Compositions and methods for treatment of thyroid eye disease

Abstract

Antibodies and compositions against IGF-1R and uses thereof are provided herein.

1 - 47 . (canceled) 
     
     
         48 . A pharmaceutical composition comprising an antibody for treating thyroid eye disease in a subject, wherein the antibody comprises: a light chain variable region having the amino acid sequence of SEQ ID NO: 13; a heavy chain variable region having the amino acid sequence of SEQ ID NO: 14; and a Fc region comprising a M428L and N434S substitutions and/or M252Y, S254T, and T256E substitutions. 
     
     
         49 . The pharmaceutical composition of  claim 48 , wherein the antibody comprises a Fc region with M428L and N434S substitutions. 
     
     
         50 . The pharmaceutical composition of  claim 48 , wherein the antibody comprises a Fc region with M252Y, S254T, and T256E substitutions. 
     
     
         51 . A method of treating thyroid eye disease in a subject, the method comprising administering the pharmaceutical composition comprising the antibody of  claim 48 . 
     
     
         52 . The method of  claim 51 , wherein the pharmaceutical composition is administered intravenously or subcutaneously. 
     
     
         53 . A method of treating thyroid eye disease in a subject, the method comprising administering the pharmaceutical composition comprising the antibody of  claim 49 . 
     
     
         54 . The method of  claim 53 , wherein the pharmaceutical composition is administered subcutaneously or intravenously. 
     
     
         55 . A method of treating thyroid eye disease in a subject, the method comprising administering the pharmaceutical composition comprising the antibody of  claim 50 . 
     
     
         56 . A method of treating or reducing the severity of, thyroid-associated ophthalmopathy (TAO), or a symptom thereof, the method comprising administering to a subject the pharmaceutical composition of  claim 48 . 
     
     
         57 . A method of treating or reducing the severity of, thyroid-associated ophthalmopathy (TAO), or a symptom thereof, the method comprising administering to a subject the pharmaceutical composition of  claim 49 . 
     
     
         58 . A method of reducing proptosis in an eye in a subject with thyroid-associated ophthalmopathy (TAO), the method comprising administering to a subject the pharmaceutical composition of  claim 48 . 
     
     
         59 . A method of reducing proptosis in an eye in a subject with thyroid-associated ophthalmopathy (TAO), the method comprising administering to a subject the pharmaceutical composition of  claim 49 . 
     
     
         60 . A method of reducing Clinical Activity Score (CAS) of thyroid-associated ophthalmopathy (TAO) in a subject, the method comprising administering to a subject the pharmaceutical composition of  claim 48 . 
     
     
         61 . A method of reducing Clinical Activity Score (CAS) of thyroid-associated ophthalmopathy (TAO) in a subject, the method comprising administering to a subject the pharmaceutical composition of  claim 49 . 
     
     
         62 . A method of a) reducing proptosis by at least 2 mm and b) reducing the clinical activity score (CAS) in a subject with thyroid-associated ophthalmopathy (TAO), the method comprising administering to a subject the pharmaceutical composition of  claim 48 . 
     
     
         63 . A method of a) reducing proptosis by at least 2 mm and b) reducing the clinical activity score (CAS) in a subject with thyroid-associated ophthalmopathy (TAO), the method comprising administering to a subject the pharmaceutical composition of  claim 49 . 
     
     
         64 . A method of treating or reducing the severity of diplopia in a subject with thyroid-associated ophthalmopathy (TAO), the method comprising administering to a subject the pharmaceutical composition of  claim 48 . 
     
     
         65 . A method of treating or reducing the severity of diplopia in a subject with thyroid-associated ophthalmopathy (TAO), the method comprising administering to a subject the pharmaceutical composition of  claim 49 . 
     
     
         66 . The method of  claim 51 , wherein said pharmaceutical composition is administered at a dosage of about 1 μg/kg to about 5 μg/kg, about 5 μg/kg to about 10 μg/kg, about 10 μg/kg to about 20 μg/kg, about 20 μg/kg to about 30 μg/kg, about 5 μg/kg, about 10 μg/kg, about 15 μg/kg, about 20 μg/kg, about 25 μg/kg, or about 30 μg/kg of the antibody as a first dose. 
     
     
         67 . A method of treating thyroid eye disease in a subject, the method comprising administering the pharmaceutical composition of  claim 48  to the subject, wherein the antibody has a serum concentration in the subject of at least, or about, 10 μg/ml or 20 μg/ml or 50 μg/ml, 70 μg/ml, 75 μg/ml, 80 μg/ml, 85 μg/ml, 90 μg/ml, 95 μg/ml, 100 μg/ml, or 105 μg/ml at least 1, 2, or 3 weeks after administration.