COMPOSITIONS, DOSES, AND METHODS FOR TREATMENT OF THYROID EYE DISEASE
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)