US2021253719A1PendingUtilityA1

Methods for the treatment of thyroid eye disease

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Assignee: HZNP LTDPriority: Aug 28, 2019Filed: Mar 3, 2021Published: Aug 19, 2021
Est. expiryAug 28, 2039(~13.1 yrs left)· nominal 20-yr term from priority
Inventors:Jeffrey W. ShermanDennis A. BennettSrini RamanathanYan XinElizabeth ThompsonElizabeth O'Neill
A61K 2039/55A61K 31/5377C07K 2317/56A61K 31/517A61P 27/02C07K 2317/76A61K 31/4985C07K 16/2863A61K 2039/505A61K 31/277A61K 31/506A61K 2039/545A61K 31/53A61K 31/365C07K 2317/565A61K 31/519A61K 39/3955A61K 31/4545
46
PatentIndex Score
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Claims

Abstract

Provided herein are methods of treating or reducing the severity of thyroid eye disease (TED), also known as thyroid-associated ophthalmopathy (TAO), or Graves' ophthalmopathy or orbitopathy (GO), as well as antibodies, or antigen binding fragments thereof, and pharmaceutical compositions comprising them, useful in the methods.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of treating thyroid eye disease (TED) in a subject with TED, comprising administering to the subject a therapeutically effective amount of an antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30. 
     
     
         2 . The method of  claim 1 , wherein the antibody comprises a heavy chain variable domain comprising SEQ ID NOs:31 or 78 or 79, and a light chain variable domain comprising SEQ ID NOs:32 or 80 or 81 or 82 or 83. 
     
     
         3 . The method of  claim 2 , wherein the antibody comprises a heavy chain variable domain comprising SEQ ID NO:78 and a light chain variable domain comprising SEQ ID NOs:80 or 81 or 82 or 83. 
     
     
         4 . The method of  claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:80. 
     
     
         5 . The method of  claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:81. 
     
     
         6 . The method of  claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:82. 
     
     
         7 . The method of  claim 3 , wherein the antibody comprises the light chain variable domain comprising SEQ ID NO:83. 
     
     
         8 . The method of  claim 1 , wherein the therapeutically effective amount comprises a dosage of 1-60 mg/kg or 75-4500 mg IV Q3W; or 0.6-40 mg/kg or 45-3000 mg IV Q2W; or 0.3-20 mg/kg or 22-1500 mg IV QW. 
     
     
         9 . A method of reducing proptosis in a subject with thyroid eye disease (TED), comprising administering to the subject a therapeutically effective amount of antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30. 
     
     
         10 . The method of  claim 9 , wherein the therapeutically effective amount comprises a dosage of 1-60 mg/kg or 75-4500 mg IV Q3W; or 0.6-40 mg/kg or 45-3000 mg IV Q2W; or 0.3-20 mg/kg or 22-1500 mg IV QW. 
     
     
         11 . The method of  claim 9 , wherein proptosis is reduced by at least 2 mm. 
     
     
         12 . The method of  claim 11 , wherein proptosis is reduced by at least 3 mm. 
     
     
         13 . The method of  claim 12 , wherein proptosis is reduced by at least 4 mm. 
     
     
         14 . The method of  claim 9 , wherein the method additionally comprises reducing the clinical activity score (CAS) in the subject with TED. 
     
     
         15 . The method of  claim 14 , wherein CAS is reduced by at least 2 points. 
     
     
         16 . The method of  claim 15 , wherein CAS is reduced by at least 3 points. 
     
     
         17 . The method of  claim 14 , wherein proptosis is reduced by at least 3 mm and CAS is reduced by at least 3 points. 
     
     
         18 . A method of treating or reducing the severity of diplopia in a subject with thyroid eye disease (TED), comprising administering to the subject a therapeutically effective amount of antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30. 
     
     
         19 . The method of  claim 18 , wherein the diplopia is constant diplopia. 
     
     
         20 . The method of  claim 18 , wherein the diplopia is intermittent diplopia. 
     
     
         21 . The method of  claim 18 , wherein the diplopia is inconstant diplopia. 
     
     
         22 . The method of  claim 18 , wherein the improvement in or reduction in severity of diplopia is sustained at least 20 weeks after discontinuation of inhibitor administration. 
     
     
         23 . The method of any of  claim 22 , wherein the improvement in or reduction in severity of diplopia is sustained at least 50 weeks after discontinuation of inhibitor administration. 
     
     
         24 . A method of reducing Clinical Activity Score (CAS) of thyroid eye disease (TED) in a subject with TED, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO:25, a HCDR2 comprising the amino acid sequence of SEQ ID NO:76, a HCDR3 comprising the amino acid sequence of SEQ ID NO:27, a LCDR1 comprising the amino acid sequence of SEQ ID NO:28, a LCDR2 comprising the amino acid sequence of SEQ ID NO:29, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:30. 
     
     
         25 . The method of  claim 1 , wherein the therapeutically effective amount comprises a dosage of 1-10 mg/kg. 
     
     
         26 . The method of  claim 25 , wherein the therapeutically effective amount comprises a dosage of 1-5 mg/kg. 
     
     
         27 . The method of  claim 26 , wherein the therapeutically effective amount comprises a dosage of about 2 mg/kg, about 3 mg/kg, about 4 mg/kg, or about 5 mg/kg. 
     
     
         28 . The method of  claim 26 , wherein the therapeutically effective amount is administered every 1, 2, 3, 4, or 5 weeks (i.e., QW, Q2W, Q3W, Q4W, or Q5W). 
     
     
         29 . The method of  claim 28 , wherein the therapeutically effective amount is administered intravenously (IV) or subcutaneously (SC). 
     
     
         30 . The method of  claim 1 , wherein the therapeutically effective amount comprises a dosage of 1-5 mg/kg or 75-375 mg IV Q3W; or 0.6-4 mg/kg or 45-300 mg IV Q2W; or 0.3-3 mg/kg or 22-225 mg IV QW.

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