PHARMACEUTICAL COMPOSITIONS OF ANTI-IGF-1R ANTIBODIES
Provided herein are pharmaceutical compositions of anti-IGF-1R antibodies and uses thereof.
1 . A stable formulation comprising an anti-IGF-1R antibody or antigen-binding fragment thereof at a concentration of 25-250 mg/ml,
wherein the antibody comprises a heavy chain variable region comprising HCDR1 of SEQ ID NO: 53, an HCDR2 of SEQ ID NO: 54, an HCDR3 of SEQ ID NO: 55, a light chain variable region comprising a LCDR1 of SEQ ID NO: 56, a LCDR2 of SEQ ID NO: 57 and a LCDR3 of SEQ ID NO: 58, and
wherein the formulation has a pH of 4.8-6.5.
2 . The stable formulation of claim 1 , wherein the heavy chain variable region is at least 90% identical to SEQ ID NO: 14 and the light chain variable region is at least 90% identical to SEQ ID NO: 13.
3 . (canceled)
4 . The stable formulation of claim 1 , wherein the antibody comprises a heavy chain of SEQ ID NO: 92 or SEQ ID NO: 94, and a light chain of SEQ ID NO: 93.
5 . The stable formulation of claim 1 , wherein the anti-IGF-1R antibody is present at a concentration of between 25-200 mg/ml, 50-200 mg/ml, 75-180 mg/ml, or 100-150 mg.
6 - 7 . (canceled)
8 . The stable formulation of claim 1 , wherein the pH is between 5.0-6.0, 5.2-6.0 or 5.2-6.5.
9 . (canceled)
10 . The stable formulation of claim 1 , wherein the formulation further comprises sucrose.
11 - 12 . (canceled)
13 . The stable formulation of claim 1 , wherein the formulation further comprises a stabilizer.
14 - 16 . (canceled)
17 . The stable formulation of claim 1 , wherein the composition further comprises a surfactant.
18 - 21 . (canceled)
22 . The stable formulation of claim 1 , wherein the formulation further comprises a buffering agent.
23 - 25 . (canceled)
26 . The stable formulation of claim 1 , wherein the buffering agent does not comprise succinate.
27 . A stable formulation comprising:
an anti-IGF-1R antibody comprising at a concentration of 50 mg/ml;
a histidine buffer at concentration of 20 mM;
methionine at a concentration of 10 mM;
polysorbate 80 at a concentration of 0.02% (w/v);
sucrose at a concentration of 8% (w/v); and
pH of 5.5;
wherein the antibody comprises an HCDR1 of SEQ ID NO: 53, a HCDR2 of SEQ ID NO: 54, an HCDR3 of SEQ ID NO: 55, a LCDR1 of SEQ ID NO: 56, a LCDR2 of SEQ ID NO: 57 and a LCDR3 of SEQ ID NO: 58.
28 . A stable formulation comprising:
an anti-IGF-1R antibody comprising at a concentration of 150 mg/ml;
a histidine buffer at concentration of 20 mM;
methionine at a concentration of 10 mM;
polysorbate 80 at a concentration of 0.04% (w/v);
sucrose at a concentration of 8% (w/v); and
pH of 5.5;
wherein the antibody comprises an HCDR1 of SEQ ID NO: 53, an HCDR2 of SEQ ID NO: 54, an HCDR3 of SEQ ID NO: 55, a LCDR1 of SEQ ID NO: 56, a LCDR2 of SEQ ID NO: 57 and a LCDR3 of SEQ ID NO: 58.
29 . The stable formulation of claim 1 , wherein antibody comprises a heavy chain variable region that is at least 90% identical to SEQ ID NO: 14 and a light chain variable region that is at least 90% identical to SEQ ID NO: 13.
30 . (canceled)
31 . The stable formulation of claim 1 , wherein anti-IGF-1R antibody comprises a heavy chain comprising SEQ ID NO: 92, and a light chain comprising SEQ ID NO: 93.
32 . (canceled)
33 . The stable formulation of claim 1 , wherein less than 5%, less than 4%, less than 3%, less than 2.5%, less than 2%, or less than 1.5% of the IGF-1R antibody exists as HMW species in the formulation upon storage at 40° C. for at least 4 weeks.
34 - 44 . (canceled)
45 . The stable formulation of claim 1 , wherein the osmolality is between 280-380 mOsmol/kg or between 340-420 mOsmol/kg.
46 . The stable formulation of claim 1 , wherein the formulation is stored at 25 to 25° C.
47 . (canceled)
48 . The stable formulation of claim 1 , wherein the formulation is suitable for intravenous, subcutaneous, or intramuscular administration.
49 - 50 . (canceled)
51 . A method of treating thyroid associated ophthalmopathy in a subject comprising administering the stable formulation of claim 1 .
52 - 55 . (canceled)
56 . A method of treating or reducing the severity of thyroid-associated ophthalmopathy (TAO) in a subject comprising administering the stable formulation of claim 1 ,
wherein treatment with said pharmaceutical composition reduces proptosis by at least 2 mm in an eye; or
is not accompanied by a deterioration of 2 mm or more in the other (or fellow eye); and/or
reduces the CAS in said subject to either one (1) or zero (0).
57 - 64 . (canceled)