Use of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4h)-yl)piperidine-2,6-dione in treatment of immune-related and inflammatory diseases

Abstract

Provided herein are methods of using compounds and compositions for modulating lymphocytic activity, including activity of B cells and/or T cells, in immune-related diseases or inflammatory diseases. Pharmaceutical compositions and dosing regimens for use in the methods are also provided herein.

1 . A method for treating, preventing or managing an immune-related disease or an inflammatory disease comprising administering to a patient in need thereof an effective amount of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer, racemic mixture, co-crystal, clathrate, or polymorph thereof. 
     
     
         2 . The method of  claim 1 , wherein the disease is systemic lupus erythematosus, scleroderma, Sjögren syndrome, ANCA-induced vasculitis, anti-phospholipid syndrome or myasthenia gravis. 
     
     
         3 . The method of  claim 1 , wherein the disease is systemic lupus erythematosus. 
     
     
         4 . The method of  claim 1 , wherein the disease is severe systemic lupus erythematosus. 
     
     
         5 . The method of  claim 1 , wherein the disease is scleroderma. 
     
     
         6 . The method of  claim 5 , wherein the scleroderma is localized, systemic, limited or diffuse scleroderma. 
     
     
         7 . The method of  claim 6 , wherein the systemic scleroderma comprises CREST syndrome. 
     
     
         8 . A method for reducing, inhibiting or preventing a symptom of systemic lupus erythematosus comprising administering an effective amount of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof to a patient having the symptom of systemic lupus erythematosus, wherein the symptom is selected from the group consisting of joint pain, joint swelling, arthritis, chest pain when taking a deep breath, fatigue, fever with no other cause, general discomfort, uneasiness, hair loss, mouth sores, swollen lymph nodes, sensitivity to sunlight, skin rash, headaches, numbness, tingling, seizures, vision problems, personality changes, abdominal pain, nausea, vomiting, abnormal heart rhythms, coughing up blood and difficulty breathing, patchy skin color and Raynaud's phenomenon. 
     
     
         9 . A method for reducing, inhibiting or preventing a symptom of scleroderma comprising administering to a patient having the symptom of scleroderma an effective amount of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer, racemic mixture, co-crystal, clathrate, or polymorph thereof, wherein the symptom is selected from the group consisting of (i) gradual hardening, thickening, and tightening of the skin; (ii) skin discoloration; (iii) numbness of extremities; (iv) shiny skin; (v) small white lumps under the surface of the skin that erupt into a chalky white fluid; (vi) Raynaud's esophagaeal dysfunction; (vii) telangiectasia; (viii) pain and/or stiffness of the joints; (ix) swelling of the hands and feet; (x) itching of the skin; (xi) stiffening and curling of the fingers; (xii) ulcers on the outside of certain joints, such as knuckles and elbows; (xiii) digestive problems, such as heartburn, difficulty in swallowing, diarrhea, irritable bowel, and constipation; (xiv) fatigue and weakness; (xv) shortness of breath; (xvi) arthritis; (xvii) hair loss; (xviii) internal organ problems; (xix) digital ulcers; and (xx) digital auto-amputation. 
     
     
         10 . A method for improving the modified Rodnan skin score, reducing or improving the skin thickness, reducing or improving skin induration, improving the pulmonary function, improving the dermatology quality of life index, improving the carbon monoxide diffusing capacity, improving the Mahler Dyspnea index, improving the Saint George's Respiratory Questionnaire score, improving the UCLA scleroderma clinical trial consortium gastrointestinal tract score, improving flow-mediated dilatation or improving or increasing the six minute walk distance of a patient having scleroderma, comprising administering to the patient an effective amount of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer, racemic mixture, co-crystal, clathrate, or polymorph thereof. 
     
     
         11 . The method of  claim 1  further comprising administering a second active agent, wherein the second active agent is an anti-inflammatory or immunomodulatory compound. 
     
     
         12 . The method of  claim 1 , wherein the effective amount is about 0.005 mg/kg to about 10 mg/kg of the patient's body weight. 
     
     
         13 . A method for modulating activity of a B cell comprising contacting the cell with an effective amount of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione or a pharmaceutically acceptable salt, solid form, solvate, hydrate, stereoisomer, tautomer, racemic mixture, co-crystal, clathrate, or polymorph thereof thereof. 
     
     
         14 . A method for modulating activity of a T cell comprising contacting the cell with an effective amount of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione or a pharmaceutically acceptable salt, solid form, solvate, hydrate, tautomer, stereoisomer, racemic mixture, co-crystal, clathrate, or polymorph thereof thereof. 
     
     
         15 . The method of  claim 8  further comprising administering a second active agent, wherein the second active agent is an anti-inflammatory or immunomodulatory compound. 
     
     
         16 . The method of  claim 8 , wherein the effective amount is about 0.005 mg/kg to about 10 mg/kg of the patient's body weight. 
     
     
         17 . The method of  claim 9  further comprising administering a second active agent, wherein the second active agent is an anti-inflammatory or immunomodulatory compound. 
     
     
         18 . The method of  claim 9 , wherein the effective amount is about 0.005 mg/kg to about 10 mg/kg of the patient's body weight. 
     
     
         19 . The method of  claim 10  further comprising administering a second active agent, wherein the second active agent is an anti-inflammatory or immunomodulatory compound. 
     
     
         20 . The method of  claim 10 , wherein the effective amount is about 0.005 mg/kg to about 10 mg/kg of the patient's body weight.