Usage and dosage of therapeutic agents for endometriosis
Inventors
Dan, Takuro • Takahashi, Hideomi • Kuramochi, Yu
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11382914-B2
Publication Date
2022-07-12
Expiration Date
Abstract
An object of the present invention is to provide pharmaceutical agents that reduce risk for decrease in bone mineral density due to their effect of reducing estrogen levels and exert excellent therapeutic effects on endometriosis. The present invention relates to pharmaceutical compositions for treating endometriosis comprising 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid or a pharmaceutically acceptable salt thereof, which are administered orally once a day at a daily dose of between 50 mg and 75 mg calculated as a free form.
Core Innovation
The patent describes pharmaceutical compositions and methods for treating endometriosis using 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid (Compound 1) or pharmaceutically acceptable salts thereof, including a choline salt (Compound 2). The disclosed approach is framed around a reduction of estrogen (E2) while addressing risk of bone mineral density decrease, and relates efficacy and side effects to E2 levels.
The problem addressed is menstrual pain due to endometriosis in a human patient in need thereof, and the associated pathophysiology driven by estrogen secretion. The background framing includes managing endometriosis-associated pain while avoiding adverse effects associated with hypoestrogenism, including maintaining an estrogen therapeutic window.
The disclosed methods include administering Compound 1 or its pharmaceutically acceptable salt in an amount of 75 mg calculated as a free form per day, with oral and once-daily administration described in embodiments. The document reports clinical-trial results showing improvements in pelvic pain and other endometriosis outcomes versus placebo, alongside reduced hypoestrogenism side effects at E2 levels at or below a specified threshold.
Claims Coverage
Two independent methods are covered. Across both independent claims, the same specific thieno[3,4-d]pyrimidine-5-carboxylic acid compound (Compound 1) or a pharmaceutically acceptable salt is administered at a specified daily amount calculated as a free form, with dependent claims focusing on salt form, oral administration, and once-daily dosing.
Reducing menstrual pain due to endometriosis using a 75 mg daily dose of the named compound
A method of reducing menstrual pain due to endometriosis in a human patient in need thereof by administering 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof, wherein the compound is administered in an amount of 75 mg, calculated as a free form, per day.
Reducing estrogen secretion in endometriosis using a 75 mg daily dose of the named compound
A method of reducing estrogen secretion in a human patient having endometriosis by administering 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof, wherein the compound is administered in an amount of 75 mg, calculated as a free form, per day.
The independent claim set covers reducing menstrual pain due to endometriosis and reducing estrogen secretion in patients with endometriosis, both via administration of the same specified compound (or a pharmaceutically acceptable salt) at a daily dose of 75 mg calculated as a free form, with dependent claims specifying administration details such as oral and once-daily dosing and particular salt forms (including a choline salt).
Stated Advantages
Improved pelvic pain (NRS) and other endometriosis outcomes versus placebo.
Reduced hypoestrogenism side effects at E2 levels at or below a specified threshold (E2 ≤ 20 pg/mL).
A dosing comparison indicates similar analgesic efficacy with reduced hypoestrogenism at 50 mg compared with higher doses (100–200 mg).
An efficacy/side-effect balance is achieved by reducing estrogen (E2) while lowering risk of bone mineral density loss using an estrogen therapeutic-window approach.
Documented Applications
Treating endometriosis in a human patient, including reducing menstrual pain due to endometriosis and reducing estrogen secretion in patients having endometriosis.
Endometriosis-associated pain management as evidenced by improvements in pelvic pain scores (NRS) and other endometriosis outcomes versus placebo.
Interested in licensing this patent?