Compositions, doses, and methods for treatment of thyroid eye disease

Abstract

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

1 . A method of treating thyroid associated ophthalmopathy in a subject in need thereof, comprising:
 intravenously or subcutaneously administering a first dose, wherein the first dose is selected from the group consisting of: about 1 mg/kg to about 2 mg/kg, about 2 mg/kg to about 5 mg/kg, about 3 mg/kg to about 5 mg/kg, about 5 mg/kg to about 7.5 mg/kg, about 7.5 mg/kg to about 10 mg/kg, about 10 mg/kg to about 15 mg/kg, or about 15 mg/kg to about 20 mg/kg, of an antibody to the subject; and   intravenously or subcutaneously administering one or more subsequent doses, wherein each subsequent dose is selected from the group consisting of: about 1 mg/kg to about 2 mg/kg, about 2 mg/kg to about 5 mg/kg, about 3 mg/kg to about 5 mg/kg, about 5 mg/kg to about 7.5 mg/kg, about 7.5 mg/kg to about 10 mg/kg, about 10 mg/kg to about 15 mg/kg, or about 15 mg/kg to about 20 mg/kg of the antibody to the subject,   wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6.   
     
     
         2 - 21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the treated subject's proptosis is reduced by at least, or about, 1-4 mm. 
     
     
         23 . The method of  claim 22 , wherein the proptosis is reduced by at least, or about 2-3 mm. 
     
     
         24 . The method of  claim 22 , wherein the proptosis is reduced within 3 weeks of the first dose. 
     
     
         25 . The method of  claim 22 , wherein the proptosis is reduced within 6 weeks of the first dose. 
     
     
         26 . The method of  claim 1 , wherein the treated subject has reduced diplopia. 
     
     
         27 . The method of  claim 26 , wherein the diplopia is reduced within 3 weeks or 6 weeks of the first dose. 
     
     
         28 . The method of  claim 1 , wherein the subject has an improvement in Clinical Activity Score (CAS) within 3 weeks or 6 weeks. 
     
     
         29 . The method of  claim 28 , wherein the CAS score has an improvement of at least −2, −3, or −4. 
     
     
         30 . The method of  claim 1 , wherein the subject has a reduction in proptosis and an improvement in CAS score within 3 weeks or within 6 weeks of the first dose. 
     
     
         31 . A method of treating thyroid associated ophthalmopathy in a subject in need thereof, comprising:
 intravenously administering a dose of 10 mg/kg of an anti-IGF-1R antibody to the subject at a regular interval for a period sufficient to reduce one or more symptoms associated with thyroid associated ophthalmopathy,   wherein the anti-IGF-1R antibody comprises a heavy chain com a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and a light chain comprising a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6.   
     
     
         32 . The method of  claim 31 , wherein the anti-IGF-1R antibody comprises a light chain and a heavy chain, wherein the light chain comprises a variable region having the amino acid sequence of SEQ ID NO: 2 and the heavy chain comprises a variable region having the amino acid sequence of SEQ ID NO: 3. 
     
     
         33 . The method of  claim 31 , wherein the light chain comprises an amino acid sequence of SEQ ID NO: 11. 
     
     
         34 . The method of  claim 31 , wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 10. 
     
     
         35 . The method of  claim 31 , wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 10 and the light chain comprises an amino acid sequence of SEQ ID NO: 11. 
     
     
         36 . The method of  claim 31 , wherein the anti-IGF-1R antibody is administered by intravenous infusion. 
     
     
         37 . The method of  claim 31 , wherein the anti-IGF-1R antibody is administered every 3 weeks. 
     
     
         38 . The method of  claim 31 , wherein the anti-IGF-1R antibody is administered for a period sufficient for 5 doses. 
     
     
         39 . The method of  claim 31 , wherein the anti-IGF-1R antibody is administered for a period sufficient for 8 doses. 
     
     
         40 . The method of  claim 31 , wherein the anti-IGF-1R antibody is administered for a period selected from 3 weeks, 6 weeks, 9 weeks, 12 weeks, 15 weeks, 18 weeks, 21 weeks, 24 weeks or longer. 
     
     
         41 - 49 . (canceled)