / 143 in a range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose is given twice daily as about 6 mL of the approximately 0.5 mg / mL solution.

[0356] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution.

[0357] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0358] In some modalities, the pediatric patient has a body weight in a range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as a solution Petition 870250084429, dated 09 / 19 / 2025, p. 93 / 189 84 / 143 oral. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is delivered twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is delivered twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0359] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0360] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0361] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration Petition 870250084429, dated 09 / 19 / 2025, p. 94 / 189 85 / 143 of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily, as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0362] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0363] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0364] In some modalities, the pediatric patient has moderately to severely active JAS.

[0365] In some modalities, the pediatric patient has shown an inadequate response to one or more DMARDs.

[0366] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. X. Treatment of Pediatric Patients with Non-Radiographic Axial Spondyloarthritis

[0367] In some modalities, the pediatric patient has non-radiographic axial spondyloarthritis (nr-axSpA). Nr-axSpA is a chronic inflammatory rheumatic disease that primarily affects the axial skeleton, characterized by chronic low back pain (including nocturnal low back pain), morning stiffness, enthesitis, peripheral arthritis, and ma Petition 870250084429, dated 09 / 19 / 2025, page 95 / 189 86 / 143 extra-articular manifestations. Nr-axSpA is the early form of ankylosing spondylitis (AS) and shares many of the same characteristics.

[0368] Due to the long-term debilitating nature of nr-axSpA, irreversible structural damage often occurs, negatively impacting patients' lives. There is no cure for nr-axSpA; therefore, the primary goal of treatment is to maximize patients' quality of life by controlling the signs and symptoms of the disease, preventing structural damage, and maintaining physical function, preferably achieving sustained clinical remission or, at a minimum, low disease activity. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for AS, followed by biological disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor (TNF) inhibitors or interleukin-17 (IL-17) inhibitors, in patients who do not respond sufficiently to NSAIDs.TNF inhibitors and IL-17 inhibitors are effective in some patients with AS, but there are still patients for whom none of these approved therapies address their individual treatment goals. AS is a difficult disease to treat, as demonstrated by the low efficacy achieved with the IL-6 inhibitors tocilizumab and sarilumab, as well as the IL-12 / 23 inhibitor ustekinumab and the T-cell blockade inhibitor abatacept. See, for example, Sieper et al., Ann. Rheum. Dis. 2014, 73:95-100, Sieper et al., Ann. Rheum. Dis. 2015, 74:1051-1057; Deodhar et al., Arthritis and Rheumatology 2019, 71:258-270, and Song et al., Ann. Rheum. Dis. 2011, 70:1108-1110. Consequently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of nraxSpA.

[0369] Pediatric doses (i.e., based on body weight) achieving exposures consistent with efficacy in adult patients are disclosed in this document as described above and in Example 1 below. Consequently, in a Petition 870250084429, dated 09 / 19 / 2025, page 96 / 189 In aspect 87 / 143, a method of treating nr-axSpA in a pediatric patient using pediatric dosing based on body weight is provided, as disclosed above. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0370] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of nraxSpA in an adult patient.

[0371] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose is given twice daily as about 6 mL of the about 0.5 mg / mL solution.

[0372] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution.

[0373] In some modalities, the pediatric patient has body weight Petition 870250084429, dated 09 / 19 / 2025, p. 97 / 189 88 / 143 in a range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0374] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0375] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0376] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately Petition 870250084429, dated 09 / 19 / 2025, pp. 98 / 189 89 / 143 of 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0377] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0378] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0379] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0380] In some modalities, the pediatric patient has moderate to severely active nr-axSpA. Petition 870250084429, dated 09 / 19 / 2025, page 99 / 189 90 / 143

[0381] In some modalities, the pediatric patient presented an inadequate response to one or more DMARDs.

[0382] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. XI. Treatment of Pediatric Patients with Hidradenitis Suppurativa

[0383] In some modalities, the pediatric patient has hidradenitis suppurativa (HS). HS refers to a debilitating skin disorder of the apocrine glands (sweat glands found in certain parts of the body) and hair follicles in which swollen, painful, and chronically inflamed lesions or nodules develop. HS is confined to areas of the body containing apocrine glands, such as the armpits, nipple areola, groin, perineum, circumanal and periumbilical regions. It is speculated that immunological abnormalities of the hair follicle play a role in the etiology of this disease. HS is a recurrent or chronic inflammatory condition that particularly affects young adults, with a mean age of onset of 23 years. This poorly understood disease is believed to be underreported by those who suffer from it, but it is estimated to affect approximately 1% of the general population in the West, with women being affected 2 to 5 times more commonly than men (Naldi, L. Epidemiology).In: Hidradenitis Suppurativa; Jemec et al., ed; Heidelberg: Springer. 2006).

[0384] HS is characterized by recurrent inflamed nodules, abscesses, and fistulas and occurs when the apocrine gland outlets become blocked by perspiration or are unable to drain normally due to incomplete gland development. Secretions trapped in the glands force perspiration and bacteria into the surrounding tissue, causing subcutaneous hardening, inflammation, and infection. HS lesions (i.e., nodules, abscesses, and sinuses) are painful and may have a foul odor with purulent discharge. This constellation of signs and symptoms results in substantial disability and social stigma for patients and a Petition 870250084429, dated 09 / 19 / 2025, pp. 100 / 189 91 / 143 profound impact on quality of life.

[0385] Current therapies for moderate to severe HS include short- or long-term oral or topical antibiotics, retinoids, intralesional steroids, oral steroids, immunosuppressive agents such as cyclosporine or methotrexate, radiation, laser therapy, and the tumor necrosis factor (TNF-α) antagonist adalimumab. However, adalimumab is the only approved treatment for HS, and other TNF antagonists, such as etanercept, have failed to show improvement in HS over a 24-week treatment period (Adams et al., Arch Dermatol. 146(5): 501-504, 2010). Given the limited success of treatments for HS and the debilitating nature of this disease, there is an urgent need for effective treatment. Consequently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of HS.

[0386] Pediatric doses (i.e., based on body weight) achieving exposures consistent with efficacy in adult patients are disclosed in this document as described above and in Example 1 below. Consequently, in one aspect, a method of treating HS in a pediatric patient using pediatric dosing based on body weight, as disclosed above, is provided. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0387] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of HS in an adult patient.

[0388] In some modalities, the pediatric patient has a body weight in a range of about 10 to less than about 20 kg, the method comprising Petition 870250084429, dated 09 / 19 / 2025, pp. 101 / 189 92 / 143 administer 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 3 mg dose is given twice daily as approximately 3 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 3 mg dose is given twice daily as approximately 6 mL of the approximately 0.5 mg / mL solution.

[0389] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution.

[0390] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0391] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily, as about Petition 870250084429, dated 09 / 19 / 2025, p. 102 / 189 93 / 143 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0392] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0393] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0394] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution. Petition 870250084429, dated 09 / 19 / 2025, p. 103 / 189 94 / 143

[0395] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0396] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has moderate to severe HS.

[0397] In some modalities, the pediatric patient has shown an inadequate response to one or more DMARDs.

[0398] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. XII. Treatment of Pediatric Patients with Systemic Lupus Erythematosus

[0399] In some modalities, the pediatric patient has systemic lupus erythematosus (SLE). SLE is an autoimmune disease distinguished by antibodies against nuclear and cytoplasmic antigens, multisystemic inflammation, proteinaceous clinical manifestations, and a relapsing-remitting course. SLE causes widespread inflammation and tissue damage in affected organs, which may include joints, skin, brain, lungs, kidneys, and blood vessels. Symptoms of SLE vary depending on the organs affected, but may include fatigue, skin rashes, fever, and joint pain or swelling.

[0400] Currently, there is no cure for SLE, and existing therapies focus on Petition 870250084429, dated 09 / 19 / 2025, pp. 104 / 189 95 / 143 improve quality of life by controlling symptoms and minimizing flare-ups, primarily with the use of immunosuppressive drugs such as hydroxychloroquine and corticosteroids, and immunomodulators such as belimumab and anifrolumab. Despite these treatments, significant unmet therapeutic needs remain for patients with SLE. Consequently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of SLE.

[0401] Pediatric doses (i.e., based on body weight) achieving exposures consistent with efficacy in adult patients are disclosed in this document as described above and in Example 1 below. Consequently, in one aspect, a method of treating SLE in a pediatric patient using pediatric dosing based on body weight, as disclosed above, is provided. The method generally comprises administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0402] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of SLE in an adult patient.

[0403] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose Petition 870250084429, dated 09 / 19 / 2025, pp. 105 / 189 96 / 143 is administered twice daily, as approximately 6 mL of a solution containing about 0.5 mg / mL.

[0404] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution.

[0405] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0406] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0407] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 6 mg of Petition 870250084429, dated 09 / 19 / 2025, pp. 106 / 189 97 / 143 upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is delivered twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is delivered twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0408] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0409] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0410] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as a prolonged-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily. Petition 870250084429, dated 09 / 19 / 2025, pp. 107 / 189 98 / 143 (30 mg once daily) as an extended-release tablet.

[0411] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0412] In some modalities, the pediatric patient has moderate to severely active SLE.

[0413] In some modalities, the pediatric patient has shown an inadequate response to one or more DMARDs.

[0414] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. XIII. Treatment of Pediatric Patients with Ulcerative Colitis

[0415] In some modalities, the pediatric patient has ulcerative colitis (UC). UC is one of the two primary forms of idiopathic inflammatory bowel disease (IBD). UC is a chronic relapsing inflammatory disease of the large intestine, characterized by inflammation and ulceration primarily of the intestinal mucosal layers and occasionally the submucosa. The main clinical symptoms of UC include bloody diarrhea associated with rectal urgency and tenesmus. The clinical course is marked by exacerbation and remission. Despite the treatment options available for patients with UC, significant unmet therapeutic needs remain. Consequently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of UC.

[0416] Pediatric doses that achieve exposures consistent with efficacy in adult patients are disclosed in this document as described above (or Petition 870250084429, dated 09 / 19 / 2025, pp. 108 / 189 99 / 143, that is, based on body weight). Consequently, in one aspect, a method of treating UC in a pediatric patient is provided using pediatric dosing based on body weight, as disclosed above. The method involves treating the pediatric patient suffering from UC by administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dosage form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight.

[0417] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of UC in an adult patient.

[0418] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose is given twice daily as about 6 mL of the about 0.5 mg / mL solution.

[0419] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution. Petition 870250084429, dated 09 / 19 / 2025, pp. 109 / 189 100 / 143

[0420] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution.

[0421] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0422] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0423] In some modalities, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some Petition 870250084429, dated 09 / 19 / 2025, pp. 110 / 189 In 101 / 143 embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is provided twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is provided twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0424] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0425] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0426] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has moderately to severely active UC. Petition 870250084429, dated 09 / 19 / 2025, pp. 111 / 189 102 / 143

[0427] In some modalities, the pediatric patient presented an inadequate response to one or more DMARDs.

[0428] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. XIV. Treatment of Pediatric Patients with Crohn's Disease

[0429] In some modalities, the pediatric patient has Crohn's disease (CD). CD is one of the two primary forms of idiopathic inflammatory bowel disease (IBD). CD is characterized by significant morbidity, including abdominal pain, diarrhea, weight loss / malnutrition, fatigue, and a progressive nature that leads to complications such as fistulas, strictures, and abscesses. Furthermore, approximately 80% of patients diagnosed with CD will require at least one disease-related surgery at some point (Munkholm P, Langholz E, Davidsen M, et al. Gastroenterology. 1993, 105(6):171-623). Despite the treatment options available for patients with CD, significant unmet therapeutic needs remain. Consequently, it is desirable in the art to provide pediatric patients with safe, well-tolerated, and effective therapies for the treatment of CD.

[0430] Pediatric doses that achieve exposures consistent with efficacy in adult patients are disclosed in this document as described above (i.e., based on body weight). Consequently, in one aspect, a method of treating UC in a pediatric patient using pediatric dosing based on body weight, as disclosed above, is provided. The method involves treating the pediatric patient suffering from UC by administering upadacitinib to the pediatric patient as a stable oral pharmaceutical formulation or a prolonged-release tablet. The amount of upadacitinib administered, the oral dose form, and the dosing frequency (e.g., once or twice daily) will vary based on the patient's weight. Petition 870250084429, dated 09 / 19 / 2025, pp. 112 / 189 103 / 143

[0431] In some modalities, pediatric dosing based on body weight provides exposures consistent with efficacy for the treatment of UC in an adult patient.

[0432] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 3 mg of upadacitinib twice daily (3 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 3 mg dose is given twice daily as about 3 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 3 mg dose is given twice daily as about 6 mL of the about 0.5 mg / mL solution.

[0433] In some embodiments, the pediatric patient has a body weight in the range of about 10 to less than about 20 kg, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 6 mg dose is given twice daily as about 6 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 6 mg dose is given twice daily as about 12 mL of the about 0.5 mg / mL solution.

[0434] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 4 mg of upadacitinib twice daily (4 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 4 mg dose is given twice daily as about 4 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 4 mg dose is given twice daily as about 8 mL of the about 0.5 mg / mL solution. Petition 870250084429, dated 09 / 19 / 2025, pp. 113 / 189 104 / 143

[0435] In some embodiments, the pediatric patient has a body weight in the range of about 20 to less than about 30 kg, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 1 mg / mL, and the 8 mg dose is given twice daily as about 8 mL of the about 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL, and the 8 mg dose is given twice daily as about 16 mL of the about 0.5 mg / mL solution.

[0436] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 6 mg of upadacitinib twice daily (6 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 6 mg dose is given twice daily as approximately 6 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 6 mg dose is given twice daily as approximately 12 mL of the approximately 0.5 mg / mL solution.

[0437] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 8 mg of upadacitinib twice daily (8 mg BID) as an oral solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 8 mg dose is given twice daily as approximately 8 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 8 mg dose is given twice daily as approximately 16 mL of the approximately 0.5 mg / mL solution.

[0438] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising the administration of 12 mg of upadacitinib twice daily (12 mg BID) as an oral solution. In some embodiments, Petition 870250084429, dated 09 / 19 / 2025, pp. 114 / 189 105 / 143 The oral solution comprises upadacitinib at a concentration of approximately 1 mg / mL, and the 12 mg dose is given twice daily as approximately 12 mL of the approximately 1 mg / mL solution. In some embodiments, the oral solution comprises upadacitinib at a concentration of approximately 0.5 mg / mL, and the 12 mg dose is given twice daily as approximately 24 mL of the approximately 0.5 mg / mL solution.

[0439] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0440] In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 15 mg of upadacitinib once daily (15 mg 1x / day) as an extended-release tablet. In some embodiments, the pediatric patient has a body weight of approximately 30 kg or more, the method comprising administering 30 mg of upadacitinib once daily (30 mg 1x / day) as an extended-release tablet.

[0441] In some modalities, the pediatric patient has moderately to severely active CD.

[0442] In some modalities, the pediatric patient presented an inadequate response to one or more DMARDs.

[0443] In some modalities, the pediatric patient presented an inadequate response to one or more TNF blockers. Exemplification Example 1: Evaluation of the Pharmacokinetics and Safety of Upadacitinib in Pediatric Individuals with Polyarticular Juvenile Idiopathic Arthritis Investigation plan Petition 870250084429, dated 09 / 19 / 2025, pp. 115 / 189 106 / 143

[0444] This was an open-label, Phase 1, multiple-dose study consisting of three parts in approximately 124 pediatric subjects aged 2 to less than 18 years with pcJIA. A study scheme is shown in Figure 1. Part 1 was a multiple-dose, open-label, multiple-dose cohort study. Two sequential ascending multiple-dose levels (low dose and high dose levels) were evaluated in the 12 to < 18 year age range (Group 1), and one dose level (low dose) was evaluated in the two younger age ranges (Group 2: 6 to < 12 years, and Group 3: 2 to < 6 years). Low-dose and high-dose cohorts in age range 1 enrolled 9 subjects each. Low-dose cohorts in age ranges 2 and 3 enrolled approximately 18 participants each.

[0445] The dose of upadacitinib was administered based on the individual's body weight, according to three body weight categories defined by dose level. The study involved at least 10 individuals weighing less than 30 kg. Participant recruitment was conducted using an age-based staggered approach. Participants who completed Part 1 and were benefiting from the study medication, without ongoing adverse events of special interest or serious adverse events, based on the investigator's clinical judgment and with the individual / family's consent, had the option to enroll in Part 2 to receive upadacitinib on an open-label basis. Part 2 was a long-term open-label extension to evaluate the long-term safety and tolerability of upadacitinib. Participants in Part 2 received upadacitinib on an open-label basis at the equivalent of the Low Dose level by body weight category.In Week 156, if the investigator considered that the participant was still benefiting from the treatment, there was the option to continue the treatment until the end of the study. Part 3 was an additional safety cohort. This additional safety cohort, involving approximately 70 individuals of all age ranges (2 to < 18 years), was added to assess safety and... Petition 870250084429, dated 09 / 19 / 2025, pp. 116 / 189 107 / 143 long-term tolerability of upadacitinib without intensive pharmacokinetic sampling. Part 3 was open to age groups in which Part 1 enrollment had been completed. Individuals in Part 3 received open-label upadacitinib at the equivalent of the Low Dose level by body weight category and, after screening and baseline assessment visits, followed a visit schedule identical to that of Part 2 participants, without intensive pharmacokinetic sampling. Doses were adjusted during the study for any of the body weight categories after review of the results of individuals who completed Part 1 of the study. Eligibility criteria • Male or female individuals, aged between 2 and under 18 years, and with a total body weight of 10 kg or more at the time of screening. • To be diagnosed with pcJIA (polyarticular rheumatoid factor-positive or rheumatoid factor-negative JIA, extended oligoarticular JIA, or systemic JIA with active arthritis and without active systemic features) with a history of arthritis affecting at least 5 joints in the first 6 months of disease (for extended oligoarticular JIA: < 4 joints during the first 6 months of disease and > 4 joints thereafter), according to the criteria of the International League of Rheumatology Associations (ILAR). • The individual must not have a diagnosis of enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (JPSA). • Must have 5 or more active joints at the time of screening, defined as the presence of swollen joints (not due to deformity) or, in the absence of swelling, joints with limited range of motion (LOM) plus pain on movement and / or tenderness to palpation, with LOM present in at least three of the active joints. • If you are receiving methotrexate (MTX), you must have been taking MTX for at least 12 weeks immediately before and including Day 1 of the Study at a dose of... Petition 870250084429, dated 09 / 19 / 2025, pp. 117 / 189 108 / 143 stable < 20 mg / m2 for at least 8 weeks prior to and including Day 1 of the Study; in addition, individuals should take folic acid or folinic acid according to the local standard of care. • If you are using oral glucocorticoids, you must have taken oral glucocorticoids at a stable dose (not exceeding 10 mg / day or 0.2 mg / kg / day, whichever is lower) for at least 1 week prior to and including Day 1 of the Study. • No prior exposure to JAK inhibitors. • No active or ongoing uveitis within 3 months prior to Day 1 of the Study. • The individual had not been treated with intra-articular or parenteral administration of corticosteroids in the 4 weeks prior to Day 1 of the study. • Must not have a history of any malignancy, except for successfully treated non-melanoma skin cancer or carcinoma in situ of the cervix. • Must not have a history of clinically significant drug or alcohol abuse (as determined by the investigator) in the past 6 months. • Must not have a history of allergic reaction or significant sensitivity to the constituents of the study drug (and its excipients) and / or to other products in the same class. • No current or past history of infection, including: • No history of recurrent or disseminated herpes zoster (even a single episode); • No history of disseminated herpes simplex (even a single episode); • Absence of infection with the human immunodeficiency virus (HIV); • The individual must not have active TB or meet the TB exclusion criteria (specific requirements for TB testing are provided in the Operations Manual); • Must not have active infection(s) requiring treatment with Petition 870250084429, dated 09 / 19 / 2025, pp. 118 / 189 109 / 143 parenteral anti-infectives in the 30 days prior or oral anti-infectives in the 14 days prior to Day 1 of the Study; • Must not have an active, chronic, or recurrent infection that, based on the investigator's clinical assessment, renders the individual an unsuitable candidate for the study; • Must not have any active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as: HBV: being positive (+) for hepatitis B surface antigen (HBsAg) or sensitivity detected in the HBV DNA CRP qualitative test for individuals positive (+) for hepatitis B core antibody (HBcAb); HCV: having detectable HCV ribonucleic acid (RNA) in any individual with anti-HCV antibody (HCV Ab). • The individual must not have previously received an organ transplant that requires ongoing immunosuppression. • Must not have a history of gastrointestinal perforation (except appendicitis or penetrating injury), diverticulitis, or a significantly increased risk of gastrointestinal perforation according to the investigator's judgment. • You must not have any condition that could interfere with the absorption of the medication, including, but not limited to, short bowel syndrome. • The patient must not have recently used known moderate or strong inhibitors (e.g., amiodarone, clarithromycin, fluconazole, ciprofloxacin, itraconazole, ketoconazole, quinidine, fluoxetine, and paroxetine) or inducers (e.g., carbamazepine, rifampicin, phenobarbital, and phenytoin) of drug-metabolizing enzymes within 30 days prior to the first dose of the study drug until the end of Part 1 of the study. The patient must not have used systemic inhibitors or strong inducers of the cytochrome P450 3A (CYP3A) isoform subfamily from the beginning of Part 2 or Part 3 of the study until the conclusion of the study. Prohibited therapies and medications Petition 870250084429, dated 09 / 19 / 2025, pp. 119 / 189 110 / 143 [ 0446] In addition to the medications listed in the eligibility criteria, the following were NOT permitted: Prior use of the following biologic treatments must have been discontinued before Day 1 of the study (etanercept, 4 weeks; infliximab, adalimumab, or abatacept, 8 weeks; golimumab, 10 weeks; tocilizumab, ustekinumab, and certolizumab pegol, 12 weeks; canakinumab, 10 weeks; anakinra, 1 week) and is also prohibited during the study. Note: If adequate documentation of undetectable drug levels measured by a commercially available assay exists for any of the approved biologics listed above, there is no minimum elimination before baseline. Immunosuppressive medications must have been discontinued at least 30 days or 5 half-lives before administration of the study medication until the end of the study. Current known use of known moderate or strong inhibitors (e.g., amiodarone, clarithromycin, fluconazole, ciprofloxacin, itraconazole, ketoconazole, quinidine, fluoxetine, and paroxetine) or inducers (e.g., carbamazepine, rifampicin, phenobarbital, and phenytoin) of drug-metabolizing enzymes within 30 days before the first dose of the study drug and until the end of Part 1 of the study. Systemic use of known strong inhibitors or inducers of CYP3A from the beginning of Part 2 or Part 3 until the end of the study. Live vaccines were not permitted during Part 1 of study participation. If the individual and investigator choose to administer live vaccines, these vaccinations should be completed, when possible (as per the local labeling), at least 4 weeks (8 weeks in Japan) before the first dose of the study medication, with appropriate precautions. Although not mandated by the protocol, vaccines recommended by local guidelines should be considered. If a live vaccine needs to be administered during Part 2 or Part 3 of study participation... Petition 870250084429, dated 09 / 19 / 2025, pp. 120 / 189 111 / 143 study, the study medication should be continued for at least 4 weeks (8 weeks in Japan) before vaccination and at least 4 weeks (8 weeks in Japan) after vaccination. Subsequently, the study medication may be resumed at the investigator's discretion with appropriate precautions. Experimental drugs must have been discontinued within 30 days or 5 half-lives of the drug (whichever is greater) before the first dose of the study drug. Investigational drugs are also prohibited during the study. JAK inhibitors (e.g., upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], ruxolitinib [Jakafi®], baricitinib [Olumiant®], peficitinib [Smyraf®], abrocitinib [PF-04965842], and filgotinib) were prohibited medications during the study.

[0447] Concomitant medications / therapy were permitted: Stable doses of nonsteroidal anti-inflammatory drugs (NSAIDs) Stable doses of low-dose glucocorticoids (< 0.2 mg / kg / day of prednisone; maximum daily dose, 10 mg) Steady-state doses of methotrexate ([MTX]; < 20 mg / m2 of body surface area / week) Study drug and treatment duration

[0448] The study drug was upadacitinib in the following formats and doses: 7.5 mg oral tablet; 15 mg oral tablet; 30 mg oral tablet; 1 mg / mL oral solution; 0.5 mg / mL oral solution. In Part 1, the dose was administered according to three body weight categories. Subjects were classified based on age range, and the dose administered for seven consecutive days will be based on three different body weight categories at the dose level shown in Table 2. The doses evaluated in this study are expected to provide ex Petition 870250084429, dated 09 / 19 / 2025, pp. 121 / 189 112 / 143 comparable plasma levels of upadacitinib in each body weight category to those provided by 15 mg once daily and 30 mg once daily using the extended-release formulation in adult subjects with RA. Doses were selected based on population pharmacokinetic analysis of upadacitinib in healthy adults and in adult subjects with RA and pharmacokinetic simulations in the different body weight categories, assuming allometric (weight-based) scaling of upadacitinib pharmacokinetic parameters (volume of distribution and clearance parameters).

[0449] The doses selected for this study represent the difference in oral bioavailability between the extended-release tablet formulation and the oral solution. Based on population pharmacokinetic analyses from Phase 1 to 3 studies, the mean plasma exposures of upadacitinib (median, with a 90% prediction interval) over a dosing range are 15.1 ng / mL (8.96 ng / mL to 32.7 ng / mL) for 15 mg once daily and 30.0 ng / mL (18.1 ng / mL to 63.8 ng / mL) for 30 mg once daily using the extended-release formulation in adult patients with RA; similar exposures were predicted to be achieved in pediatric patients at the low and high doses, respectively, within each body weight category based on pharmacokinetic simulations (Table 2). Doses were adjusted during the study for any of the body weight categories after reviewing the results of individuals who completed Part 1. Table 2. Upadacitinib Dosage by Body Weight Category and Level of Dose Dosage Level Body Weight Category* 10 to <20 kg 20 to <30 kg >30 kg Low Dose 3 mg BID Oral Solution 4 mg BID Oral Solution 15 mg QD Tablet (or 6 mg oral solution BID if the tablet cannot be swallowed) High Dose 6 mg BID Oral Solution 8 mg BID Oral Solution 30 mg QD Tablet Petition 870250084429, dated 09 / 19 / 2025, pp. 122 / 189 113 / 143 (or 12 mg of oral solution twice daily if it is not possible to swallow the tablet) 2X / day = twice a day; 1x / day = once a day

[0450] Individuals in Part 2 received open-label upadacitinib at the low dose level described in Table 2. At Week 156, if the investigator believed that the individual was still benefiting from treatment, they had the option to continue treatment at the equivalent of the Low Dose level by body weight category until the end of the study. Dose Adjustment Criteria

[0451] For each individual, the upadacitinib dose in Part 1 was based on the individual’s body weight at Screening and assigned study cohort. When preliminary pharmacokinetic and clinical data (after intensive Day 7 Part 1 pharmacokinetic sampling) from at least 4 participants were available in a cohort, these data were used to adjust doses, if necessary, for individuals who were enrolled (including participants in Parts 2 and 3) and for individuals who were subsequently enrolled. Additional criteria were considered to make dose adjustment decisions for Part 1, to ensure safe and effective exposures.

[0452] Individuals receiving upadacitinib in Part 2 continued to receive the same dose until their next scheduled visit (unless a previous dose adjustment was deemed necessary by the investigator). At their next scheduled visit, individuals in Part 2 received upadacitinib according to the dosing regimen (Table 2) for the remainder of the study. Individuals weighing > 30 kg had the option of receiving upadacitinib oral solution if they were unable to swallow the tablet (see Table 2). For individuals in Part 2 who underwent dose adjustments, blood samples for upadacitinib pharmacokinetic analysis were collected before dosing and 1 hour and 2 hours after dosing from individuals at an unscheduled visit that was 4 to 6 weeks later. Petition 870250084429, dated 09 / 19 / 2025, pp. 123 / 189 114 / 143 after the individual's dose adjustment visit. The time of the last two doses administered before the pre-dose trough pharmacokinetic sample and the time of blood sample collection were recorded to the nearest minute. During the same unscheduled visit, blood samples for clinical laboratory tests were also collected.

[0453] Individuals in Parts 2 and 3 received doses according to the Low Dose level by body weight category (Table 2) or as determined based on data available in Part 1. A change in the individual's body weight category was determined by the investigator at any of the study visits in Parts 2 and 3. A pharmacokinetic blood sample was collected from individuals in Parts 2 and 3 when the dose was modified due to the change in the individuals' body weight. Study objectives and outcomes Part 1:

[0454] To evaluate the pharmacokinetics, safety, and tolerability of multiple doses of upadacitinib in pediatric subjects with pcJIA. To evaluate the palatability of upadacitinib oral solution in pediatric subjects. To evaluate the descriptive efficacy of upadacitinib in pcJIA. Part 2:

[0455] To evaluate the long-term safety and tolerability of upadacitinib in pediatric subjects with pcJIA who have completed Part 1. To evaluate the descriptive efficacy of upadacitinib in pcJIA. Part 3:

[0456] To evaluate the long-term safety and tolerability of upadacitinib in pediatric individuals with pcJIA. To evaluate the descriptive efficacy of upadacitinib in pcJIA.

[0457] During Part 2 and Part 3, individuals who did not achieve at least a 20% improvement in the total number of active joints (joints with swelling) Petition 870250084429, dated 09 / 19 / 2025, pp. 124 / 189 115 / 143 not due to deformity or joints with LOM and with pain, tenderness, or both) compared to baseline at 2 consecutive visits in or after Week 8 discontinued the study medication and received treatment at the investigator's discretion, according to the local standard of care. Final points of the security test.

[0458] Safety assessments included the incidence of Treatment-Emergent Adverse Events (TEAEs), physical examination results, changes in vital sign measurements, and clinical laboratory tests (hematology and biochemistry) as measures of safety and tolerability for the entire duration of the study. Pharmacokinetic test endpoints

[0459] For Part 1, the values ​​for the pharmacokinetic parameters of upadacitinib including Cmax, time to observed maximum plasma concentration (Tmax), area under the plasma concentration versus time curve during a dosing interval (AUCtau) on Day 7, apparent oral clearance at steady state (CL / F) and half-life were determined using non-compartmental methods. Final points of the effectiveness test.

[0460] The following efficacy parameters were used to determine JIA response according to the American College of Rheumatology (ACR) and Juvenile Arthritis Disease Activity Score (JADAS): • Total number of active joints defined as: • Joints with swelling not due to deformity, OR • Joints with limited range of motion [LOM] with pain, tenderness, or both. • Number of joints with LOM • Child Health Assessment Questionnaire (C-HAQ) • Physician's Global Assessment of Disease Activity (visual analog scale [VAS]) Petition 870250084429, dated 09 / 19 / 2025, pp. 125 / 189 116 / 143 • Patient / Caregiver's Global Assessment of General Well-being (VAS) • Erythrocyte sedimentation rate (ESR) • C-reactive protein (CRP)

[0461] Based on these parameters, the following composite efficacy outcomes were evaluated: • Pediatric JIA ACR responses 30 / 50 / 70 / 90 / 100 • Change from baseline in JADAS responses 10 / 27 / 71, as well as JADAS-based criteria for low disease activity and remission (if deemed useful and appropriate). Example 2: Pharmacokinetics of Upadacitinib in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis (pcJIA); Analysis of Provisional Results from Example 1 Objective

[0462] The primary objective of this analysis was to characterize the pharmacokinetics of a Phase 1 study of upadacitinib in children with pcJIA (Example 1 PK analysis). Method

[0463] Patients (N = 51) diagnosed with pcJIA were enrolled in one of four groups in an open-label, multiple-dose study (Group 1, 12 to < 18 years, low dose; Group 2, 12 to < 18 years, high dose; Group 3, 6 to < 12 years, low dose; Group 4, 2 to < 6 years, low dose). The low and high doses were selected to provide comparable plasma exposures in pediatrics to adult doses of 15 mg and 30 mg once daily of the ER tablet formulation, respectively. Patients received weight-based doses of upadacitinib as either twice-daily (2x / day) immediate-release (IR) oral solution or once-daily extended-release (ER) tablet formulation. Pharmacokinetic assessment was performed at steady state on Day 7 of the study, after which all patients were able to continue the study with the low dose. Petition 870250084429, dated 09 / 19 / 2025, pp. 126 / 189 117 / 143 Results

[0464] A summary of the demographic data of the enrolled participants is provided in Table 3. Pharmacokinetic results were reported for 49 patients with evaluable drug concentrations on Day 7 of the Study.

[0465] In Group 1, the geometric means of the maximum plasma concentration (Cmax) and AUCo-24 of upadacitinib at steady state were 35.1 ng / mL and 269 ng^h / mL, respectively.

[0466] In Group 2, the geometric means of Cmax and AUCo-24 of upadacitinib were 69.8 ng / mL and 553 ng^h / mL, respectively.

[0467] In Group 3, the geometric means of Cmax and AUCo-24 of upadacitinib were 51.0 ng / mL and 346 ng^h / mL, respectively.

[0468] In Group 4, the geometric means of Cmax and AUCo-24 of upadacitinib were 46.6 ng / mL and 369 ng^h / mL, respectively.

[0469] The mean time to peak upadacitinib concentration was approximately 3 hours and 1 hour; and the mean harmonic functional half-life was approximately 5 hours and 2 hours for the once-daily ER tablet and twice-daily IR solution regimens, respectively. Apparent oral clearance of upadacitinib increased in patients with pcJIA with increasing body weight. Mean plasma concentration profiles of upadacitinib as a function of time for each group are presented by dosing regimen in Figure 2. Overall, the data indicate that plasma exposures of upadacitinib in pediatric patients with pcJIA were comparable to target adult patients with RA in the dosing regimens evaluated with the ER tablet or IR solution and at both low and high dose levels. These results support the use of a body weight-based dosing regimen in pediatric studies with upadacitinib. Table 3. Demographic summary of pediatric patients enrolled with pcJIA Group 1 (N = 9) Group 2 (N = 9) Group 3 (N = 19) Group 4 (N = 14) Average Age ± SD 14.9 ± 1.5 13.9 ± 1.2 9.5 ± 1.6 3.6 ± 1.5 Petition 870250084429, dated 09 / 19 / 2025, pp. 127 / 189 118 / 143 Group 1 (N = 9) Group 2 (N = 9) Group 3 (N = 19) Group 4 (N = 14a) (years) (Range) (13-17) (12-16) (6-12) (2-6) Weight (kg) Mean ± SD (Range) 61.3 ± 14.6 (42.0-92.9) 51.7 ± 13.0 (32.5-71.5) 37.8 ± 14.4 (19.7 ± 72.1) 15.1 ± 3.2 (11.0 ± 22.5) Sex Men, N (%) 2 (22.2) 1 (11.1) 4 (21.1) 3 (21.4) Women, N (%) 7 (77.8) 8 (88.9) 15 (78.9) 11 (78.6) Dosage Form Oral Solution, N (%) 0 (0.0) 0 (0.0) 7 (36.8) 14 (100.0) Tablet, N (%) 9 (100.0) 9 (100.0) 12 (63.2) 0 (0.0) a. Two individuals were excluded from the pharmacokinetic analysis. One individual mistakenly received half the dose, and the other individual had an incomplete PK sample collection. Example 3: Safety and Efficacy of Upadacitinib for Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis: An Interim Analysis of an Open-Label Phase 1 Trial (Analysis of Interim Results from Example 1 through Week 12) Objective

[0470] The objective of this study was to evaluate the safety and efficacy of upadacitinib in pediatric patients with pcJIA by age groups. Method

[0471] This open-label, 3-part, Phase 1 study (NCT03725007) involved pediatric patients aged 2 to <18 years with pcJIA and >5 active joints at 31 centers in North America, Europe, and Asia. In Part 1, two sequential groups of ascending multiple doses of UPA (low: 3 mg or 4 mg oral solution twice daily, or 15 mg tablet once daily; high: 6 mg or 8 mg oral solution or 30 mg tablet) were administered based on body weight groups (10 to <20, 20 to <30, and >30 kg) and age groups (2 to <6, 6 to <12, and 12 to <18 years of age) for 7 days. In Part 2 (long-term extension of Part 1) and Part 3 (additional safety cohort), low-dose UPA (3 mg or 4 mg oral solution, or 15 mg tablet) was administered based on body weight groups for up to 156 weeks. The data Petition 870250084429, dated 09 / 19 / 2025, pp. 128 / 189 119 / 143 efficacy scores included the American College of Rheumatology ACR 30, 50, and 70 response; the Childhood Health Assessment Questionnaire (C-HAQ); and the 27-point Juvenile Arthritis Disease Activity Score (JADAS-27) at week 12 among patients treated in Part 1 and Part 2. This was an interim analysis. Results

[0472] A total of 57 pediatric patients with a mean age (SD) of 9.5 (4.4) years, 78.9% female, and a mean weight (SD) of 38.1 (20.4) kg received UPA. In part 1, 8 (15.7%) of the 51 patients reported adverse events (AEs) over 7 days; no patients reported serious AEs or AEs leading to treatment discontinuation. In part 2 and part 3, 52 (91.2%) of the 57 patients reported AEs that were predominantly mild to moderate in severity (Table 4). AE rates were generally higher among patients aged 12 to <18 years. The most common adverse events (AEs) of special interest included elevated creatine phosphokinase (n = 6 / 57, 10.5%), liver dysfunction (n = 3 / 57, 5.3%), and neutropenia (n = 2 / 57, 3.5%). Six (31.6%) of the 19 patients in the 12 to <18 age range reported serious AEs, and 2 (10.5%) reported AEs leading to treatment discontinuation. No deaths occurred.A high proportion of patients across all age groups achieved ACR30, ACR50, and ACR70 responses at week 12 (Figures 3A, 3B, and 3C, respectively). With reference to Figures 3A to 3C, the numbers above the bars are the proportion of patients with a response (n / N). Improvement from baseline to week 12 in C-HAQ and JADAS-27 scores was observed across all age groups (Figures 3D and 3E, respectively). Overall, in pediatric patients with pcJIA, upadacitinib was safe and well-tolerated and associated with improvements in disease activity in a high proportion of patients at week 12 of this interim analysis. Table 4. Interim Safety Analysis of Upadacitinib up to 156 Weeks Petition 870250084429, dated 09 / 19 / 2025, pp. 129 / 189 120 / 143 AS, n (%) Age 2 to <6 years n = 14 Age 6 to <12 years n = 24 Age 12 to <18 years n = 19 Total N = 57 Any AE 11 (78.6) 22 (91.7) 19 (100) 52 (91.2) Any serious AE 0 0 6 (31.6) 6 (10.5) AE leading to discontinuation of the study drug 0 0 2 (10.5) 2 (3.5) Deaths 0 0 0 0 AEs of special interest Severe infection 0 0 1 (5.3) 1 (1.8) Opportunistic infection 0 0 1 (5.3) 1 (1.8) Hepatic disorder 0 2 (8.3) 1 (5.3) 3 (5.3) Anemia 1 (7.1) 0 0 1 (1.8) Neutropenia 0 2 (8.3) 0 2 (3.5) Lymphopenia 0 0 1 (5.3) 1 (1.8) Elevated creatine phosphokinase (CPK) 0 3 (12.5) 3 (15.8) 6 (10.5) Example 4: Pharmacokinetic Safety and Tolerability of Upadacitinib in Children with Atopic Dermatitis

[0473] The aim of this study was to characterize the pharmacokinetics (PK), safety and tolerability of upadacitinib in children with severe atopic dermatitis (AD). Method

[0474] This was an open-label, multiple-dose study. Patients with AD (N = 35) were enrolled in four cohorts (Cohort 1, 6 to < 12 years on low dose; Cohort 2, 6 to < 12 years on high dose; Cohort 3, 2 to < 6 years on low dose; Cohort 4, 2 to < 6 years on high dose). Upadacitinib was administered based on body weight with oral solution twice daily or extended-release tablet once daily. The low and high doses were selected to provide comparable plasma exposure in pediatric patients to the 15 mg and 30 mg QD doses in adults. Petition 870250084429, dated 09 / 19 / 2025, pp. 130 / 189 121 / 143 respectively. PK was assessed on Day 7 after the first dose. Safety was assessed throughout the study. Exploratory efficacy parameters were collected at specified time points. Results

[0475] The geometric means of Cmax and AUC over 0 to 24 hours at steady state were 33.1 and 35.2 ng / mL and 249 and 264 ng^h / mL in Cohorts 1 and 3; 95.5 and 101 ng / mL and 523 and 625 ng^h / mL in Cohorts 2 and 4, respectively.

[0476] Upadacitinib was generally safe and well tolerated. The most common AEs were COVID infection, headache, and abdominal discomfort. No new safety risks were identified compared to the known safety profile for upadacitinib.

[0477] In the 29 individuals with interim efficacy results available at week 12, 34.5% achieved a validated Investigator Global Assessment scale for AD score of 0 or 1 and 69.0% achieved an Eczema Area and Severity Index of at least 75% at Week 12 with upadacitinib treatment. Overall, the results support the use of a body weight-based dosing regimen for further investigation of upadacitinib in upcoming Phase 3 clinical trials in pediatric patients with AD. Example 5: Upadacitinib for the Treatment of Severe Atopic Dermatitis in Pediatric Individuals

[0478] This study was an open-label, phase 1, multiple-dose study to evaluate the pharmacokinetics (PK), safety, and tolerability of upadacitinib in pediatric subjects with severe atopic dermatitis (AD), which remains ongoing. Study design:

[0479] A schematic of the study design is provided in Figure 4. With reference to Figure 4, the study consisted of two parts. Petition 870250084429, dated 09 / 19 / 2025, pp. 131 / 189 122 / 143

[0480] Part 1 was an open-label, multiple-cohort, multiple-dose study consisting of two sequential ascending multiple-dose groups (low and high dose levels) in the two age groups. (Group 1: 6 to < 12 years and Group 2: 2 to < 6 years). The upadacitinib dose was administered based on the individual's body weight according to predefined body weight categories by dose level with at least 4 individuals in each body weight category (Table 5). The objectives of Part 1 were to evaluate the pharmacokinetics, activity, safety, and tolerability of multiple doses of upadacitinib in pediatric subjects with severe atopic dermatitis and to evaluate the palatability of the upadacitinib oral solution in pediatric subjects.

[0481] Part 2 was an open-label, long-term, multiple-dose extension to evaluate the safety and tolerability of upadacitinib. Subjects in Part 2 received open-label upadacitinib at the equivalent of the Low Dose level by body weight category. Table 5. Upadacitinib Dosage by Body Weight Category and Dose Level for Individuals Aged 2 to < 12 Years Body Weight Category* Current Dosing Regimen Starting with Protocol, Version 4.0 Dose Level 10 to <20 kg 20 to <30 kg >30 kg Low Dose 3 mg BID Oral Solution 4 mg BID Oral Solution 15 mg QD Tablet (Or 6 mg oral solution 2x / day if unable to swallow the tablet) High Dose 6 mg BID Oral Solution 8 mg BID Oral Solution 30 mg QD Tablet (Or 12 mg oral solution 2x / day if unable to swallow the tablet) Previous Dosing Regimen Before Protocol, Version 4.0 Dose Level 10 to <15 kg 15 to <25 kg 25 to <40 kg >40 kg Low Dose 1.6 mg IR 2x / day, oral solution 2 mg IR 2x / day, oral solution 7.5 mg ER Tablet 1x / day or ER tablet of 15 mg, 1x / day or Petition 870250084429, dated 09 / 19 / 2025, pp. 132 / 189 123 / 143 3 mg IR twice daily, oral solution; 6 mg IR twice daily, oral solution; High dose 3.2 mg IR twice daily, oral solution; 4 mg IR twice daily, oral solution; 15 mg ER tablet once daily or 6 mg IR twice daily, oral solution; 30 mg ER tablet once daily or 12 mg IR twice daily, oral solution 2X / day = twice a day; 1x / day = once a day *At least 4 children will be enrolled in each weight category.

[0482] Individuals who completed Part 1 had the option to enroll in Part 2 and receive low-dose upadacitinib on an open-label basis. During Part 2 of the study, concomitant topical AD medications are permitted during the study, at the investigator's discretion. Individuals with an Eczema Area and Severity Index (EASI) score worsened by 25% or more compared to their baseline EASI score at any 2 consecutive study visits after Week 4, or individuals who did not achieve at least a 50% improvement in their EASI score compared to baseline at 2 consecutive visits at or after Week 8, discontinued the study medication and received treatment at the investigator's discretion and in accordance with the local standard of care. Main eligibility criteria

[0483] Male or female individuals aged between 2 and less than 12 years at screening, and with a total body weight of 10 kg or more at baseline, were eligible for inclusion. The criteria for AD included: • Individual diagnosed with AD with symptom onset at least 6 months prior to the initial visit • The individual meets the Hanifin and Rajka criteria for AD. • Active disease, as defined by the following disease activity criteria at screening and baseline visits (all must be met): Eczema Area and Severity Index (EASI) score > 21; Petition 870250084429, dated 09 / 19 / 2025, pp. 133 / 189 124 / 143 The Validated Investigator Global Assessment Score for Atopic Dermatitis (vIGA-AD) equals 4; > 15% of body surface area affected by AD • Have a documented history (within 12 months prior to the Baseline Visit) of inadequate response or intolerance to topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) OR for whom the use of TCS and TCI is otherwise clinically inadvisable. Study population

[0484] Between January 31, 2019, and March 18, 2022, a total of 32 individuals enrolled in the study and received at least one dose of upadacitinib. Enrollment in Cohort 4 is ongoing. Another 20 individuals failed screening. The most common reason for pre-screening failure was the inability of individuals to meet the Hanifin and Rayka criteria for AD. One individual (3.1%) and 10 individuals (32.3%) in Part 1 and Part 2, respectively, discontinued upadacitinib. In Part 2, the most common reason for discontinuation was lack of efficacy (n = 4, 12.9%) and adverse event (n = 3, 9.7%).

[0485] The mean duration of exposure to upadacitinib in all study subjects in Part 1 was 7.0 days (range: 1 to 9 days) and 170 days (range: 1 to 770 days) in Part 2 (Table 6). Table 6. Exposure duration Median duration of exposure, in days (range) Part 1 Cohort 1 (N = 9) Cohort 2 (N = 8) Cohort 3 (N = 9) Cohort 4 (N = 6) Total (N = 32) 7.0 (7-7) 7.0 (7-7) 7.0 (1-9) 7.0 (7-7) 7.0 (1-9) Part 2 Age 6 to < 12 years (N = 17) Age 2 to < 6 years (N = 14) Total (N = 31) 425 (1-770) 23.0 (1-623) 170 (1-770)

[0486] Demographic data (Table 7) and baseline disease characteristics (Table 8) for all enrolled individuals are summarized. Most of the Petition 870250084429, dated 09 / 19 / 2025, pp. 134 / 189 Of the 143 individuals who received upadacitinib, 125 were female (n = 18, 56.3%), white (n = 19, 59.4%), and the mean age was 6.0 years (range: 2 to 11 years). Preliminary Clinical Pharmacokinetics

[0487] A summary of upadacitinib PK parameters on Day 7 is provided in Figures 5A, 5B, 5C, and 5D and Table 9. For Cohorts 1, 2, 3, and 4, there were 9, 8, 6, and 0 individuals who received upadacitinib in the dosing regimen defined by the original protocol, and 0, 0, 2, and 6 individuals who received upadacitinib in the revised dosing regimen. There was one additional individual who was enrolled in Cohort 3 but withdrew informed consent before the PK assessment. Therefore, this subject was not included in the PK analyses. For the analyses of plasma concentration versus time profiles and pharmacokinetic parameters, data from all these individuals were summarized based on cohort and dosing form (Figures 5A to 5D and Table 9). Preliminary Clinical Efficacy

[0488] Clinical efficacy parameters were collected as exploratory measures and to facilitate the benefit-risk assessment to justify the continuation of low-dose upadacitinib during Part 2, the long-term safety and tolerability portion of the study. No formal statistical comparisons were planned. Since all cohorts received low-dose upadacitinib in Part 2, the overall population was summarized for efficacy.

[0489] The pharmacodynamic activity of upadacitinib was demonstrated by efficacy outcome measures that assessed improvements from baseline at various time points in the study. A validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score of 0 or 1 (with at least two grades of reduction from baseline) at Week 12 was achieved by 9 / 27 individuals (33.3%) in the overall population across cohorts from the data cutoff (Table 10), signifying the achievement of clear or near-clear skin. Notably, activity was observed in the overall population despite 10 individuals in the Petition 870250084429, dated 09 / 19 / 2025, pp. 135 / 189 126 / 143 Cohorts 1, 2, and 3 required a dose increase to adequately achieve the target plasma exposure of upadacitinib.

[0490] A change from baseline in the Eczema Area and Severity Index by at least 75% (EASI 75) at Week 12 was achieved by 19 / 27 individuals (70.4%) for the overall population across cohorts from the data cutoff (Table 11). The mean and median percent change from baseline in EASI score at Week 12 for the overall population across cohorts was -79.8% and -82.9%, respectively, from the data cutoff (Table 12). For Tables 10 to 12, results are listed for the overall population, the 2 to < 6 year age cohort, the 6 to < 12 year age cohort, individuals included in the original dosing regimen, and individuals included after dosing regimen readjustment to achieve the target plasma exposure of upadacitinib.

[0491] Efficacy results are also summarized for the subgroup of 8 individuals from Cohorts 3 and 4 who were treated with a revised upadacitinib dosing regimen from study entry. Although efficacy results for only 7 of these individuals are available at Week 12, all individuals achieved an EASI 75 response at Week 12. EASI 75, vIGA-AD 0 / 1, and percent change from baseline EASI score results in these individuals were consistent with those of the overall population at the respective time points. For those 10 individuals enrolled under protocol version 3.0 or earlier, whose dose was increased at different time points due to the dose modification implemented with protocol v4.0, response rates measured by EASI75 and vIGA-AD score of 0 or 1 (with at least two degrees of reduction from baseline) improved numerically 12 weeks after dose increase. Table 7. Demographic data Cohort 1 (N = 9) Cohort 2 (N = 8) Cohort 3 (N = 9) Cohort 4 (N = 6) Total (N = 32) Sex, n (%) 3 (33.3) 2 (25.0) 4 (44.4) 5.1 14 Male 6 (66.7) 6 (75.0) 5 (55.6) (83.3) (43.8) Petition 870250084429, dated 09 / 19 / 2025, pp. 136 / 189 127 / 143 Female 1 (16.7) 18 (56.3) Age, years, median (range) 8.0 (6-11) 7.5 (6-10) 4.0 (2-5) 3.0 (2-4) 6.0 (2-11) Race, n (%) White Black or African American Asian American Indian / Alaska Native Native Hawaiian or other Pacific Islander Other Multiple 4 (44.4) 3 (33.3) 1 (11.1) 0 0 0 1 (11.1) 6 (75.0) 1 (12.5) 1 (12.5) 0 0 0 0 6 (66.7) 2 (22.2) 1 (11.1) 0 0 0 0 3 (50.0) 2 (33.3) 0 0 0 0 1 (16.7) 19 (59.4) 8 (25.0) 3 (9.4) 0 0 0 2 (6.3) Ethnicity, n (%) Hispanic or Latino Non-Hispanic or Latino 4 (44.4) 5 (55.6) 2 (25.0) 6 (75.0) 2 (22.2) 7 (77.8) 0 6 (100) 8 (25.0) 24 (75.0) Weight, kg, median (range) 26.8 (20.7 45.0) 33.7 (20.4 56.6) 18.8 (13.1 26.2) 15.2 (13.7 18.4) 22.0 (13.1 56.6) BMI, kg / m2, median (range) 15.9 (14.5 — 23.6) 21.1 (14.4 — 32.7) 16.0 (14.6 — 24.9) 16.2 (14.2 — 20.6) 16.2 (14.2 — 32.7) Table 8. Baseline disease characteristics Cohort 1 (N = 9) Cohort 2 (N = 8) Cohort 3 (N = 9) Cohort 4 (N = 6) Total (N = 32) Baseline beam-AD, n (%) < 4 4 0 9(100) 0 8(100) 0 9(100) 0 6(100) 0 32 (100) EASI, median (range) 27.4 (22.0-59.7) 31.6 (23.4-53.0) 28.8 (21.6-47.0) 28.5 (24.3-32.7) 28.8 (21.6-59.7) ASC (%) 50.0 (20-98) 40.5 (28-100) 44.0 (25 - 76) 56.0 (45 - 80) 50.0 (20 - 100) Disease history, n (%) 5 (55.6) 4 (44.4) 1 (12.5) 7 (87.5) 3 (33.3) 6 (66.7) 1 (16.7) 5 (83.3) 10 (31.3) 22 (68.8) Petition 870250084429, dated 09 / 19 / 2025, pp. 137 / 189 128 / 143 Yes No BSA = body surface area EASI = Eczema Area and Severity Index Table 9. Summary of Pharmacokinetic Parameters of Upadacitinib in Pediatric Individuals with AD Pharmacokinetic Parameter 6 to < 12 years (N=17) 2 to < 6 years (N = 13) Cohort 1 Cohort 3 Low Dose IR Solution (N = 5) ER Tablet (N = 4) IR Solution (N = 7) Cmax (ng / ml) 24.7 (27.9, 53) 47.7 (57.2, 72) 35.2 (47.4, 103) Tmax (h) 1.0 (0.5, 2.0) 2.5 (1.0, 4.0) 2.0 (1.0, 4.0) tl / 2b (h) 2.35 (0.59) 5.79 (1.20) 1.67 (0.66) AUCo-24c (ngh / mL) 224 (248, 55) 283 (289, 23) 264 (349, 107) CLss / F (L / h) 19.3(20.2, 31) 31.5 (34.2, 48) 15.6(18.6, 52) Cohort 2 Cohort 4 High Dose IR Solution (N = 3) ER Tablet (N = 5) IR Solution (N = 6) Cmax (ng / ml) 43.2 (46.8, 43) 154 (166, 50) 96.9(111, 51) Tmax (h) 2.0 (0.25, 4.0) 2.0 (0.5, 3.0) 0.75 (0.25, 1.0) tl / 2b (h) 1.68 (0.34) 4.93(1.06) 2.25 (0.514) AUCo-24c (ng h / mL) 347 (355, 25) 668 (679, 20) 579 (633, 38) CLss / F (L / h) 23.0 (23.6, 27) 39.1 (42.3, 37) 20.7 (23.6, 66) AUC0-24 = area under the plasma concentration-time curve during the last 24-hour dosing interval; 2x / day = twice daily; Cmax: maximum concentration; CLss / F = apparent total body clearance after oral administration (at steady state); ER = extended-release; IR = immediate-release; 1x / day = once daily; t1 / 2 = half-life; Tmax = time to maximum concentration a. Median (min - max). b. Harmonic mean (pseudo-standard deviation); half-life within a dosage range. c. The AUCo-24 for the formulated solution was calculated as AUC0-12 χ 2. Petition 870250084429, dated 09 / 19 / 2025, pp. 138 / 189 129 / 143 Note: Parameters are expressed as geometric mean (mean, % coefficient of variation), unless otherwise indicated. Table 10. Proportion of individuals who achieved a viGA-AD of 0 or 1 with at least two degrees of reduction from baseline at Week 12 (as observed) N Respondent, n (%) 95% CI Week 12 Total Age 2 to < 6 years Age 6 to < 12 years Enrollment up to protocol v3.0 Enrollment in or after protocol v4.0 27 12 15 20 7 9 (33.3) 3 (25.0) 6 (40.0) 6 (30.0) 3 (42.9) 16.5 - 54.0 5.5 - 57.2 16.3 - 67.7 11.9 - 54.3 9.9 - 81.6 Exact confidence intervals based on the Clopper-Pearson method. Table 11. Proportion of Individuals Who Achieved EASI 75 at Week 12 (As Observed) (Intention-to-Treat Population) N Respondent, n (%) 95% CI Week 12 Total Age 2 to < 6 years Age 6 to < 12 years Enrollment up to protocol v3.0 Enrollment in or after protocol v4.0 27 12 15 20 7 19 (70.4) 9 (75.0) 10 (66.7) 12 (60.0) 7 (100) 49.8 - 86.2 42.8 - 94.5 38.4 - 88.2 36.1 - 80.9 59.0 - 100.0 Exact confidence intervals based on the Clopper-Pearson method. Table 12. Change and Percentage Change in EASI in Week 12 (According to (Observed) (Population Intended to Treat) Change in EASI Percentage change in EASI N Mean Median Mean Median Week 12 -24.9 -23.8 (-29.0, - -79.8 -82.9 (-93.0, - Total 27 (9.61) 18.2) (19.0) 69.4) Age 2 to < 6 years d 9 -24.8 -25.2 (-26.8, - -82.0 -82.8 (-92.5, - Age 6 to < 12 years 1 2 1 (6.27) 20.4) (14.6) 73.3) Registration up to v3.0 of the protocol I 5 -25.0 -23.7 (-30.1, - -78.0 -85.7 (-94.6, - colo 20 7 (11.86) 16.3) (22.3) 60.0) Registration on or after the pro- -24.3 -23.8 (-28.1, - -76.6 -82.8 (-90.8, - protocol v4.0 (10.55) 17.1) (20.8) 64.6) Petition 870250084429, dated 09 / 19 / 2025, pp. 139 / 189 130 / 143 -26.5 (6.58) -25.2 (-31.9, 22.6) -88.8 (8.8) -88.8 (-98.5, 81.3) IQR = interquartile range; SD = standard deviation; Example 6: Immediate-release liquid formulation of upadacitinib

[0492] For pediatric use, an oral solution was developed to improve acceptability (palatability and swallowability), stability, and manufacturability. Specifically, a stable oral pharmaceutical solution of upadacitinib at 1 mg / mL and 0.5 mg / mL was prepared. Upadacitinib has good solubility at low pH (shown in Table 13). Thus, low pH buffers such as citrate, phosphate, tartrate, and formate are suitable for preparing the oral solution. Buffers with higher pH ranges, such as succinate and acetate, are also suitable (see Example 7), but will result in an oral suspension. Citrate buffer was selected because it has a favorable pKa (~3.1), which is close to the final pH of the oral solution. Consequently, a formulation was developed based on the solubility of upadacitinib in liquid with added citric acid and sodium citrate to completely dissolve upadacitinib.

[0493] Upadacitinib has a strong bitterness above concentrations of 0.1 mg / mL. An acceptable and palatable formulation has a bitterness intensity below 1.0. Therefore, a sweetener, flavor modifier or masking agent, and flavoring agent can mitigate the bitter taste of upadacitinib. Sweeteners or combinations of sweeteners, such as acesulfame potassium, sodium saccharin, sucralose, neotame, sucrose, maltitol, and xylitol are suitable for this oral solution. Flavor modifiers, such as sodium chloride, citric acid, and monoammonium glycyrrhizate, are also suitable for this oral solution. Flavoring agents such as cherry, orange, bubblegum, strawberry, and mango can increase the acceptability of the formulation. Petition 870250084429, dated 09 / 19 / 2025, pp. 140 / 189 131 / 143

[0494] Upadacitinib oral solution contains water and sweetener, which are potential causes of microbial growth. Upadacitinib oral solution is also a multidose formulation. Therefore, a preservative is added to the formulation to prevent microbial proliferation. Preservatives such as sodium benzoate and propylparaben are suitable based on the final pH of the oral solution. Other preservatives, such as sodium metabisulfite, benzoic acid, parahydroxybenzoate, potassium sorbate, and parahydroxybenzoic acid may also be used based on the final pH of the oral solution or suspension.

[0495] Upadacitinib 1 mg / mL oral solution C contained citric acid, sodium citrate, sucralose, sodium benzoate, and water. The 1 mg / mL oral solution C was clear and colorless to light yellow. The composition of certain 1 mg / mL and 0.5 mg / mL oral solutions is shown in Table 14. Table 13. Solubility of upadacitinib in different aqueous media at 37 °C. Medium pH (Nominal) pH (Final) Solubility (mg / ml) 0.1 N HCl 1.0 2.57 38.4 ± 1.5 50 mM Phosphate 2.01 3.08 10.5 ± 0.1 50 mM Citrate 3.00 3.39 4.48 ± 0.08 50 mM Citrate 4.01 4.16 1.00 ± 0.01 50 mM Citrate 5.03 5.01 0.289 ± 0.006 50 mM Citrate 6.01 5.96 0.196 ± 0.001 50 mM Phosphate 7.02 7.14 0.194 ± 0.001 50 mM Phosphate 8.02 7.99 0.200 ± 0.013 Carbonate 50 mM 9.02 9.11 0.199 ± 0.006 Water 6.02 6.92 0.240 ± 0.004 Petition 870250084429, dated 09 / 19 / 2025, pp. 141 / 189 132 / 143 Medium pH (Nominal) pH (Final) Solubility (mg / ml) Simulated Fed-State Intestinal Fluid (FeSSIF) 5.01 5.10 0.455 ± 0.006 FeSSIF 6.50 6.58 0.262 ± 0.003 Table 14. Proposed compositions of upadacitinib oral solutions. ABC Formulation 1 mg / mL 0.5 mg / mL 1 mg / mL Component Function Quantity (g) Upadacitinib free base Active ingredient 0.100 0.050 0.100 Sodium benzoate Preservative 0.050 0.030 0.030 Anhydrous citric acid pH modifier 0.288 0.213 0.213 Sodium citrate dihydrate Buffer — 0.116 0.045 Sucralose Sweetener 0.900 0.900 0.900 Purified water Solvent qs to 100 qs to 100 qs to 100 Example 7. Liquid formulation of upadacitinib, immediate-release or extended-release (suspension).

[0496] An immediate-release oral suspension is prepared to accommodate a higher dosage or a higher pH. The buffers, preservatives, and sweeteners listed in Example 6 may be applied to this formulation. Generally, a sustained-release liquid formulation is prepared to provide prolonged release of upadacitinib for once-daily administration using a release rate modifier, such as an ion-exchange resin. Liquid dosage forms comprise an upadacitinib-ion-exchange resin complex. The upadacitinib-ion-exchange resin complex comprises upadacitinib or a pharmaceutically acceptable salt thereof linked to an ion-exchange resin. Suitable ion-exchange resins include, but are not limited to, a sulfonated copolymer comprising styrene and divinylbenzene. In some of these embodiments, the mobile or exchangeable cation is sodium. An exemplary cationic ion-exchange resin is AmberLite™ IRP 69 (DuPont). Petition 870250084429, dated 09 / 19 / 2025, pp. 142 / 189 133 / 143 Example 8: Safety and Efficacy of Upadacitinib for Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis: An Interim Analysis of an Open-Label Phase 1 Trial (Analysis of Interim Results from Example 1 to Week 48)

[0497] This Example provides additional data up to week 48 for the study described in Example 1. Objective

[0498] The aim of this study was to evaluate the pharmacokinetics, efficacy and safety of upadacitinib in pediatric patients with polyarticular juvenile idiopathic arthritis (pcJIA). Method

[0499] As described above in Example 1, this was an open-label Phase 1 study involving patients aged 2 to <18 years with pcJIA. Patients received upadacitinib doses based on body weight using a twice-daily (2x / day) oral solution or once-daily (1x / day) extended-release tablet (see Table 15). The study included a 7-day pharmacokinetic assessment, followed by a long-term efficacy and safety assessment for up to 156 weeks, including an additional long-term safety cohort. This interim analysis includes all available pharmacokinetic and safety data and efficacy data collected up to Week 48, excluding those from patients enrolled in the long-term safety cohort. A schematic representation of the study design, including body weight categories, is provided as Figure 6. Table 15. Upadacitinib Dosage by Body Weight Category and Dose Level for Individuals Aged 2 to < 12 Years_________________________________________ Body Weight Category* Current Dosing Regimen Starting with Protocol, Version 4.0 Dose Level 10 to < 20 kg 20 to < 30 kg > 30 kg Low Dose 3 mg BID Oral Solution 4 mg BID Oral Solution 15 mg QD Tablet (Or 6 mg of oral solution 2x / day if unable to swallow the tablet) Petition 870250084429, dated 09 / 19 / 2025, pp. 143 / 189 134 / 143 Body Weight Category* Current Dosing Regimen Starting with Protocol, Version 4.0 High Dose 6 mg BID Oral Solution 8 mg BID Oral Solution 30 mg QD Tablet (Or 12 mg oral solution 2x / day if unable to swallow the tablet) Previous Dosing Regimen Before Protocol, Version 4.0 Dose Level 10 to < 15 kg 15 to < 25 kg 25 to < 40 kg > 40 kg Low Dose 1.6 mg IR 2x / day, oral solution 2 mg IR 2x / day, oral solution 7.5 mg ER Tablet, 1x / day or 3 mg IR 2x / day, oral solution 15 mg ER Tablet, 1x / day or 6 mg IR 2x / day, oral solution High Dose 3.2 mg IR 2x / day, oral solution 4 mg IR 2x / day, oral solution Tablet ER 15 mg, once daily or 6 mg IR twice daily, oral solution. ER 30 mg, once daily or 12 mg IR twice daily, oral solution. 2X / day = twice a day; 1x / day = once a day *At least 4 children will be enrolled in each weight category. Results Patients and Disposition

[0500] A summary of patient disposition is provided in Figure 7. A summary of patient demographic and disease characteristics is provided in Table 16. With reference to Table 16, the majority of enrolled patients were female (45 / 57, 78.9%) and had RF-negative polyarticular JIA (42 / 57, 73.7%). Enrolled patients ranged in age from 2 to 17 years, with a mean disease duration of 3 years. At baseline, 23 (40.4%) patients were receiving methotrexate, 11 (19.3%) patients were receiving oral corticosteroids, and 14 (24.6%) patients reported prior use of bDMARDs. Table 16. Baseline demographic and disease characteristics Mean ± SD (range) or n (%) All patients (n = 57) Female, n (%) 45 (78.9%) Age, years, mean ± SD (range) 9.5 ± 4.41 (2 - 17) White, n (%) 55 (96.5%) Weight, kg, mean ± SD (range) 38.05 ± 20.380 (11.0 - Petition 870250084429, dated 09 / 19 / 2025, pp. 144 / 189 135 / 143 Mean + / - SD (range) or n (%) All patients (n = 57) 92.9) Type pcJIA Extended oligoarticular JIA, n (%) 7 (12.3) RF-negative polyarticular JIA, n (%) 42 (73.7) RF-positive polyarticular JIA, n (%) 7 (12.3) Systemic JIA with active arthritis and without systemic active characteristics, n (%) Duration of pcJIA diagnosis, years, mean ± SD (range) 2.959 ± 3.3387 (0.05 - 13.23) Active joints, mean ± SD (range) 11.1 ± 7.74 (5 - 48) C-HAQ 1.047 ± 0.7746 (0.00 - 2.88) CRP (mg / L) 9.11 ± 18.958 (0.2 - 92.3) ESR (n = 53) 19.5 ± 19.02 (2 - 94) Oral corticosteroids, n (%) 11 (19.3) Methotrexate, n (%) 23 (40.4) Prior exposure to bDMARDs 14 (24.6) bDMARDs, biological drugs that modify the course of rheumatic disease; CRP, C-reactive protein (normal range < 2.87 mg / L); JIA, juvenile idiopathic arthritis; EST, erythrocyte sedimentation rate (normal range 3 to 15 mm / h); pcJIA, polyarticular juvenile idiopathic arthritis; n, number of patients; RF, rheumatoid factor; SD, standard deviation Pharmacokinetics

[0501] Mean plasma concentration profiles over time by dose level and formulations compared with simulated adult reference profiles based on pharmacokinetic analyses of upadacitinib data from phase 3 RA studies are presented in Figures 8A to 8C. The adult RA reference represents the median (dashed line) and (5th, 95th) percentiles (shaded area) of model-predicted plasma concentrations of upadacitinib in adult RA patients after once-daily tablet administration. These reference pharmacokinetic profiles were simulated using a previously developed model for RA patients. Symbols with decreased opacity (more than 12 to 24 hours) for twice-daily IR regimens are replicated from observed data (more than 0 to 12 Petition 870250084429, dated 09 / 19 / 2025, pages 145 / 189 136 / 143 hours) to explain the difference in dosing frequency between the twice-daily oral solution and the once-daily tablet formulations.

[0502] A summary of the steady-state pharmacokinetic parameters of upadacitinib (i.e., on Day 7) after administration of upadacitinib in patients enrolled in Part 1 is provided in Table 17. During the pharmacokinetic evaluation, 13 patients in Group 3 and 12 patients in Group 4 received revised doses, and all other patients received the original doses. The Cmax of upadacitinib was reached within approximately 3 hours and 1 hour after administration of the ER tablet and the oral IR solution formulations, respectively. The functional t1 / 2 of upadacitinib was approximately 5 hours within a once-daily dosing interval for the ER tablet and 2 hours within a twice-daily dosing interval for the IR solution. Table 17. Geometric Mean (Mean, % CV) Pharmacokinetic Parameters of Upadacitinib Study Group and Dosing Regimen (Part 1)_________________ Age 12 to < 18 years Age 6 to < 12 years Age 2 to < 6 years Group 1: low dose Group 2: high dose Group 3: low dose Group 4: low dose Pharmacokinetic Parameters (units) Tablet 1x / day (N = 9) Tablet 1x / day (N = 9) Tablet 1x / day (N = 12) Solution 2x / day (n = 7) Combined (n = 19) Solution 2x / day (n = 12)i Cmax (ng / ml) 35.1 (37.2, 35) 69.8 (71.2, 19) 46.9 (52.3, 46) 58.9 (62.5, 35) 51.0 (56.1, 41) 46.6 (55.8, 56) Tmaxa (h) 3.0 (1.0-6.0) 4.0 (2.0-6.0) 3.0 (1.0-6.0)f 1.0 (0.51.0) — 1.0 (0.5 - 2.0) ti / 2b functional (h) 5.53 (1.77)e 4.79 (1.12) 5.20 (0.949)f 2.39 (0.277) — 2.33 (0.351)j AUCtau (ng»h / mL) 269 (282, 32)e 553 (572, 26) 318 351 (41 )f 198 (209, 36) — 184 (217, 61) AUC0-24c (ng^h / mL) 269 ​​(282, 32) and 553 (572, 26) 318 351 (41)f 397 (417, 36) 346 (377, 38)h 369 (433, 61) Petition 870250084429, dated 09 / 19 / 2025, pp. 146 / 189 137 / 143 Age 12 to < 18 years Age 6 to < 12 years Age 2 to < 6 years CLss / F (L / h) 55.7 (58.2, 32)e 46.5 (49, 38) 41.6 46.7 (67)f 19.7 (20.2, 25) — 15.0 (16.8, 49) CLss / F_adjustedd (L / h) 38.1 (39.8, 32)e 31.8 (33.5, 38) 28.5 32.0 (67)f 19.7 (20.2, 25) 24.7 (27.4, 65)h 15.0 (16.8, 49) AUC, area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) or over a dose interval (AUCtau); BID, twice daily. Cmax, maximum plasma concentration; CLss / F, apparent oral clearance at steady state; CLss / F_adjusted, CLss / F adjusted for bioavailability; n, number of patients; QD, once daily; Tmax, time to maximum plasma concentration; functional t1 / 2, functional half-life. the. Median (minimum to maximum). b. Harmonic mean (pseudo-standard deviation). c. For QD tablets, AUC0-24 = AUCtau; for twice-daily oral solution, AUC024 = AUCtau x 2. d. CLss / F adjusted for the difference in bioavailability between the formulations. For once-daily tablets, adjusted CLss / F = 0.684 x ​​CLss / F; For twice-daily oral solution, adjusted CLss / F = CLss / F. e. n = 8. f. n = 11. g. Cmax, AUCo-24 and adjusted CLss / F of the ER tablet and IR oral solution formulations are combined and summarized together for Group 3. h. n = 18. One patient was excluded for receiving an incorrect dose throughout Part 1, and another patient who missed a dose on Day 7 due to an AS of vomiting was also excluded. j. n = 10. Effectiveness Petition 870250084429, dated 09 / 19 / 2025, pp. 147 / 189 138 / 143

[0503] By the data cutoff date, 50 of the 51 patients in Parts 1 and 2 had efficacy results available at Week 12, and 37 patients had efficacy results available by Week 48, at which time 35 of the 37 patients were being treated with the revised upadacitinib dosing regimen. A summary of JIA ACR 30 / 50 / 70, C-HAQ, and JADAS-27 CRP responses at Week 12 is presented in Figures 9A to 9E, respectively. Overall, the percentage of patients in Parts 1 and 2 who achieved a JIA ACR 30 / 50 / 70 / 90 / 100 response at Week 12 was 91.8 / 89.8 / 69.4 / 49.0 / 32.7%. The two youngest age groups (2 to < 6 years and 6 to < 12 years) had similar improvements in JIA ACR responses, and the oldest age group (12 to < 18 years) had numerically lower rates of JIA ACR responses compared to the younger age groups, without statistical significance. The response to upadacitinib was rapid, with 61.2% of patients achieving JIA ACR 30 as early as Week 1.JIA ACR responses continued to improve at Week 24 and were generally maintained through Week 48 (Figure 10A). Key additional efficacy measures, including C-HAQ, total number of active joints, Physician's Global Assessment of Disease Activity (VAS), Patient / Parent's Global Assessment of General Wellbeing (VAS), and JADAS-27 CRP, JADAS-27 ESR, ESR, and CRP are summarized in Table 18. Across these efficacy measures at Week 12, improvement from baseline was observed in all age groups, and changes from baseline were consistent across age groups. Changes in JADAS-27 ESR were similar to those in JADAS-27 CRP. Twenty-nine (29) of 50 patients (58%) achieved JADAS27 CRP < 3.8 and 16 of 50 patients (32%) achieved JADAS-27 CRP < 1 at Week 12. The proportions of patients who achieved these responses increased further at Week 24 and were generally maintained through Week 48 (Figures 10B, 10C and 10D). Table 18. Summary of Selected Effectiveness Outcomes in Week 12 Petition 870250084429, dated 09 / 19 / 2025, pp. 148 / 189 139 / 143 (Parts 1 and 2) Efficacy outcomes by age group n Mean baseline Mean visits Change from baseline within range Mean (95% CI) Median (min, max) C-HAQ 2 to < 6 years 13 0.85 0.54 -0.31 (-0.77, 0.15) -0.38 (4.3, 1.1) 6 to < 12 years 19 1.07 0.43 -0.64 (-0.95, -0.34) -0.38 (4.9, 1.1) 12 to < 18 years 18 1.04 0.71 -0.33 (-0.58, -0.09) -0.31 (-1.1, 0.5) Total 50 1.00 0.56 -0.45 (-0.63, -0.27) -0.38 (-1.9, 1.1) Total number of active joints 2 to < 6 years 13 8.1 1.1 -7.0 (-8.8, -5.2) -6.0 (-12, -3) 6 to < 12 years 19 11.6 1.4 -10.2 (-13.0, -7.5) -8.0 (-24, -4) 12 to < 18 years 18 11.7 1.5 -10.2 (-13.3, -7.2) -9.0 (-25, 0) Total 50 10.7 1.3 -9.4 (-10.9, -7.8) -8.0 (-25, 0) Physician's overall assessment of disease activity (VAS) 2 to < 6 years 13 51.6 6.1 -45.5 (-53.6, -37.5) -49.0 (-72, -25) 6 to < 12 years 19 59.3 4.1 -55.3 (-65.2, -45.3) -55.0 (-100, -28) 12 to < 18 years 15 62.4 16.1 -46.3 (-63.2, -29.4) -41.0 (-94, 9) Total 47 58.2 8.4 -49.7 (-56.4, -43.0) -49.0 (-100,9) Patient / Parent Global Assessment of General Well-being (VAS) 2 to < 6 years 13 48.4 15.6 -32.8(-52.2, -13.4) -38.0(-81.37) 6 to < 12 years 19 42.3 13.5 -28.8(-39.2, -18.4) -29.0(-61.9) 12 to < 18 years 18 45.8 26.2 -19.6(-28.3, -10.8) -23.0 (-45.8) Total 50 45.1 18.6 -26.5(-33.2, -19.8) -26.0(-81.37) JADAS27-CRP 2 to < 6 years 13 16.81 3.17 -13.65 (-16.88, 10.42) -12.86 (-22.4, -5.1) 6 to < 12 years 19 19.40 2.85 -16.55 (-19.42, 13.68) -16.90 (-28.9, -7.2) 12 to < 18 years 15 20.30 5.58 -14.72 (-18.88, 10.55) -14.40 (-31.1, -0.3) Total 47 18.97 3.81 -15.16 (47.02, 13.30) -14.59 (-31.1, -0.3) JADAS27-ESR 2 to < 6 years 11 16.23 3.14 -13.09 (-16.73, -9.46) -13.70 (-22.4, -5.8) 6 to < 12 years 19 19.91 2.83 -17.08 (-20.19, 13.98) -16.90 (-30.6, -7.2) 12 to < 18 years 15 20.41 5.78 -14.63 (-18.86, 10.41) -13.70 (-31.7, -0.2) Total 45 19.18 3.89 -15.29 (-17.30, 13.28) -14.40 (-31.7, -0.2) ESR, Petition 870250084429, dated 09 / 19 / 2025, pp. 149 / 189 140 / 143 2 to < 6 years 9 25.6 11.2 -14.3(-25.9,-2.8) -7.0 (-39.2) 6 to < 12 years 19 18.8 8.9 -9.9(-17.3,-2.5) -4.0(-41.7) 12 to < 18 years 16 13.6 13.3 -0.3 (-5.8, 5.3) -2.5(-17.26) Total 44 18.3 11.0 -7.3(-11.7,-2.9) -4.0(-41.26) CRP 2 to < 6 years 11 19.362 0.933 -18.429 (-36.310, 0.548) -4.450 (-77.05, 0.06) 6 to < 12 years 18 4.573 1.312 -3.261 (-6.110, 0.412) -0.820 (-16.70, 5.50) 12 to < 18 years 18 2.777 2.981 0.204 (-2.836, 3.245) -0.150 (-16.49, 17.20) Total 47 7.346 1.862 -5.484 (-9.981, 0.987) -0.390 (-77.05, 17.20) Efficacy outcomes by age group n Respondent n (%), [95% CI] JADAS27-CRP < 3.8 (minimal disease activity) 2 to < 6 years 13 9 (69.2), [38.6, 90.9] 6 to < 12 years 19 13(68.4), [43.4, 87.4] 12 to < 18 years 18 7(38.9), [17.3, 64.3] Total 50 29 (58.0), [43.2, 71.8] JADAS27-CRP < 1 (inactive disease) 2 to < 6 years 13 5(38.5), [13.9, 68.4] 6 to < 12 years 19 9(47.4), [24.4, 71.1] 12 to < 18 years 18 2(11.1), [1.4, 34.7] Total 50 16 (32.0), [19.5, 46.7] Discussion

[0504] In this open-label Phase 1 study, upadacitinib administered as a fixed dose per body weight category was effective and well tolerated in pediatric patients with pcJIA. The pharmacokinetics of upadacitinib observed in pediatric patients with pcJIA for the once-daily regimen using the ER formulation and the twice-daily regimen using the IR formulation were consistent with the pharmacokinetics of upadacitinib characterized in adults for the respective formulations.

[0505] The original upadacitinib dosing regimen was selected by leveraging pharmacokinetic data of upadacitinib in adult patients with RA and allometric clearance and volume of distribution scaling based on body weight, with the aim of achieving upadacitinib exposures in patients with pcJIA. Petition 870250084429, dated 09 / 19 / 2025, pp. 150 / 189 141 / 143 similar to the exposures that have been shown to be ideal in adult patients with RA. In this study, a preliminary population pharmacokinetic analysis indicated that the apparent oral clearance of upadacitinib in pediatric patients was underestimated when an estimate of upadacitinib clearance in adult RA patients with a typical exponent of 0.75 was used to describe the relationship between body weight and clearance. Consequently, a revised dosing regimen was developed and used in younger pediatric patients (mostly 6 to <12 years and 2 to <6 years) to enable the achievement of upadacitinib exposures comparable to the target exposures in adults with RA.Based on previous analyses, the median area (5th, 95th percentile) of upadacitinib under the plasma concentration-time curve (AUC) at steady state in adult patients with RA in phase 3 studies was 358 (234, 701) and 708 (466, 1332) ng^h / mL after daily administration of 15 mg and 30 mg ER tablets, respectively. Compared to the median target exposure in adults (AUC0-24), the relative median AUC0-24 of upadacitinib within each group in this study ranged from approximately 0.77 to 1.07 (Table 19). In younger pediatric patients, where most received revised doses, the observed exposures to upadacitinib were nearly identical to the target exposures in adult patients with a ratio of 1.01.

[0506] In this study, a twice-daily IR oral solution formulation was used for patients with lower body weight (i.e., < 30 kg) or unable to swallow tablets. Despite the distinct pharmacokinetic profiles due to the different dosing frequency, the twice-daily oral solution is expected to provide similar efficacy in pcJIA compared to the once-daily tablet if a similar upadacitinib AUC0-24 can be achieved. This is supported by previously conducted exposure-response analyses of key efficacy outcomes in adult patients with RA, where a model developed based on data from a twice-daily capsule formulation in studies Petition 870250084429, dated 09 / 19 / 2025, pp. 151 / 189 Phase 2 studies 142 / 143 successfully predicted the observed efficacy of the once-daily tablet formulation in Phase 3 studies. Analyses showed that upadacitinib IR twice-daily and ER once-daily regimens providing similar AUC0-24 were predicted to achieve similar efficacy responses.

[0507] Based on descriptive analyses of efficacy outcomes, improvements were observed in measures of pcJIA disease activity, pain, function, and general well-being after upadacitinib administration at Week 12 in this study, and were generally maintained through Week 48. Improvements with upadacitinib were observed across all age groups evaluated, which included pcJIA patients aged 2 to <18 years, with numerically higher response rates in patients aged 2 to <12 years than those aged 12 to <18 years. Notably, most patients in the older age group had longer disease duration and prior exposure to bDMARDs. In comparison, most patients in the younger age groups had shorter disease duration and no prior bDMARD exposure (Table 16). There were no patients with a history of uveitis, and no uveitis events occurred during the study.The safety profile of upadacitinib in pediatric patients with pcJIA was generally consistent with the currently known safety profile of upadacitinib in adults and adolescents with inflammatory conditions.

[0508] Overall, upadacitinib was well tolerated and effective in patients with pcJIA across all age groups (ages 2 to <18 years) with plasma exposures comparable to adult patients with RA in the dosing regimens evaluated. No new safety risks were observed in patients with pcJIA, and the benefit-risk profile of upadacitinib was assessed as favorable based on the safety and efficacy results of the study to date. Table 19. Comparison of Plasma Exposures of Upadacitinib between Pediatric Patients with pcJIA and Adult Patients with RA_________________________ AUC0-24 median Ratio for adults Petition 870250084429, dated 09 / 19 / 2025, pages 152 / 189 143 / 143 (ng^h / mL) Low dose level (corresponding to the 15 mg ER tablet in adults) Adult patients with RA Group 1 (12 to <18 years) Group 3 (6 to <12 years) Group 4 (2 to <6 years) 358 278 0.78 383 1.07 360 1.01 High dose level (corresponding to the 30 mg ER tablet in adults) Adult patients with RA Group 2 (12 to <18 years) 708 547 0.77 ER, extended-release; pcJIA, polyarticular juvenile idiopathic arthritis; RA, rheumatoid arthritis Petition 870250084429, dated 09 / 19 / 2025, pp. 153 / 189

Claims

1 / 19 CLAIMS 1. A method for treating polyarticular juvenile idiopathic arthritis (pcJIA) in a pediatric patient, wherein the method is CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administering upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); If the pediatric patient has a body weight in the range of approximately 20 kg to less than approximately 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily);and if the pediatric patient has a body weight of approximately 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg once daily). Petition 870250084429, dated 09 / 19 / 2025, p. 154 / 189 2 / 19; 2. Method according to claim 1, CHARACTERIZED by twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib to the pediatric patient as a stable oral pharmaceutical solution.

3. Method according to claim 2, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

4. Method according to claim 2 or 3, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL.

5. Method, according to any one of claims 1 to 4, CHARACTERIZED by once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib being performed on the pediatric patient as a prolonged-release tablet.

6. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response 30 in 12 weeks after the first daily administration.

7. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR 50 response within 12 weeks after the first daily administration.

8. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response of 70 within 12 weeks after the first daily administration.

9. Method, according to any of claims 1 to 4, Petition 870250084429, dated 09 / 19 / 2025, p. 155 / 189 3 / 19 CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response of 90 within 12 weeks after the first daily administration.

10. Method for the treatment of systemic juvenile idiopathic arthritis (SJIA) in a pediatric patient, the method being CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administer upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily);and if the pediatric patient has a body weight of approximately 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg once daily). Petition 870250084429, dated 09 / 19 / 2025, p. 156 / 189 4 / 19; 11. Method according to claim 10, CHARACTERIZED by twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib to the pediatric patient as a stable oral pharmaceutical solution.

12. Method according to claim 11, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

13. Method according to claim 11 or 12, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL.

14. Method according to claim 10, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

15. Method for treating atopic dermatitis (AD) in a pediatric patient under twelve years of age, the method being CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administering upadacitinib twice daily at a dose of 3 mg each (3 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 6 mg each (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 Petition 870250084429, dated 09 / 19 / 2025, p.157 / 189 5 / 19 kg less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient has a body weight of about 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg once daily).

16. Method according to claim 15, CHARACTERIZED by twice-daily administration of a 3 mg dose of upadacitinib, twice-daily administration of a 4 mg dose of upadacitinib, twice-daily administration of a 6 mg dose of upadacitinib, twice-daily administration of an 8 mg dose of upadacitinib, or twice-daily administration of a 12 mg dose of upadacitinib to the pediatric patient as a stable oral pharmaceutical solution.

17. Method according to claim 16, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

18. Method according to claim 16 or 17, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL. Petition 870250084429, dated 19 / 09 / 2025, pp. 158 / 189 6 / 19 19. Method according to claim 15, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

20. Method, according to any one of claims 15 to 19, CHARACTERIZED by the pediatric patient achieving an EASI 75 response within 12 weeks after the first daily administration.

21. Method, according to any one of claims 15 to 19, CHARACTERIZED by the pediatric patient achieving an EASI 90 response within 12 weeks after the first daily administration.

22. Method, according to any one of claims 15 to 19, CHARACTERIZED by the pediatric patient achieving an EASI 100 response within 12 weeks after the first daily administration.

23. Method, according to any one of claims 15 to 19, CHARACTERIZED by the pediatric patient achieving a score on the Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scale of 0 or 1 12 weeks after the first daily administration.

24. Method for treating psoriatic arthritis (PsA) in a pediatric patient, the method being CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administering upadacitinib twice daily at a dose of 3 mg each (3 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 6 mg each (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 Petition 870250084429, dated 09 / 19 / 2025, p.159 / 189 7 / 19 kg less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient has a body weight of about 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg once daily).

25. Method according to claim 24, CHARACTERIZED in that twice-daily administration of a 3 mg dose of upadacitinib, twice-daily administration of a 4 mg dose of upadacitinib, twice-daily administration of a 6 mg dose of upadacitinib, twice-daily administration of an 8 mg dose of upadacitinib, or twice-daily administration of a 12 mg dose of upadacitinib occurs to the pediatric patient as a stable oral pharmaceutical solution.

26. Method according to claim 25, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

27. Method according to claim 25 or 26, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL. Petition 870250084429, dated 19 / 09 / 2025, pp. 160 / 189 8 / 19 28. Method according to claim 24, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

29. Method for treating ankylosing spondylitis (AS) in a pediatric patient, the method being CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administer upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily);and if the pediatric patient has a body weight of approximately 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg Petition 870250084429, dated 09 / 19 / 2025, page 161 / 189 9 / 19 once daily).

30. Method according to claim 29, CHARACTERIZED by twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib to the pediatric patient as a stable oral pharmaceutical solution.

31. Method according to claim 30, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

32. Method according to claim 30 or 31, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL.

33. Method according to claim 29, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

34. Method for treating non-radiographic axial spondyloarthritis (nr-axSpA) in a pediatric patient, the method being CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administering upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); Petition 870250084429, dated 09 / 19 / 2025, p.162 / 189 10 / 19 if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient has a body weight of approximately 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg once daily).

35. Method according to claim 34, CHARACTERIZED by twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib to the pediatric patient as a stable oral pharmaceutical solution.

36. Method according to claim 35, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

37. Method according to claim 35 or 36, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL. Petition 870250084429, dated 19 / 09 / 2025, pp. 163 / 189 11 / 19 38. Method according to claim 34, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

39. Method for treating hidradenitis suppurativa in a pediatric patient, the method being characterized by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administer upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily);and if the pediatric patient has a body weight of approximately 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg Petition 870250084429, dated 09 / 19 / 2025, page 164 / 189 12 / 19 once daily).

40. Method according to claim 39, CHARACTERIZED in that twice-daily administration of a 3 mg dose of upadacitinib, twice-daily administration of a 4 mg dose of upadacitinib, twice-daily administration of a 6 mg dose of upadacitinib, twice-daily administration of an 8 mg dose of upadacitinib, or twice-daily administration of a 12 mg dose of upadacitinib occurs to the pediatric patient as a stable oral pharmaceutical solution.

41. Method according to claim 40, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

42. Method according to claim 40 or 41, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL.

43. Method according to claim 39, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

44. Method for treating systemic lupus erythematosus in a pediatric patient, the method being CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administering upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 Petition 870250084429, dated 09 / 19 / 2025, p.165 / 189 13 / 19 kg less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient has a body weight of about 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg once daily).

45. Method according to claim 44, CHARACTERIZED by twice-daily administration of a 3 mg dose of upadacitinib, twice-daily administration of a 4 mg dose of upadacitinib, twice-daily administration of a 6 mg dose of upadacitinib, twice-daily administration of an 8 mg dose of upadacitinib, or twice-daily administration of an 8 mg dose of upadacitinib to the pediatric patient as a stable oral pharmaceutical solution.

46. ​​Method according to claim 45, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

47. Method according to claim 45 or 46, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL. Petition 870250084429, dated 19 / 09 / 2025, pp. 166 / 189 14 / 19 48. Method according to claim 44, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

49. Method for treating ulcerative colitis in a pediatric patient, the method being characterized by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administering upadacitinib twice daily at a dose of 3 mg each time (3 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 kg to less than about 30 kg: (i) administering upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily);and if the pediatric patient has a body weight of approximately 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg Petition 870250084429, dated 09 / 19 / 2025, page 167 / 189 15 / 19 once daily).

50. Method according to claim 49, CHARACTERIZED by twice-daily administration at a dose of 3 mg of upadacitinib, twice-daily administration at a dose of 4 mg of upadacitinib, twice-daily administration at a dose of 6 mg of upadacitinib, twice-daily administration at a dose of 8 mg of upadacitinib, or twice-daily administration at a dose of 12 mg of upadacitinib to the pediatric patient as a stable oral pharmaceutical solution.

51. Method according to claim 50, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

52. Method according to claim 50 or 51, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL.

53. Method according to claim 49, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

54. Method for the treatment of Crohn's disease in a pediatric patient, the method being CHARACTERIZED by comprising administering a therapeutically effective amount of upadacitinib to the pediatric patient, wherein if the pediatric patient has a body weight in the range of about 10 kg to less than about 20 kg: (i) administering upadacitinib twice daily at a dose of 3 mg each (3 mg twice daily), or (ii) administering upadacitinib twice daily at a dose of 6 mg each (6 mg twice daily); if the pediatric patient has a body weight in the range of about 20 Petition 870250084429, dated 09 / 19 / 2025, p.168 / 189 16 / 19 kg less than about 30 kg: (i) administer upadacitinib twice daily at a dose of 4 mg each time (4 mg twice daily), or (ii) administer upadacitinib twice daily at a dose of 8 mg each time (8 mg twice daily); and if the pediatric patient has a body weight of about 30 kg or more: (i) administer upadacitinib twice daily at a dose of 6 mg each time (6 mg twice daily), (ii) administer upadacitinib twice daily at a dose of 12 mg each time (12 mg twice daily), (iii) administer upadacitinib once daily at a dose of 15 mg (15 mg once daily), or (iv) administer upadacitinib once daily at a dose of 30 mg (30 mg once daily).

55. Method according to claim 54, CHARACTERIZED in that twice-daily administration of a 3 mg dose of upadacitinib, twice-daily administration of a 4 mg dose of upadacitinib, twice-daily administration of a 6 mg dose of upadacitinib, twice-daily administration of an 8 mg dose of upadacitinib, or twice-daily administration of a 12 mg dose of upadacitinib occurs to the pediatric patient as a stable oral pharmaceutical solution.

56. Method according to claim 55, CHARACTERIZED in that the stable oral pharmaceutical solution comprises upadacitinib, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

57. Method according to claim 55 or 56, CHARACTERIZED in that the oral solution comprises upadacitinib at a concentration of about 0.5 mg / mL or about 1 mg / mL. Petition 870250084429, dated 19 / 09 / 2025, pp. 169 / 189 17 / 19 58. Method according to claim 54, CHARACTERIZED in that once-daily administration of a 15 mg dose of upadacitinib or once-daily administration of a 30 mg dose of upadacitinib is performed on the pediatric patient as a prolonged-release tablet.

59. Stable oral pharmaceutical solution, CHARACTERIZED by comprising upadacitinib or a pharmaceutically acceptable salt or solid form thereof, a buffer and / or pH adjusting agent, a preservative, a sweetener and water.

60. Stable oral pharmaceutical solution, according to claim 59, CHARACTERIZED by comprising the anhydrous free base of upadacitinib at a concentration of about 0.5 mg / mL.

61. Stable oral pharmaceutical solution, according to claim 59, CHARACTERIZED by comprising the anhydrous free base of upadacitinib at a concentration of about 1 mg / mL.

62. Stable oral pharmaceutical solution according to claim 59, CHARACTERIZED in that the buffer is selected from the group consisting of citrate, phosphate, tartrate, succinate, formate, acetate and combinations thereof.

63. Stable oral pharmaceutical solution according to claim 59, CHARACTERIZED in that the pH adjusting agent is selected from the group consisting of citric acid, phosphoric acid, tartaric acid, succinic acid, formic acid, acetic acid and combinations thereof.

64. Stable oral pharmaceutical solution, according to claim 59, CHARACTERIZED in that the preservative is selected from the group consisting of sodium benzoate, benzoic acid, propylparaben, sodium metabisulfite, potassium sorbate, hydroxyparabenzoic acid, hydroxyparabenzoate and combinations thereof.

65. Stable oral pharmaceutical solution, according to claim 59, CHARACTERIZED in that the sweetener is selected from the group consisting of cralose, acesulfame potassium, sodium saccharin, neotame, sucrose, maltitol, xylitol and combinations thereof. Petition 870250084429, dated 09 / 19 / 2025, pages 170 / 189 18 / 19 66. Stable oral pharmaceutical solution, according to claim 59, CHARACTERIZED by comprising anhydrous free base of upadacitinib, citric acid, sodium citrate, sodium benzoate, sucralose and water.

67. Stable oral pharmaceutical solution according to claim 59, the stable oral pharmaceutical solution being CHARACTERIZED by having a pH in a range of about 2 to about 5.

68. Stable oral pharmaceutical solution according to claim 59, the stable oral pharmaceutical solution being CHARACTERIZED by having a pH in a range of about 3 to about 4.

69. Stable oral pharmaceutical solution, according to claim 59, the stable oral pharmaceutical solution being CHARACTERIZED by having a pH in a range of about 2.5 to about 3.

5.

70. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response of 30 in 24 weeks after the first daily administration.

71. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR 50 response in 24 weeks after the first daily administration.

72. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response 70 within 24 weeks after the first daily administration.

73. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response of 90 within 24 weeks after the first daily administration.

74. Method, according to any one of claims 1 to 4, Petition 870250084429, dated 09 / 19 / 2025, pp. 171 / 189 19 / 19 CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response 30 in 48 weeks after the first daily administration.

75. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR 50 response in 48 weeks after the first daily administration.

76. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response 70 in 48 weeks after the first daily administration.

77. Method, according to any one of claims 1 to 4, CHARACTERIZED by the pediatric patient achieving a pediatric JIA ACR response of 90 within 48 weeks after the first daily administration. Petition 870250084429, dated 09 / 19 / 2025, pp. 172 / 189

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