Pharmaceutical compositions of anti-igf-1r antibodies

Abstract

Provided herein are pharmaceutical compositions of anti-IGF-1R antibodies and uses thereof.

Description

Cross-reference of related applications

[0001] This application claims priority to International Application No. PCT / CN2023 / 117341, filed on September 6, 2023, and Chinese Application No. 202411218553.4, filed on August 30, 2024, each of which is incorporated herein by reference in its entirety.

[0002] Reference to the sequence listing submitted electronically This application contains a sequence list, which is electronically submitted in XML file format and incorporated herein by reference in its entirety. The XML copy was created on September 5, 2024, named “VRD-010WO1_SL.xml”, and is 102,012 bytes in size. Background Technology

[0003] Advances in biotechnology have made it possible to generate numerous monoclonal antibodies for pharmaceutical applications. Antibodies are larger and more complex than traditional organic and inorganic drugs, and the formulation of antibodies for therapeutic use presents specific challenges. One such challenge is maintaining antibody stability, which is crucial for ensuring product quality. Another challenge is viscosity when formulating antibodies for therapeutic use, especially when formulating high-concentration antibodies. The unique amino acid sequence and three-dimensional structure of antibodies cause variations in physicochemical properties (such as isoelectric point, hydrophobicity, and surface charge distribution), which can be difficult to predict and significantly affect the behavior of the formulated antibody. The optimal pH, ionic strength, buffer type, and excipients required for stabilization vary based on the specific structural characteristics of each antibody, and "one-size-fits-all" formulations are not feasible.

[0004] Thyroid-associated ophthalmopathy (TAO) (also known as thyroid eye disease (TED), Graves' ophthalmopathy, or orbital lesions (GO), thyrotoxic exophthalmos, thyroid dysfunctional ophthalmopathy, and several other terms) is an orbital lesion associated with thyroid dysfunction. TAO is classified into two types: active TAO and inactive TAO. Active TAO, which typically lasts 1–3 years, is characterized by a persistent autoimmune / inflammatory response in the orbital soft tissues. Active TAO causes expansion and remodeling of the ocular soft tissues. The autoimmune / inflammatory response of active TAO resolves spontaneously, and the disease transforms into inactive TAO. Inactive TAO is the term used to describe the long-term / permanent sequelae of active TAO. The etiology of TAO is unknown. Trans-orbital thyroid angina (TAO) is commonly associated with Graves' hyperthyroidism but can also occur as part of other autoimmune disorders affecting the thyroid gland, and can cause lesions in the orbit and periorbital tissues and, rarely, the pretibial skin (pretibial myxedema) or fingers (thyroid clubbing). TAO is an autoimmune orbital disorder that primarily affects the orbit and periorbital soft tissues, and has secondary effects on the eye and vision. In TAO, inflammation and expansion of the orbital soft tissues (mainly the eye muscles and fat) force the eye forward (protrudes) out of its socket—a phenomenon known as ptosis or exophthalmos. Although most TAOs do not cause visual loss, the disorder can cause visually threatening exposure keratopathy, troublesome diplopia (binovision), and compressive thyroid-related optic neuropathy. TAO can occur before, during, or after systemic complications of thyroid dysfunction. The ocular manifestations of TAO include upper eyelid retraction, eyelid lag, swelling, redness (erythema), conjunctivitis, and bulging of the eye (protruding eyeballs or exophthalmos), conjunctival edema, periorbital edema, and changes in eye movement, all of which can have significant functional, social, and cosmetic impacts. Many signs and symptoms of TAO (including exophthalmos and ocular hyperemia) arise from the expansion of orbital adipose tissue and periorbital muscles. The increase in adipose tissue volume is partly due to the development of new adipocytes within the orbital fat (adipogenesis). The accumulation of hydrophilic glycosaminoglycans (primarily hyaluronic acid) in the perimysial connective tissue between the orbital adipose tissue and extraocular muscle fibers further expands the fat compartments and the extraocular muscle body. Hyaluronic acid is produced by fibroblasts residing in the orbital fat and extraocular muscles, and its in vitro synthesis is stimulated by several cytokines and growth factors, including IL-1β, interferon-γ, platelet-derived growth factor, thyroid-stimulating hormone (TSH), and insulin-like growth factor I (IGF-I).

[0005] Antibodies activating insulin-like growth factor I receptor (IGF-IR) have also been detected and are associated with active TAO. relatedUnrestricted by any particular theory, it is believed that TSHR and IGF-IR form a physical and functional complex in orbital fibroblasts, and that blocking IGF-IR appears to attenuate IGF-1 and TSH-dependent signaling. It has been shown that blocking IGF-IR with antibody antagonists reduces TSHR- and IGF-I-dependent signaling, thereby disrupting the pathological activity of autoantibodies acting as any receptor agonists.

[0006] IGF-IR is a widely expressed heterotetrameric protein involved in regulating proliferation and metabolic functions in many cell types. It is a tyrosine kinase receptor containing two subunits. IGF-IRα contains a ligand-binding domain, while IGF-IRβ is involved in signal transduction and contains a tyrosine phosphorylation site.

[0007] Current treatments for hyperthyroidism caused by Graves' disease are imperfect due to the lack of therapies targeting the specific underlying autoimmune mechanisms of the disease. Treatment of moderate to severe active TAO is even more complex. Despite a better understanding of its pathogenesis in recent years, TAO remains a therapeutic challenge and dilemma. Intravenous glucocorticoids (ivGC) and oral glucocorticoids are used to treat patients with moderate to severe active TAO, but results are rarely satisfactory. Frequent partial responses and relapses (rebound) after drug withdrawal are not uncommon. Adverse events do occur, and many patients eventually require rehabilitative surgery when the condition progresses to inactive TAO. Therefore, alternative therapies for TAO and its associated symptoms remain needed. Summary of the Invention

[0008] This invention provides, in particular, stable formulations of anti-insulin-like growth factor 1 receptor (IGF-1R) antibodies, especially those described herein, suitable for intravenous, subcutaneous, and other routes of administration. The invention is based in part on the discovery of a specific pH range (i.e., 4.8–6.5 and especially 4.8–6.0) that imparts conformational and colloidal stability to the antibodies in the formulation. Therefore, this invention allows for the formulation of anti-IGF-1R antibodies, especially those described herein, at high concentrations and with high purity and long-term stability, thereby enabling safer and more effective clinical use.

[0009] In one aspect, the present invention particularly provides a stable formulation comprising an anti-IGF-1R antibody or an 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, HCDR2 of SEQ ID NO: 54, and HCDR3 of SEQ ID NO: 55, and a light chain variable region comprising LCDR1 of SEQ ID NO: 56, LCDR2 of SEQ ID NO: 57, and LCDR3 of SEQ ID NO: 58, and wherein the formulation has a pH of 4.8-6.5.

[0010] In one aspect, the present invention particularly provides a stable formulation comprising an anti-IGF-1R antibody or an 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, HCDR2 of SEQ ID NO: 54, and HCDR3 of SEQ ID NO: 55, and a light chain variable region comprising LCDR1 of SEQ ID NO: 56, LCDR2 of SEQ ID NO: 57, and LCDR3 of SEQ ID NO: 58, and wherein the formulation has a pH of 4.8-6.0.

[0011] In some implementations, 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.

[0012] In some embodiments, the heavy chain variable region is at least 80% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 82% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 84% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 86% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 88% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 90% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 92% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 94% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 96% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 98% identical to SEQ ID NO: 14. In some embodiments, the heavy chain variable region is at least 99% identical to SEQ ID NO: 14.

[0013] In some embodiments, the light chain variable region is at least 80% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 82% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 84% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 86% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 88% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 90% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 92% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 94% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 96% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 98% identical to SEQ ID NO: 13. In some embodiments, the light chain variable region is at least 99% identical to SEQ ID NO: 13.

[0014] In some implementations, the heavy chain variable region contains SEQ ID NO: 14 and the light chain variable region contains SEQ ID NO: 13.

[0015] In some implementations, the antibody comprises the heavy chain of SEQ ID NO: 92 or SEQ ID NO: 94 and the light chain of SEQ ID NO: 93.

[0016] In some embodiments, the antibody comprises a heavy chain that is at least 80% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 82% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 84% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 85% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 86% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 88% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 90% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 92% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 94% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 95% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 96% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 97% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 98% identical to SEQ ID NO: 92. In some embodiments, the antibody comprises a heavy chain that is at least 99% identical to SEQ ID NO: 92.

[0017] In some embodiments, the antibody comprises a light chain that is at least 80% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 82% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 84% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 85% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 86% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 88% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 90% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 92% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 94% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 95% identical to SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 96% identical to that of SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 97% identical to that of SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 98% identical to that of SEQ ID NO: 93. In some embodiments, the antibody comprises a light chain that is at least 99% identical to that of SEQ ID NO: 93.

[0018] In some embodiments, the anti-IGF-1R antibody is present at a concentration between 25 and 200 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration between 50 and 200 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration between 25 and 75 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration between 40 and 60 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration between 100 and 200 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration between 125 and 175 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration between 140 and 160 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration between 145 and 155 mg / ml.

[0019] In some embodiments, the anti-IGF-1R antibody is present at a concentration of 25 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 50 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 60 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 70 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 75 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 100 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 125 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 150 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 175 mg / ml. In some embodiments, the anti-IGF-1R antibody is present at a concentration of 200 mg / ml.

[0020] In some embodiments, the pH is between 4.8 and 6.5. In some embodiments, the pH is between 4.8 and 6.0. In some embodiments, the pH is between 5.0 and 6.0. In some embodiments, the pH is between 5.2 and 6.0. In some embodiments, the pH is between 5.2 and 5.8.

[0021] In some embodiments, the formulation has a pH of 4.8. In some embodiments, the formulation has a pH of 4.9. In some embodiments, the formulation has a pH of 5.0. In some embodiments, the formulation has a pH of 5.1. In some embodiments, the formulation has a pH of 5.2. In some embodiments, the formulation has a pH of 5.3. In some embodiments, the formulation has a pH of 5.4. In some embodiments, the formulation has a pH of 5.5. In some embodiments, the formulation has a pH of 5.6. In some embodiments, the formulation has a pH of 5.7. In some embodiments, the formulation has a pH of 5.8. In some embodiments, the formulation has a pH of 5.9. In some embodiments, the formulation has a pH of 6.0. In some embodiments, the formulation has a pH of 6.1. In some embodiments, the formulation has a pH of 6.2. In some embodiments, the formulation has a pH of 6.3. In some embodiments, the formulation has a pH of 6.4. In some embodiments, the formulation has a pH of 6.5.

[0022] In some implementations, the formulation further comprises sucrose.

[0023] In some embodiments, sucrose is present at a concentration between 1-20% (w / v). In some embodiments, sucrose is present at a concentration between 3-15% (w / v). In some embodiments, sucrose is present at a concentration between 4-10% (w / v). In some embodiments, sucrose is present at a concentration between 6-10% (w / v). In some embodiments, sucrose is present at a concentration between 1-20% (w / v).

[0024] In some embodiments, sucrose is present at a concentration of 1% (w / v). In some embodiments, sucrose is present at a concentration of 2% (w / v). In some embodiments, sucrose is present at a concentration of 4% (w / v). In some embodiments, sucrose is present at a concentration of 5% (w / v). In some embodiments, sucrose is present at a concentration of 6% (w / v). In some embodiments, sucrose is present at a concentration of 7% (w / v). In some embodiments, sucrose is present at a concentration of 8% (w / v). In some embodiments, sucrose is present at a concentration of 9% (w / v). In some embodiments, sucrose is present at a concentration of 10% (w / v). In some embodiments, sucrose is present at a concentration of 12% (w / v). In some embodiments, sucrose is present at a concentration of 14% (w / v). In some embodiments, sucrose is present at a concentration of 16% (w / v). In some embodiments, sucrose is present at a concentration of 18% (w / v). In some implementations, sucrose is present at a concentration of 20% (w / v).

[0025] In some embodiments, the formulation further comprises a stabilizer. In some embodiments, the stabilizer is an antioxidant. In some embodiments, the stabilizer is methionine.

[0026] In some embodiments, methionine is present at a concentration between 1 and 50 mM. In some embodiments, methionine is present at a concentration between 5 and 40 mM. In some embodiments, methionine is present at a concentration between 10 and 30 mM. In some embodiments, methionine is present at a concentration between 10 and 20 mM. In some embodiments, methionine is present at a concentration between 15 and 30 mM.

[0027] In some embodiments, methionine is present at a concentration of 5 mM. In some embodiments, methionine is present at a concentration of 10 mM. In some embodiments, methionine is present at a concentration of 15 mM. In some embodiments, methionine is present at a concentration of 20 mM. In some embodiments, methionine is present at a concentration of 25 mM. In some embodiments, methionine is present at a concentration of 30 mM. In some embodiments, methionine is present at a concentration of 35 mM. In some embodiments, methionine is present at a concentration of 40 mM.

[0028] In some embodiments, the composition further comprises a surfactant.

[0029] In some embodiments, the surfactant is polysorbate 80. In some embodiments, the surfactant is polysorbate 20.

[0030] In some embodiments, polysorbate 80 is present at a concentration between 0.001 and 1% (w / v). In some embodiments, polysorbate 80 is present at a concentration between 0.005 and 0.5% (w / v). In some embodiments, polysorbate 80 is present at a concentration between 0.01 and 0.05% (w / v).

[0031] In some embodiments, polysorbate 80 is present at a concentration of 0.001% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.005% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.01% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.02% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.04% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.05% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.06% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.08% (w / v). In some embodiments, polysorbate 80 is present at a concentration of 0.1% (w / v). In some implementations, polysorbate 80 is present at a concentration of 0.2% (w / v).

[0032] In some embodiments, polysorbate 20 is present at a concentration between 0.001 and 1% (w / v). In some embodiments, polysorbate 20 is present at a concentration between 0.005 and 0.5% (w / v). In some embodiments, polysorbate 20 is present at a concentration between 0.01 and 0.05% (w / v).

[0033] In some embodiments, polysorbate 20 is present at a concentration of 0.001% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.005% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.01% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.02% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.04% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.05% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.06% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.08% (w / v). In some embodiments, polysorbate 20 is present at a concentration of 0.1% (w / v). In some implementations, polysorbate 20 is present at a concentration of 0.2% (w / v).

[0034] In some implementations, the formulation further includes a buffer.

[0035] In some embodiments, the buffer is a histidine buffer. In some embodiments, the buffer is an acetate buffer. In some embodiments, the buffer is a glutamate buffer. In some embodiments, the buffer comprises both histidine buffer and acetate buffer. In some embodiments, the buffer comprises both histidine buffer and glutamate buffer.

[0036] In some embodiments, the concentration of the buffer, alone or in combination, is between 5 and 100 mM. In some embodiments, the concentration of the buffer, alone or in combination, is between 10 and 60 mM. In some embodiments, the concentration of the buffer, alone or in combination, is between 15 and 40 mM.

[0037] In some embodiments, the concentration of histidine buffer is 5 mM. In some embodiments, the concentration of histidine buffer is 10 mM. In some embodiments, the concentration of histidine buffer is 15 mM. In some embodiments, the concentration of histidine buffer is 20 mM. In some embodiments, the concentration of histidine buffer is 25 mM. In some embodiments, the concentration of histidine buffer is 30 mM. In some embodiments, the concentration of histidine buffer is 35 mM. In some embodiments, the concentration of histidine buffer is 40 mM. In some embodiments, the concentration of histidine buffer is 45 mM. In some embodiments, the concentration of histidine buffer is 50 mM. In some embodiments, the concentration of histidine buffer is 55 mM. In some embodiments, the concentration of histidine buffer is 60 mM. In some embodiments, the concentration of histidine buffer is 65 mM. In some embodiments, the concentration of histidine buffer is 70 mM. In some embodiments, the concentration of histidine buffer is 75 mM. In some embodiments, the concentration of histidine buffer is about 80 mM. In some embodiments, the concentration of histidine buffer is 85 mM. In some embodiments, the concentration of histidine buffer is 90 mM. In some embodiments, the concentration of histidine buffer is 95 mM. In some embodiments, the concentration of histidine buffer is 100 mM.

[0038] In some embodiments, the concentration of acetate buffer is 5 mM. In some embodiments, the concentration of acetate buffer is 10 mM. In some embodiments, the concentration of acetate buffer is 15 mM. In some embodiments, the concentration of acetate buffer is 20 mM. In some embodiments, the concentration of acetate buffer is 25 mM. In some embodiments, the concentration of acetate buffer is 30 mM. In some embodiments, the concentration of acetate buffer is 35 mM. In some embodiments, the concentration of acetate buffer is 40 mM. In some embodiments, the concentration of acetate buffer is 45 mM. In some embodiments, the concentration of acetate buffer is 50 mM. In some embodiments, the concentration of acetate buffer is 55 mM. In some embodiments, the concentration of acetate buffer is 60 mM. In some embodiments, the concentration of acetate buffer is 65 mM. In some embodiments, the concentration of acetate buffer is 70 mM. In some embodiments, the concentration of acetate buffer is 75 mM. In some embodiments, the concentration of acetate buffer is about 80 mM. In some embodiments, the concentration of the acetate buffer is 85 mM. In some embodiments, the concentration of the acetate buffer is 90 mM. In some embodiments, the concentration of the acetate buffer is 95 mM. In some embodiments, the concentration of the acetate buffer is 100 mM.

[0039] In some embodiments, the concentration of glutamate buffer is 5 mM. In some embodiments, the concentration of glutamate buffer is 10 mM. In some embodiments, the concentration of glutamate buffer is 15 mM. In some embodiments, the concentration of glutamate buffer is 20 mM. In some embodiments, the concentration of glutamate buffer is 25 mM. In some embodiments, the concentration of glutamate buffer is 30 mM. In some embodiments, the concentration of glutamate buffer is 35 mM. In some embodiments, the concentration of glutamate buffer is 40 mM. In some embodiments, the concentration of glutamate buffer is 45 mM. In some embodiments, the concentration of glutamate buffer is 50 mM. In some embodiments, the concentration of glutamate buffer is 55 mM. In some embodiments, the concentration of glutamate buffer is 60 mM. In some embodiments, the concentration of glutamate buffer is 65 mM. In some embodiments, the concentration of glutamate buffer is 70 mM. In some embodiments, the concentration of glutamate buffer is 75 mM. In some embodiments, the concentration of the glutamate buffer is about 80 mM. In some embodiments, the concentration of the glutamate buffer is 85 mM. In some embodiments, the concentration of the glutamate buffer is 90 mM. In some embodiments, the concentration of the glutamate buffer is 95 mM. In some embodiments, the concentration of the glutamate buffer is 100 mM.

[0040] In some implementations, the buffer does not contain succinate.

[0041] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 50 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises HCDR1 of SEQ ID NO: 53, HCDR2 of SEQ ID NO: 54, HCDR3 of SEQ ID NO: 55, LCDR1 of SEQ ID NO: 56, LCDR2 of SEQ ID NO: 57, and LCDR3 of SEQ ID NO: 58.

[0042] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 50 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises the heavy chain variable region of SEQ ID NO: 14 and the light chain variable region of SEQ ID NO: 13.

[0043] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 50 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises a heavy chain comprising SEQ ID NO: 94 and a light chain comprising SEQ ID NO: 93.

[0044] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 50 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises a heavy chain comprising SEQ ID NO: 92 and a light chain comprising SEQ ID NO: 93.

[0045] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 150 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises HCDR1 of SEQ ID NO: 53, HCDR2 of SEQ ID NO: 54, HCDR3 of SEQ ID NO: 55, LCDR1 of SEQ ID NO: 56, LCDR2 of SEQ ID NO: 57, and LCDR3 of SEQ ID NO: 58.

[0046] In some embodiments, the 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.

[0047] In some implementations, the heavy chain variable region contains SEQ ID NO: 14 and the light chain variable region contains SEQ ID NO: 13.

[0048] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 150 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises the heavy chain variable region of SEQ ID NO: 14 and the light chain variable region of SEQ ID NO: 13.

[0049] In some embodiments, the anti-IGF-1R antibody comprises a heavy chain comprising SEQ ID NO: 92 and a light chain comprising SEQ ID NO: 93.

[0050] In some embodiments, the anti-IGF-1R antibody comprises a heavy chain comprising SEQ ID NO: 94 and a light chain comprising SEQ ID NO: 93.

[0051] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 150 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises a heavy chain comprising SEQ ID NO: 92 and a light chain comprising SEQ ID NO: 93.

[0052] In one aspect, the present invention particularly provides a stable formulation comprising: an anti-IGF-1R antibody at a concentration of 150 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises a heavy chain comprising SEQ ID NO: 94 and a light chain comprising SEQ ID NO: 93.

[0053] In some embodiments, after storage at 40°C for at least 4 weeks, less than 5% of the IGF-1R antibody is present in the formulation as an HMW (Hypothetical Memory Meaning) substance. In some embodiments, after storage at 40°C for at least 4 weeks, less than 4% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 40°C for at least 4 weeks, less than 3% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 40°C for at least 4 weeks, less than 2.5% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 40°C for at least 4 weeks, less than 2% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 40°C for at least 4 weeks, less than 1.5% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 40°C for at least 4 weeks, less than 1% of the IGF-1R antibody is present in the formulation as an HMW substance.

[0054] In some embodiments, after storage at 40°C for at least 4 weeks, at least 90% of the IGF-1R antibody is present in the formulation as a monomer. In some embodiments, after storage at 40°C for at least 4 weeks, at least 92% of the IGF-1R antibody is present in the formulation as a monomer. In some embodiments, after storage at 40°C for at least 4 weeks, at least 93% of the IGF-1R antibody is present in the formulation as a monomer. In some embodiments, after storage at 40°C for at least 4 weeks, at least 94% of the IGF-1R antibody is present in the formulation as a monomer. In some embodiments, after storage at 40°C for at least 4 weeks, at least 95% of the IGF-1R antibody is present in the formulation as a monomer. In some embodiments, after storage at 40°C for at least 4 weeks, at least 96% of the IGF-1R antibody is present in the formulation as a monomer. In some embodiments, after storage at 40°C for at least 4 weeks, at least 97% of the IGF-1R antibody is present in the formulation as a monomer. In some embodiments, after storage at 40°C for at least 4 weeks, at least 98% of the IGF-1R antibody remains in monomeric form in the formulation. In some embodiments, after storage at 40°C for at least 4 weeks, at least 99% of the IGF-1R antibody remains in monomeric form in the formulation.

[0055] In some embodiments, after storage at 5°C for at least 9 months, less than 10% of the IGF-1R antibody is present in the formulation as an HMW (Hypothetical Memory Meaning) substance. In some embodiments, after storage at 5°C for at least 9 months, less than 8% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 7% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 6% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 5% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 4% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 3% of the IGF-1R antibody is present in the formulation as an HMW substance.

[0056] In some embodiments, after storage at 25°C for at least 6 months, less than 1% of the IGF-1R antibody is present in the form of HMW (Hydrogen-Mild Immune Complex). In some embodiments, after storage at 25°C for at least 6 months, less than 2% of the IGF-1R antibody is present in the form of HMW. In some embodiments, after storage at 25°C for at least 6 months, less than 3% of the IGF-1R antibody is present in the form of HMW. In some embodiments, after storage at 25°C for at least 6 months, less than 4% of the IGF-1R antibody is present in the form of HMW. In some embodiments, after storage at 25°C for at least 6 months, less than 5% of the IGF-1R antibody is present in the form of HMW.

[0057] In some implementations, HMW substances or monomers are measured by size exclusion chromatography (SEC).

[0058] In some embodiments, the initial denaturation temperature is above 50°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 55°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 58°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 59°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 60°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 61°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 62°C, as measured by DSC.

[0059] In some embodiments, the acid peak increases by less than 40% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 38% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 36% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 35% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 32% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 30% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 25% after storage at 40°C for at least four weeks, as measured by iCIEF.

[0060] In some embodiments, the clarity of the composition is 20 NTU or less. In some embodiments, the clarity of the composition is 18 NTU or less. In some embodiments, the clarity of the composition is 15 NTU or less. In some embodiments, the clarity of the composition is 13 NTU or less. In some embodiments, the clarity of the composition is 12 NTU or less. In some embodiments, the clarity of the composition is 10 NTU or less. In some embodiments, the clarity of the composition is 8 NTU or less.

[0061] In some embodiments, the formulation is particle-free after storage at 40°C for at least two weeks. In some embodiments, the formulation is particle-free after storage at 40°C for at least three weeks. In some embodiments, the formulation is particle-free after storage at 40°C for at least four weeks. In some embodiments, the formulation is particle-free after storage at 40°C for at least six weeks. In some embodiments, the formulation is particle-free after storage at 40°C for at least two months. In some embodiments, the formulation is particle-free after storage at 40°C for at least four months. In some embodiments, the formulation is particle-free after storage at 40°C for at least six months.

[0062] In some embodiments, the formulation is particle-free after being stored at 25°C for at least two weeks. In some embodiments, the formulation is particle-free after being stored at 25°C for at least three weeks. In some embodiments, the formulation is particle-free after being stored at 25°C for at least four weeks. In some embodiments, the formulation is particle-free after being stored at 25°C for at least six weeks. In some embodiments, the formulation is particle-free after being stored at 25°C for at least two months. In some embodiments, the formulation is particle-free after being stored at 25°C for at least four months. In some embodiments, the formulation is particle-free after being stored at 25°C for at least six months.

[0063] In some embodiments, the purity decreases by less than 8% after storage at 40°C for at least four weeks. In some embodiments, the purity decreases by less than 5% after storage at 40°C for at least four weeks. In some embodiments, the purity decreases by less than 4% after storage at 40°C for at least four weeks. In some embodiments, the purity decreases by less than 3.5% after storage at 40°C for at least four weeks. In some embodiments, the purity decreases by less than 3% after storage at 40°C for at least four weeks. In some embodiments, the purity decreases by less than 2% after storage at 40°C for at least four weeks. In some embodiments, the purity decreases by less than 1% after storage at 40°C for at least four weeks.

[0064] In some implementations, the weight osmotic concentration is between 280 and 380 mOsmol / kg or between 340 and 420 mOsmol / kg.

[0065] In some implementations, the formulation is stored at -25 to 25°C.

[0066] In some implementations, the formulation is stored at 2-8°C.

[0067] In some embodiments, the formulation is suitable for intravenous administration. In some embodiments, the formulation is suitable for subcutaneous administration. In some embodiments, the formulation is suitable for intramuscular administration.

[0068] In some embodiments, the formulation is a liquid pharmaceutical composition. In some embodiments, the formulation is a lyophilized pharmaceutical composition.

[0069] In one aspect, the present invention particularly provides dosage forms comprising the stable formulation of the present invention in vials. In another aspect, the present invention particularly provides dosage forms comprising the stable formulation of the present invention in pre-filled syringes. In yet another aspect, the present invention particularly provides dosage forms comprising the stable formulation of the present invention in autoinjectors.

[0070] In one aspect, the present invention particularly provides the use of a stable formulation for treating thyroid-associated ophthalmopathy in a subject.

[0071] In some implementations, the stabilizing agent is administered intravenously.

[0072] In some implementation methods, the stabilizing agent is administered subcutaneously.

[0073] In one aspect, the present invention particularly provides the use of a stabilizing agent for reducing the clinical activity score (CAS) of thyroid-associated ophthalmopathy (TAO) in a subject, including administration of the stabilizing agent.

[0074] In some implementation schemes, treated subjects experienced a reduction in diplopia.

[0075] In one aspect, the present invention particularly provides the use of a stabilizing agent for treating or reducing the severity of thyroid-associated ophthalmopathy (TAO) in a subject, comprising administering the stabilizing agent wherein treatment with the pharmaceutical composition reduces bulging of the eye by at least 2 mm in one eye; does not result in a deterioration of 2 mm or greater in the other eye (or contralateral eye); and reduces the subject's CAS to one (1) or zero (0).

[0076] In one aspect, the present invention particularly provides the use of a stable formulation for improving the quality of life of subjects suffering from thyroid-associated ophthalmopathy (TAO, also known as Graves' ophthalmopathy / Graves' orbital lesion), including administration of the stable formulation of the present invention.

[0077] In some implementations, quality of life is measured using the Graves' Eye Disease Quality of Life (GO-QoL) assessment. In other implementations, quality of life is measured using a subscale of visual function or appearance.

[0078] In some implementations, the treatment induces improvements in the functional subscales of GO-QoL.

[0079] In some implementations, the treatment induces an improvement in the appearance subscale of GO-QoL.

[0080] In one aspect, the present invention particularly provides the use of a stabilizing agent for treating diplopia or reducing the severity of thyroid-associated ophthalmopathy (TAO) in subjects, including the administration of the stabilizing agent of the present invention.

[0081] In some implementation schemes, diplopia is continuous diplopia.

[0082] In some implementation schemes, diplopia is non-continuous diplopia.

[0083] In some implementation schemes, diplopia is intermittent diplopia.

[0084] In some embodiments, the formulation comprises an anti-IGF-1R antibody or its antigen-binding fragment at a concentration of 25-75 mg / ml and a pH of 4.5-6.0. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment comprises the heavy chain HCDR1 comprising SEQ ID NO: 53, the HCDR2 comprising SEQ ID NO: 54, the HCDR3 comprising SEQ ID NO: 55, the light chain LCDR1 comprising SEQ ID NO: 56, the LCDR2 comprising SEQ ID NO: 57, and the LCDR3 comprising SEQ ID NO: 58.

[0085] In some embodiments, the formulation comprises: (i) an anti-IGF-1R antibody at a concentration of 45-55 mg / ml, wherein the antibody comprises a heavy chain HCDR1 comprising SEQ ID NO: 53, an HCDR2 comprising SEQ ID NO: 54, an HCDR3 comprising SEQ ID NO: 55, a light chain comprising SEQ ID NO: 56, an LCDR2 comprising SEQ ID NO: 57, and an LCDR3 comprising SEQ ID NO: 58; (ii) a buffer at a concentration of about 10-60 mM; (iii) sucrose at a concentration of about 1-20% (w / v); (iv) a stabilizer at a concentration of about 1-15 mM; and (v) a surfactant at a concentration of about 0.001-1% (w / v), and wherein the pharmaceutical composition has a pH of 4.5-6.0.

[0086] In some embodiments, the pH is 5-6. In some embodiments, the pH is 5.5. In some embodiments, the pH is 4.5. In some embodiments, the pH is 6.0. In some embodiments, the pH is about 5 to about 6. In some embodiments, the pH is about 5.5. In some embodiments, the pH is about 4.5. In some embodiments, the pH is about 6.0.

[0087] In some embodiments, the formulation comprises: an anti-IGF-1R antibody at a concentration of 45-55 mg / ml; a histidine buffer at a 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 a pH of 5.5; wherein the antibody comprises the heavy chain HCDR1 of SEQ ID NO: 53, the HCDR2 of SEQ ID NO: 54, the HCDR3 of SEQ ID NO: 55, the light chain LCDR1 of SEQ ID NO: 56, the LCDR2 of SEQ ID NO: 57, and the LCDR3 of SEQ ID NO: 58.

[0088] In some embodiments, the anti-IGF-1R antibody comprises a heavy chain variable region comprising at least 90% (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) of the amino acid sequence identical to SEQ ID NO: 14, and a light chain variable region comprising at least 90% (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) of the amino acid sequence identical to SEQ ID NO: 13, provided that the heavy chain HCDR1 comprises the amino acid sequence SEQ ID NO: 53, HCDR2 comprises the amino acid sequence SEQ ID NO: 54, HCDR3 comprises the amino acid sequence SEQ ID NO: 55, the LCDR1 light chain comprises the amino acid sequence SEQ ID NO: 56, LCDR2 comprises the amino acid sequence SEQ ID NO: 57, and LCDR3 comprises the amino acid sequence SEQ ID NO: 58.

[0089] In some embodiments, the anti-IGF-1R antibody comprises a heavy chain variable region comprising SEQ ID NO: 14 and a light chain variable region comprising SEQ ID NO: 13.

[0090] In some embodiments, the anti-IGF-1R antibody comprises a heavy chain comprising SEQ ID NO: 92 and a light chain comprising SEQ ID NO: 93.

[0091] In some embodiments, the anti-IGF-1R antibody is present at a concentration of 50 mg / ml. In some embodiments, the formulation further comprises sucrose. In some embodiments, sucrose is present at a concentration of about 1-20% (w / v). In some embodiments, sucrose is present at a concentration of about 8% (w / v).

[0092] In some embodiments, the formulation further comprises a stabilizer. In some embodiments, the stabilizer is methionine. Methionine is present at a concentration of about 1-15 mM. In some embodiments, methionine is present at a concentration of about 10 mM.

[0093] In some embodiments, the formulation further comprises a surfactant. In some embodiments, the surfactant is polysorbate 80. In some embodiments, polysorbate 80 is present at a concentration of about 0.001-1% (w / v). In some embodiments, polysorbate 80 is present at a concentration of about 0.02%.

[0094] In some embodiments, the formulation further comprises a buffer. In some embodiments, the buffer is a histidine buffer. In some embodiments, the concentration of the histidine buffer is between about 10-60 mM. In some embodiments, the concentration of the histidine buffer is about 20 mM.

[0095] In some embodiments, the anti-IGF-1R antibody in the formulation is present in the formulation as one or more variants of the anti-IGF-1R antibody. In some embodiments, the anti-IGF-1R antibody variant is described as a monomeric substance, a high molecular weight substance (HMWS), or a charge variant. In some embodiments, the amount of the anti-IGF-1R antibody monomer is (i) 95% or more, as measured by size exclusion chromatography (SEC), and (ii) the amount of the high molecular weight substance (HMWS) is 5% or less, as measured by SEC.

[0096] In some implementations, the formulation comprises an acidic peak, a main peak, and a basic peak, as measured by imaging capillary isoelectric focusing (iCIEF).

[0097] In some embodiments, the formulation is characterized by a charge variant spectrum as measured by iCIEF, which contains (i) 25% or more of the main peak substance, (ii) 70% or less of the acidic substance and (iii) 15% or less of the basic substance.

[0098] In some implementations, after storage at 40°C for 4 weeks relative to the initial value, the percentage increase in the area of ​​the acidic peak in the stable formulation, as measured by iCIEF, is less than 40% (e.g., less than 38%, 36%, 34%, 32%, or 30%).

[0099] In some embodiments, after 4 weeks at 40°C, the percentage reduction in the area of ​​the main peak of the pharmaceutical composition, as measured by iCIEF, relative to the initial value is less than 35% (e.g., less than 34%, less than 33%, less than 32%, less than 31%, less than 30%, less than 29%, less than 28%, less than 27%, less than 26%, less than 25%, less than 24%, less than 23%, less than 22%, less than 21%, or less than 20%).

[0100] In some implementations, after 4 weeks at 40°C, the percentage reduction in the area of ​​the formulation's basic peak, as measured by iCIEF, is less than 6.5% (e.g., less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%) relative to the initial value.

[0101] In some embodiments, the clarity of the stabilized formulation composition is 18 NTU or less. In some embodiments, the weight osmotic concentration of the stabilized formulation is between 280-380 mOsmol / kg or between 340-420 mOsmol / kg. In some embodiments, the weight osmotic concentration of the stabilized formulation is between 280-380 mOsmol / kg. In some embodiments, the weight osmotic concentration of the stabilized formulation is between 340-420 mOsmol / kg.

[0102] In some embodiments, the formulation is stored at -25°C to 25°C. In some embodiments, the stable formulation is stored at 2-8°C. In some embodiments, the formulation is stored at 2-6°C. In some embodiments, the formulation is stored at 4-6°C.

[0103] In some embodiments, the formulation is suitable for intravenous, subcutaneous, or intramuscular administration. In some embodiments, the stabilized formulation is a liquid pharmaceutical composition or a lyophilized pharmaceutical composition. Dosage forms of the stabilized formulation in vials, pre-filled syringes, or autoinjectors are further disclosed herein.

[0104] In some embodiments, a pharmaceutical composition comprising the formulation provided herein is provided. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof; (ii) a buffer solution at a concentration of about 10-60 mM; (iii) sucrose at a concentration of about 1-20% (w / v); (iv) a stabilizer at a concentration of about 1-15 mM; and (v) a surfactant at a concentration of about 0.001-1% (w / v).

[0105] In some embodiments, the antibody or its antigen-binding fragment comprises: a VL sequence as described in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 79 or 86; a VH sequence as described in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 80 or 83; an LCDR sequence as described in SEQ ID NO: 17, 18, 19, 23, 24, 25, 29, 30, 31, 35, 36, 37, 41, 42, 43, 47, 48, 49, 53, 54, 55, 59, 60, 61 or 81; or a sequence as described in SEQ ID NO: The HCDR sequences described in 20, 21, 22, 26, 27, 28, 32, 33, 34, 38, 39, 40, 44, 45, 46, 50, 51, 52, 56, 57, 58, 62, 63 or 64; and any combination or variant thereof.

[0106] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 20; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 21; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 22; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 17; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 18; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 19; or a variant thereof. In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 26; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 27; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 28; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 23; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 24; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 25; or a variant thereof. In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 32; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 33; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 34; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 29; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 30; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 31; or a variant thereof.In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 38; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 39; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 40; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 35; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 36; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 37; or a variant thereof. In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 44; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 45; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 46; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 41; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 42; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 43; or a variant thereof. In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 50; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 51; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 52; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 47; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 48; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 49; or a variant thereof.In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has an amino acid sequence SEQ ID NO: 56; the heavy chain CDR2 sequence has an amino acid sequence SEQ ID NO: 57; and the heavy chain CDR3 sequence has an amino acid sequence SEQ ID NO: 58; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has an amino acid sequence SEQ ID NO: 53; the light chain CDR2 sequence has an amino acid sequence SEQ ID NO: 54; and the light chain CDR3 sequence has an amino acid sequence SEQ ID NO: 55; or a variant thereof. In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 62; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 63; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 64; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 59; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 60; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 61; or a variant thereof. In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has an amino acid sequence SEQ ID NO:38; the heavy chain CDR2 sequence has an amino acid sequence SEQ ID NO:39; and the heavy chain CDR3 sequence has an amino acid sequence SEQ ID NO:40; or a variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has an amino acid sequence SEQ ID NO:35; the light chain CDR2 sequence has an amino acid sequence SEQ ID NO:36; and the light chain CDR3 sequence has an amino acid sequence SEQ ID NO:81; or a variant thereof.

[0107] In some embodiments, the antibody comprises a VL sequence or a variant thereof as described in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 79 or 86.

[0108] In some embodiments, the antibody comprises a VH sequence or a variant thereof as described in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 80 or 83.

[0109] In some embodiments, the antibody comprises V1 and SEQ ID NO: 2; SEQ ID NO: 3 and SEQ ID NO: 4; SEQ ID NO: 5 and SEQ ID NO: 6; SEQ ID NO: 7 and SEQ ID NO: 8; SEQ ID NO: 9 and SEQ ID NO: 10; SEQ ID NO: 11 and SEQ ID NO: 12; SEQ ID NO: 3 and SEQ ID NO: 83; SEQ ID NO: 13 and SEQ ID NO: 14; SEQ ID NO: 15 and SEQ ID NO: 16; SEQ ID NO: 79 and SEQ ID NO: 80; SEQ ID NO: 86 and SEQ ID NO: 14; SEQ ID NO: 98 and SEQ ID NO: 99, respectively. L and V H Or its variants, wherein the CDR of the variants is constant.

[0110] In some implementations, the antibody comprises V of SEQ ID NO: 13 and SEQ ID NO: 14. L and V H Or its variants, wherein the CDR of the variants is constant.

[0111] In some embodiments, the antibody comprises a light chain containing the amino acid sequence SEQ ID NO: 93 and a heavy chain containing the amino acid sequence ID NO: 92; or a light chain containing the amino acid sequence SEQ ID NO: 93 and a heavy chain containing the amino acid sequence ID NO: 94.

[0112] In some implementations, the antibody comprises: V of SEQ ID NO: 98 and SEQ ID NO: 99 L and V H Or a variant thereof (where the CDR of the variant is constant); or a light chain containing the amino acid sequence SEQ ID NO: 3 and a heavy chain containing the amino acid sequence ID NO: 83.

[0113] In some implementations, the variants are associated with V of SEQ ID NO: 1 and SEQ ID NO: 2; SEQ ID NO: 3 and SEQ ID NO: 4; SEQ ID NO: 5 and SEQ ID NO: 6; SEQ ID NO: 7 and SEQ ID NO: 8; SEQ ID NO: 9 and SEQ ID NO: 10; SEQ ID NO: 11 and SEQ ID NO: 12; SEQ ID NO: 3 and SEQ ID NO: 83; SEQ ID NO: 13 and SEQ ID NO: 14; SEQ ID NO: 15 and SEQ ID NO: 16; SEQ ID NO: 79 and SEQ ID NO: 80; SEQ ID NO: 86 and SEQ ID NO: 14; SEQ ID NO: 98 and SEQ ID NO: 99, respectively. L and V H Or its variants have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, wherein the CDR of the variants is constant.

[0114] In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 1-300 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 1-200 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 20-150 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 25 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 50 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 150 mg / mL.

[0115] In some embodiments, the buffer is histidine buffer, histidine HCl buffer, glycine buffer, Tris / glycine buffer, acetate buffer, sodium acetate buffer, potassium acetate buffer, magnesium acetate buffer, phosphate buffer, citrate buffer, or succinate buffer. In some embodiments, the buffer is histidine buffer. In some embodiments, the concentration of the histidine buffer is about 10-60 mM. In some embodiments, the concentration of the histidine buffer is about 10-40 mM. In some embodiments, the concentration of the histidine buffer is about 15-30 mM. In some embodiments, the concentration of the histidine buffer is about 20 mM.

[0116] In some embodiments, the concentration of sucrose is about 1-15% (w / v). In some embodiments, the concentration of sucrose is about 5-10% (w / v). In some embodiments, the concentration of sucrose is about 8% (w / v).

[0117] In some embodiments, the stabilizer or antioxidant is methionine, L-methionine, arginine, glycine, histidine, or proline. In some embodiments, the stabilizer or antioxidant is methionine or L-methionine. In some embodiments, methionine or L-methionine is present at a concentration of about 1-15 mM. In some embodiments, methionine or L-methionine is present at a concentration of about 7-13 mM. In some embodiments, methionine or L-methionine is present at a concentration of about 10 mM.

[0118] In some embodiments, the surfactant is polysorbate or poloxamer. In some embodiments, the polysorbate is polysorbate 80 (PS80) or polysorbate 20 (PS20). In some embodiments, the polysorbate is polysorbate 80 (PS80) or polysorbate 20 (PS20). In some embodiments, the polysorbate is polysorbate 80 (PS80). In some embodiments, polysorbate 80 is present at a concentration of about 0.001-1% (w / v). In some embodiments, polysorbate 80 is present at a concentration of about 0.01-0.1% (w / v). In some embodiments, polysorbate 80 is present at a concentration of about 0.01-0.05% (w / v). In some embodiments, polysorbate 80 is present at a concentration of about 0.01% (w / v). In some embodiments, polysorbate 80 is present at a concentration of about 0.02% (w / v).

[0119] In some embodiments, the pH of the pharmaceutical composition is from about 4.5 to about 6.0. In some embodiments, the pH of the pharmaceutical composition is from about 5.0 to about 6.0. In some embodiments, the pH of the pharmaceutical composition is about 5.5. In some embodiments, the pH of the pharmaceutical composition is about 6.0.

[0120] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of about 10-300 mg / mL; (ii) a histidine buffer at a concentration of about 10-60 mM; (iii) sucrose at a concentration of about 1-20% (w / v); (iv) methionine or L-methionine at a concentration of about 1-15 mM; and (v) polysorbate at a concentration of about 0.001-1% (w / v).

[0121] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof, comprising a light chain comprising the amino acid sequence SEQ ID NO: 1 and a heavy chain comprising the amino acid sequence SEQ ID NO: 2; a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain comprising the amino acid sequence SEQ ID NO: 4; a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain comprising the amino acid sequence SEQ ID NO: 6; a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain comprising the amino acid sequence SEQ ID NO: 8; a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain comprising the amino acid sequence SEQ ID NO: 10; a light chain comprising the amino acid sequence SEQ ID NO: 11 and a heavy chain comprising the amino acid sequence SEQ ID NO: 12; a light chain comprising the amino acid sequence SEQ ID NO: 93 and a heavy chain comprising the amino acid sequence SEQ ID NO: 92; a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain comprising the amino acid sequence SEQ ID NO: 16 ... The pharmaceutical composition comprises: (i) a light chain containing the amino acid sequence SEQ ID NO: 79 and a heavy chain containing the amino acid sequence SEQ ID NO: 80; (ii) a light chain containing the amino acid sequence SEQ ID NO: 3 and a heavy chain containing the amino acid sequence SEQ ID NO: 83; (iii) a light chain containing the amino acid sequence SEQ ID NO: 100 and a heavy chain containing the amino acid sequence SEQ ID NO: 101; or variants thereof, at a concentration of about 10-200 mg / mL; (ii) a histidine buffer at a concentration of about 10-40 mM; (iii) sucrose at a concentration of about 1-10% (w / v); (iv) methionine or L-methionine at a concentration of about 1-15 mM; and (v) polysorbate at a concentration of about 0.01-0.1% (w / v), wherein the pH of the pharmaceutical composition is about 5.0 to about 6.5.

[0122] In some embodiments, the variant antibody has at least 85% homology to the sequence SEQ ID NO: 1-72, 78-83, or 85-86. In some embodiments, the variant has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homology to the sequence SEQ ID NO: 1-72, 78-83, or 85-86. In some embodiments, the variant has at least 85% identity to the sequence SEQ ID NO: 1-72, 78-83, or 85-86. In some embodiments, the variant has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the sequence SEQ ID NO: 1-72, 78-83, or 85-86. In some embodiments, the variant has a constant CDR compared to a reference sequence.

[0123] In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 20-150 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 25 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 50 mg / mL. In some embodiments, the antibody or its antigen-binding fragment is present at a concentration of about 150 mg / mL.

[0124] In some embodiments, the concentration of the histidine buffer is about 15-30 mM. In some embodiments, the concentration of the histidine buffer is about 20 mM.

[0125] In some embodiments, the concentration of sucrose is about 5-10% (w / v). In some embodiments, the concentration of sucrose is about 8% (w / v).

[0126] In some embodiments, methionine or L-methionine is present at a concentration of about 1-15 mM. In some embodiments, methionine or L-methionine is present at a concentration of about 7-13 mM. In some embodiments, methionine or L-methionine is present at a concentration of about 10 mM.

[0127] In some embodiments, the polysorbate is polysorbate 80 (PS80) or polysorbate 20 (PS20). In some embodiments, the polysorbate is polysorbate 80 (PS80). In some embodiments, polysorbate 80 is present at a concentration of about 0.01-0.05% (w / v). In some embodiments, polysorbate 80 is present at a concentration of about 0.01% (w / v). In some embodiments, polysorbate 80 is present at a concentration of about 0.02% (w / v).

[0128] In some embodiments, the pH of the pharmaceutical composition is from about 5.5 to about 6.0. In some embodiments, the pH of the pharmaceutical composition is about 5.5. In some embodiments, the pH of the pharmaceutical composition is about 6.0.

[0129] In some embodiments, the pharmaceutical composition is suitable for intravenous, subcutaneous, or intramuscular administration.

[0130] In some embodiments, the pharmaceutical composition is a liquid pharmaceutical composition.

[0131] In some embodiments, the pharmaceutical composition is a lyophilized pharmaceutical composition.

[0132] In some embodiments, after 4 weeks at 40°C, the percentage area of ​​the main peak of the pharmaceutical composition, as measured by SEC-UPLC, decreases by less than 3% relative to the initial value. In some embodiments, after 4 weeks at 40°C, the percentage area of ​​the main peak of the pharmaceutical composition, as measured by SEC-UPLC, decreases by less than 2% relative to the initial value. In some embodiments, after 4 weeks at 40°C, the percentage area of ​​the main peak of the pharmaceutical composition, as measured by SEC-UPLC, decreases by less than 1.3% relative to the initial value.

[0133] In some embodiments, the dosage form includes a pharmaceutical composition in a container. In some embodiments, the container is a plastic vial or glass vial. In some embodiments, the container is a glass vial with a volume of 2 mL, 6 mL, or 10 mL. In some embodiments, the container is a pre-filled syringe. In some embodiments, the container is an auto-injector.

[0134] In some implementations, the medicine box includes a pharmaceutical composition or dosage form and instructions for use.

[0135] In some embodiments, a method of treating a subject's thyroid-related ophthalmopathy includes administering a pharmaceutical composition to the subject. In some embodiments, the pharmaceutical composition is administered intravenously. In some embodiments, the pharmaceutical composition is administered subcutaneously.

[0136] This document further discloses methods for treating thyroid-associated ophthalmopathy (TAO) or its symptoms or reducing its severity. In some embodiments, treating TAO or its symptoms or reducing its severity includes administering a pharmaceutical composition to a subject. In some embodiments, reducing bulging of the eye in a TAO subject includes administering a pharmaceutical composition to the subject. In some embodiments, treating thyroid ophthalmopathy in a subject includes administering a pharmaceutical composition to the subject. In some embodiments, reducing the CAS of a subject's TAO includes administering a pharmaceutical composition to the subject. In some embodiments, a) reducing bulging by at least 2 mm and b) reducing the CAS of a TAO subject includes administering a pharmaceutical composition to the subject. In some embodiments, bulging is reduced by at least 2 mm. In some embodiments, bulging is reduced by at least 3 mm. In some embodiments, bulging is reduced by at least 4 mm. In some embodiments, the subject's CAS is reduced by at least 2 points. In some embodiments, the subject's CAS is reduced to one (1). In some embodiments, the subject's CAS is reduced to zero (0).

[0137] In some embodiments, treating a subject with TAO or reducing its severity includes administering a pharmaceutical composition to the subject, wherein the use of the pharmaceutical composition to treat (i) reduces the bulging eye in one eye by at least 2 mm; (ii) does not have a deterioration of 2 mm or greater in the other eye (or the contralateral eye); and (iii) reduces the subject's CAS to one (1) or zero (0).

[0138] In some embodiments, improving the quality of life of subjects with thyroid-associated ophthalmopathy (TAO, also known as Graves' ophthalmopathy / Graves' orbital lesion) involves administering a pharmaceutical composition to the subject. In some embodiments, quality of life is measured using the Graves' ophthalmopathy quality of life (GO-QoL) assessment or visual function or its appearance subscale. In some embodiments, treatment results in a GO-QoL improvement of 8 points or more. In some embodiments, treatment results in improvement in the functional subscale of the GO-QoL. In some embodiments, treatment results in improvement in the appearance subscale of the GO-QoL.

[0139] In some embodiments, treating diplopia in a TAO subject or reducing its severity includes administering a pharmaceutical composition to the subject. In some embodiments, the diplopia is continuous. In some embodiments, the diplopia is non-continuous. In some embodiments, the diplopia is intermittent. Detailed Implementation

[0140] This article provides formulations and pharmaceutical compositions of antibodies that bind to and modulate the activity of IGF-1R. The antibodies can be used, for example, to treat thyroid eye diseases (e.g., but not limited to, thyroid-associated ophthalmopathy (TAO)). The formulations and compositions provided herein demonstrate the unexpected stability of the antibodies provided herein (e.g., stabilization at high concentrations of antibody).

[0141] As used herein, the term "pharmaceutical composition" refers to a medical or pharmaceutical preparation containing an active ingredient and one or more excipients and / or diluents to facilitate the use of the active ingredient in a method of administration. The pharmaceutical compositions of this invention comprise pharmaceutically acceptable components compatible with anti-IGF-1R antibodies. As used herein, the terms "pharmaceutical composition" and "stabilized formulation" are used interchangeably.

[0142] In some embodiments, the anti-IGF-1R antibody is VRDN-2700, VRDN-03100, VRDN-02100, VRDN-02200, VRDN-02300, VRDN-02400, VRDN-02500, VRDN-01100, VRDN-02600, or VRDN-02301, the sequences of which are provided herein. In some embodiments, more than one anti-IGF-1R antibody is present. In some embodiments, the anti-IGF-1R antibody is a biosimilar of any of the anti-IGF-1R antibodies provided herein. In some embodiments, the Fc domain of the antibody is not fucosylated. In some embodiments, the Fc domain of the antibody is not glycosylated. As provided herein, in some embodiments, the Fc domain contains a mutation compared to the wild type.

[0143] As used herein, the term "pharmaceuticalally acceptable carrier" refers to an excipient or diluent in a pharmaceutical composition. A pharmaceutically acceptable carrier must be compatible with the other components of the formulation and be harmless to the recipient. The nature of the carrier varies depending on the mode of administration. For example, aqueous carriers are typically used for intravenous administration, while solid carriers are typically used for oral administration.

[0144] TAO is the most common autoimmune disorder associated with Graves' disease and hyperthyroidism, but it can also occur in patients with normal or hypothyroidism. Orbital lesions in TAO are caused by thyroid-stimulating hormone receptor (TSHR) agonist autoantibodies and crosstalk between TSHR and IGF-1R. Pathological remodeling of the orbit and surrounding tissues leads to various presentations, including dry eye, increased tearing, local irritation, eyelid retraction and eventual ptosis, diplopia and optic nerve compression, and subsequent visual loss. People with TAO may also be said to have thyroid ophthalmopathy (TED).

[0145] The underlying pathology of TAO is the activation of an intraorbital inflammatory cascade, primarily driven by the recruitment of fibroblasts and immune cells. IGF-1R overexpression has been confirmed in the orbit of TAO patients, and it is hypothesized that IGF-1R inhibitory antibodies can disrupt IGF-1R and TSHR crosstalk and suppress the inflammatory cascade. Indeed, IGF-1R antagonism has been shown to robustly alleviate many inflammatory symptoms affecting TAO patients.

[0146] As used in this article, "thyroid-associated ophthalmopathy" (TAO), "thyroid eye disease" (TED), "Graves' ophthalmopathy," or "Graves' orbital lesion" (GO) refer to the same condition or disorder and are used interchangeably. All of them refer to inflammatory orbital symptoms associated with some autoimmune thyroid disorders, most commonly Graves' disease (GD), but sometimes associated with other diseases (e.g., Hashimoto's thyroiditis).

[0147] The terms “protruding eye” and “eyeball protrusion” (also known as ptosis, exophthalmos, or bulging eye) refer to the forward protrusion, displacement, bulging, or projection of an organ. As used herein, the term refers to the forward protrusion, displacement, bulging, or projection of the eye from the orbit. Those skilled in the art will consider protruding eye and eyeball protrusion to have the same meaning and to be used interchangeably, while others will consider minor differences in their meaning. Some those skilled in the art use eyeball protrusion to refer to severe protruding eye; or to endocrine-related protruding eye. However, others use the term eyeball protrusion when describing eye-related protruding eye in subjects, for example, those with TAO (TED or GO).

[0148] As used herein, the terms “protruding eye” and “bulging eyeball” are used interchangeably and refer to the forward projection, displacement, bulging, or protrusion of the eye from the orbit. Because the rigid bony structure of the orbit is used only for expansion at its anterior opening, any increase in the soft tissue contents of the orbit occurring from the side or back will cause forward displacement of the eyeball. Protruding eye or bulging eyeball can result from several disease processes, including infection, inflammation, tumors, trauma, metastasis, endocrine lesions, vascular diseases, and extraorbital lesions. TAO (TED or GO) is currently considered the most common cause of protruding eye in adults. Protrusion can be bilateral (as is frequently seen in TAO (TED or GO)) or unilateral (as is frequently seen in orbital tumors). Based on currently available or future available technologies, those skilled in the art will be able to determine the best approach for diagnosing and assessing the degree of protruding eye or bulging eyeball.

[0149] As used herein, the term "antibody" refers to any form of antibody that exhibits the desired biological activity. Therefore, it is used in the broadest sense and specifically encompasses (but is not limited to) monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized full-length human antibodies, chimeric antibodies, and camelified single-domain antibodies. A "parental antibody" is an antibody obtained by preserving the immune system in the antigen prior to improving the antibody for its intended use (e.g., humanized antibodies used as human therapeutic antibodies).

[0150] The “Fc” region contains two C-cell antibodies. H 1 and C H 2. Heavy chain segments of the structural domain. Two heavy chain segments are connected by two or more disulfide bonds and by C... H The hydrophobic interactions of the three domains remain together.

[0151] In some embodiments, the antibody comprises an Fc domain. In some embodiments, the Fc domain contains a mutation to extend the antibody's half-life. In some embodiments, the Fc domain contains a mutation (e.g., those set forth in U.S. Patent No. 7,670,600, which is incorporated herein by reference in its entirety). In some embodiments, the constant region contains a mutation at amino acid residue position 428 (according to Kabat's EU number index) relative to the constant domain of wild-type human IgG. Without being limited to any particular theory, an antibody containing a mutation corresponding to residue 428 may have an increased half-life compared to IgG having the constant domain of wild-type human IgG. In some embodiments, the mutation is the substitution of a natural residue with threonine, leucine, phenylalanine, or serine. In some embodiments, the antibody further comprises one or more amino acid substitutions relative to the corresponding wild-type human IgG constant domain at one or more of amino acid residues 251-256, 285-290, 308-314, 385-389, and 429-436, as indexed according to the Kabat EU numbering. Specific mutations or substitutions at these locations are described in U.S. Patent No. 7,670,600 (incorporated herein by reference in its entirety).

[0152] In some embodiments, the Fc region contains S228P, L235E, M252Y, S254T, T256E, M428L, N434S, L234F, P331S mutations or any combination thereof. In some embodiments, the Fc region contains M252Y, S254T, and T256E mutations. Non-limiting examples of Fc regions containing M252Y, S254T, and T256E mutations (collectively, “YTE mutations”) can be found in sequence SEQ ID NO: 89. In some embodiments, the Fc region containing the YTE mutation is contained in sequence SEQ ID NO: 90, which differs from SEQ ID NO: 89 in the presence of a C-terminal lysine (K) residue. The Fc region may be numbered according to the Kabat numbering system for Fc regions.

[0153] In some embodiments, the Fc region contains S228P and L235E mutations. In some embodiments, the antibody contains L234F, L235E, and P331S mutations. In some embodiments, the Fc region contains M252Y, S254T, T256E, S228P, and L235E mutations. In some embodiments, the Fc region contains S228P, L235E, M428L, and N434S mutations. In some embodiments, the Fc region contains M428L and N434S mutations. In some embodiments, the Fc region contains L234F, L235E, P331S, M252Y, S254T, and T256E mutations. Mutations in the Fc region are also described in US2007041972A1, EP2235059B1, US Patent No. 8,394,925, and Mueller et al., Mol Immunol, April 1997;34(6):441-52, each of which is incorporated herein by reference in its entirety. References herein refer to the Kabat numbering system for the Fc region.

[0154] In some implementations, the Fc region contains sequences selected from the following: APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO: 75); APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 76); or APPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQID NO: 77); or ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 84) ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 87) ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 88) ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 89) ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 90) In some embodiments, the anti-IGF-1R antibody is a variant antibody. Typically, the variant antibody or antigen-binding fragment of the antibody provided herein retains at least 10% of its IGF-1R binding activity, expressed in molar quantities, when compared to the modified parent antibody. In some embodiments, the variant antibody (or its antigen fragment) or antigen-binding fragment of the antibody provided herein retains at least 20%, 50%, 70%, 80%, 90%, 95%, or 100% or more of the IGF-1R binding affinity of the parent antibody. As illustrated herein, it is also intended that the antibody or its antigen-binding fragment may contain conserved or non-conserved amino acid substitutions that do not substantially alter its biological activity; these may also be referred to as “conserved variants” or “functionally conserved variants” of the antibody.

[0155] As used herein, the term "monoclonal antibody" refers to a group of substantially homologous antibodies, meaning that antibody molecules comprising this group have the same amino acid sequence except for trace amounts of possible natural mutations. The modifier "monoclonal" indicates that the antibody is derived from a substantially homologous group of antibodies and should not be construed as requiring any specific method to produce the antibody. For example, the monoclonal antibodies to be used as presented herein can be derived from those produced by Kohler et al. (1975). Nature The monoclonal antibody can be prepared using the hybridoma method described in 256:495, or by a recombinant DNA method (see, for example, U.S. Patent No. 4,816,567). The “monoclonal antibody” can also be isolated from an autophagy antibody library using the techniques described below: for example, Clackson et al. (1991). Nature 352: 624-628 and Marks et al. (1991) J. Mol. Biol 222: 581-597. See also Presta (2005). J. Allergy Clin. Immunol 116:731.

[0156] Generally, the basic antibody structural unit comprises a tetramer. Each tetramer contains two pairs of identical polypeptide chains, each pair having a "light" chain (approximately 25 kDa) and a "heavy" chain (approximately 50-70 kDa). The amino-terminal portion of each chain contains a variable region of approximately 100 to 110 or more amino acids primarily responsible for antigen recognition. The carboxyl-terminal portion of the heavy chain defines a constant region primarily responsible for effector function. Human light chains are typically classified as κ and λ light chains. Furthermore, human heavy chains are generally classified as μ, δ, γ, α, or ε, and antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE, respectively. Within both the light and heavy chains, the variable and constant regions are linked by a "J" region of approximately 12 or more amino acids, with the heavy chain also containing a "D" region of approximately 10 or more amino acids. See also [link to relevant documentation]. Fundamental Immunology Chapter 7 (edited by Paul, W., 2nd edition, Raven Press, NY (1989)).

[0157] Each light / heavy chain pair has a variable region that forms an antibody binding site. Therefore, generally, a complete antibody has two binding sites. Typically, the variable domains of both the heavy and light chains contain three hypervariable regions, also known as complementarity-determining regions (CDRs), located within relatively conserved frame regions (FRs). The CDRs are usually arranged along the frame regions to enable binding to specific epitopes. Generally, from the N-terminus to the C-terminus, both the light and heavy chain variable domains contain FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. Unless otherwise specified, the amino acid assignment in each domain is generally according to the definitions below: Sequences of Proteins of Immunological InterestKabat et al.; National Institutes of Health, Bethesda, Md.; 5th edition; NIH Publication No. 91-3242 (1991); Kabat (1978) Adv. Prot. Chem. 32:1-75; Kabat et al., (1977) J. Biol. Chem. 252:6609-6616; Chothia et al., (1987) J Mol. Biol. 196:901-917 or Chothia et al., (1989) Nature 342:878-883.

[0158] As used in this article, the term "hypervariant region" refers to the antibody amino acid residues responsible for antigen binding. The hypervariable region contains amino acid residues from the complementarity-determining region (CDRL) or CDR (i.e., residues 24-34 (CDRL1), 50-56 (CDRL2), and 89-97 (CDRL3) in the light chain variable domain and residues 31-35 (CDRH1), 50-65 (CDRH2), and 95-102 (CDRH3) in the heavy chain variable domain; Kabat et al., (1991) Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, Md.) and / or residues from the hypervariable ring (i.e., residues 26-32 (CDRL1), 50-52 (CDRL2), and 91-96 (CDRL3) in the light chain variable domain and residues 26-32 (CDRH1), 53-55 (CDRH2), and 96-101 (CDRH3) in the heavy chain variable domain). (Chothia and Lesk (1987)) J. Mol. Biol (196: 901-917). As used herein, the term "frame" or "FR" residue refers to variable domain residues that are different from the hypervariable region residues defined herein as CDR residues. CDRs provide most of the contact residues for antibody binding to antigens or epitopes. CDRs of interest may be derived from the variable heavy and light chain sequences of donor antibodies and include analogs of native CDRs that also share or retain the same antigen-binding specificity and / or neutralizing capacity with the donor antibody from which they are derived.

[0159] The term "homology" refers to a protein sequence that has 40% to 100% sequence homology or identity with a reference sequence. The percentage of identity between two peptide chains can be determined by contrastive alignment using the default settings of the AlignX module in Vector NTI v.9.0.0 (Invitrogen Corp., Carslbad, Calif.). In some embodiments, the antibody or its antigen-binding fragment has at least 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% homology or identity with the sequence described herein. In some embodiments, the antibody has conserved substitutions compared to the sequence described herein. Exemplary conserved substitutions are illustrated in Table 1 and are covered within the scope of the disclosed subject matter. Conservative substitutions may be present in the frame region or antigen-binding site, provided they do not adversely affect the properties of the antibody. Substitutions may be made to improve antibody properties (e.g., stability or affinity). Conservative substitutions will produce molecules with similar functional and chemical properties to those molecules that have undergone such modifications. Examples of amino acid substitutions are shown in Table 1 below.

[0160] In some embodiments, variants of the proteins and peptides provided herein are provided. In some embodiments, the variants contain substitutions, deletions, or insertions. In some embodiments, the variants contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1-10) substitutions. As described herein, substitutions may be conserved. In some embodiments, substitutions are non-conserved. In some embodiments, the variants contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1-10) deletions. In some embodiments, the variants contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1-10) insertions. In some embodiments, substitutions, deletions, or insertions are present in the CDR provided herein. In some embodiments, substitutions, deletions, or insertions are not present in the CDR provided herein. In some embodiments, the variant antibody has a constant or unchanged CDR compared to the reference sequence. In other words, the light chain or heavy chain may vary compared to the reference sequence within the light chain and heavy chain framework regions, but the CDR remains unchanged.

[0161] As described herein, the production of antibodies with known sequences is conventional and can be accomplished by any method. Therefore, in some embodiments, a nucleic acid encoding an antibody or a fragment thereof is provided. In some embodiments, the nucleic acid encodes the sequence provided herein. Antibodies can also be used in injectable pharmaceutical compositions. Also as described herein, antibodies can be isolated antibodies or engineered antibodies.

[0162] The nucleic acid sequence encoding the antibody described herein may be genomic DNA, cDNA, or RNA (e.g., mRNA) encoding at least one of the variable regions described herein. A convenient alternative to using chromosomal gene fragments as the DNA source encoding the V region antigen-binding segment is to construct chimeric immunoglobulin genes using cDNA, as reported, for example, by Liu et al. (Proc. Natl. Acad. Sci., USA 84:3439 (1987) and J. Immunology 139:3521 (1987), the entire references of which are hereby incorporated by reference. Using cDNA requires combining gene expression elements suitable for the host cell with the gene to achieve the synthesis of the desired protein. The advantage of using cDNA sequences compared to genomic sequences (which contain introns) is that cDNA sequences can be expressed in bacteria or other hosts lacking a suitable RNA splicing system.

[0163] For example, cDNA encoding a V region antigen-binding segment capable of detecting, binding, or neutralizing IGF-1R antigens can be provided using known methods based on the amino acid sequences provided herein. Because the genetic code is degenerate, more than one codon can be used to encode a specific amino acid (Watson et al., infra). The genetic code can be used to identify one or more distinct oligonucleotides, each capable of encoding an amino acid. The probability that a particular oligonucleotide actually constitutes the actual XXX coding sequence can be estimated by considering anomalous base pairings and the frequency with which a particular codon (encoding a specific amino acid) is actually used in eukaryotic or prokaryotic cells expressing antibodies or fragments. Such "codon usage rules" are disclosed by Lathe et al., J. Molec. Biol. 183:112 (1985). Lathe's "codon usage rules" are used to identify a single oligonucleotide or a group of oligonucleotides containing the theoretically "most likely" nucleotide sequence capable of encoding the variable or constant region sequence of an antibody.

[0164] As used herein and unless otherwise indicated, the term “about” is intended to mean ± 5% of its modified value. Thus, about 100 means 95 to 105.

[0165] The term "purified" for antibodies refers to antibodies that are substantially free of other material that binds to molecules in their natural environment. For example, a purified protein is one that is substantially free of cellular material or other proteins derived from its cells or tissues. The term also refers to formulations in which the isolated protein is sufficiently pure for analysis, or at least 70% to 80% (w / w) pure, at least 80%-90% (w / w) pure, 90-95% pure; and at least 95%, 96%, 97%, 98%, 99%, or 100% (w / w) pure. In some embodiments, the antibody is purified.

[0166] As used herein, the term "stable" or its grammatical equivalent refers to the ability of an antibody to maintain all or most of its intended biological activity and / or physiological and chemical integrity over time. Generally, the antibodies described herein are formulated such that the formulation stabilizes the antibody formulated with it, or alternatively slows or prevents its degradation. In the context of formulations, a stable formulation is one in which the antibody retains its basic physical and / or chemical integrity after storage and during processes such as (but not limited to) storage at specific temperatures, freezing / thawing, thermal stress (e.g., at about 40°C or higher), mechanical mixing, or lyophilization. A "stable" formulation containing an anti-IGF-1R antibody retains some or all of its biological activity against the IGF-1R protein and for the treatment of TAO.

[0167] In some embodiments, antibody stability in the formulation can be measured by the formation of high molecular weight (HMW) aggregates, loss of activity, formation of peptide fragments, and shifts in the charge spectrum. In some embodiments, shifts in the charge spectrum can be measured by iCIEF as the relative percentage of the main peak, acidic peak, and / or basic peak. For example, a stable formulation may be one in which, after storage at 40°C for four weeks, the change in the acidic peak relative to the initial value increases by less than 40% (e.g., less than 38%, 36%, 34%, 32%, 30%, 28%, 26%, 24%, 22%, or less than 20%), as measured by iCIEF and quantified using chromatographic software. In some embodiments, a stable formulation is one in which the percentage of the main peak decreases by less than 35% relative to the initial value after four weeks of storage at 40°C (e.g., less than 34%, less than 33%, less than 32%, less than 31%, less than 30%, less than 29%, less than 28%, less than 27%, less than 26%, less than 25%, less than 24%, less than 23%, less than 22%, less than 21%, or less than 20%), as measured by iCIEF and quantified using chromatographic software. In some embodiments, after four weeks at 40°C, the percentage of the area of ​​the basic peak in the stable formulation, as measured by iCIEF, decreases by less than 6.5% relative to the initial value (e.g., less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%).

[0168] In some embodiments, the stabilizing formulation is characterized by the amount of high molecular weight (HMW) aggregates. In some embodiments, the amount of high molecular weight substance (HMWS) in the stabilizing formulation is less than 10% (e.g., less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%), as measured by SEC. In some embodiments, the amount of high molecular weight substance (HMWS) in the stabilizing formulation is less than 5%, as measured by SEC. In some embodiments, the stability based on HMW or HMWS is based on the composition stored at 40°C for a period of time (e.g., 4 weeks).

[0169] Any numerical values ​​used in this application mean any variation or normal fluctuation within the standard deviation that would be understood by a person of ordinary skill in the art.

[0170] Anti-IGF-1R antibody This document provides non-limiting examples of anti-IGF-1R antibodies. In some embodiments, the antibody is a recombinant antibody that binds to the IGF-1R protein. In some embodiments, the IGF-1R protein is the human IGF-1R protein. In some embodiments, the IGF-1R protein recognized by the antibody is in its native (non-denatured) conformation. In some embodiments, the antibody does not specifically bind to denatured IGF-1R protein. As used herein, the term "recombinant antibody" refers to a non-natural antibody. In some embodiments, the term "recombinant antibody" refers to an antibody that was not isolated from a human subject.

[0171] In some implementations, the antibody comprises one or more peptides having the sequences listed in Table 2 below or variants thereof.

[0172] Table 2. IGF-1R light and heavy chain sequences

[0173] In some implementations, the antibody comprises one or more peptides having the sequences listed in Table 3 below or variants thereof.

[0174] Table 3. Variable light chain and variable heavy chain sequences of IGF-1R antibody

[0175] The column indicating the antibody sequence contains the VH and VL chains of the antibody. In some cases where the VH chain is elucidated using the Fc sequence, the Fc sequence may be modified or substituted with different Fc regions as provided herein. However, in some embodiments, the antibody may contain the VH and VL sequences as provided in the tables provided herein.

[0176] In some embodiments, such as the variable light chain described in SEQ ID NO: 13, the chain does not have a C-terminal arginine residue. This is illustrated, for example, in the following sequence: DVVMTQTPLSLPVSLGDPASISCRSSQSIVHSNVNTYLEWYLQKPGQSPRLLIYKVSNRFSGVPDRFSGSGAGTDFTLRISRVEAEDLGIYYCFQGSHVPPTFGGGTKLEIK (SEQ ID NO: 97).

[0177] Therefore, in some implementations, if the variable light chain contains sequence SEQ ID NO: 13, it may be replaced by sequence SEQ ID NO: 97.

[0178] In some embodiments, such as the heavy chain variable region described in SEQ ID NO: 14, the heavy chain may contain C22S substitution. This is illustrated in the following sequence: QVQLVQSGAEVVKPGASVKLSSKASGYTFTSYWMHWVKQRPGQGLEWIGEINPSNGRTNYNQKFQGKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGRPDYYGSSKWYFDVWGQGTTVTVSS (SEQ ID NO: 96).

[0179] Therefore, in some embodiments, the antibody comprises the VH sequence SEQ ID NO: 96 and the VL sequence SEQ ID NO: 13 or SEQ ID NO: 97.

[0180] In one embodiment, the antibody comprises VH SEQ ID NO: 14 and VL SEQ ID NO: 97.

[0181] In some embodiments, the antibody comprises VL SEQ ID NO: 98 and VH SEQ ID NO: 99. In some embodiments, the antibody comprises VL SEQ ID NO: 98 and VH SEQ ID NO: 99, wherein the Fc region contains M252Y, S254T, and T256E mutations. In some embodiments, the antibody comprises VL SEQ ID NO: 98 and VH SEQ ID NO: 99, wherein the Fc region contains M428L and N434S mutations.

[0182] As presented in this article, the heavy chain can be linked to the Fc region (including those Fc regions with mutations that can affect the antibody's half-life). This article provides information on non-restrictive mutations in the Fc region.

[0183] In the tables provided herein, LC and HC can be interpreted using VH and VL domains with or without constant regions. Constant regions can be substituted as provided herein. VH and VL regions can be used to form antibodies as provided herein.

[0184] In some implementations, an antibody or its antigen-binding fragment is provided, wherein the antibody or antibody fragment contains a CDR selected from Tables 4-7 below.

[0185] Table 4. IGF-1R antibody Kabat CDR

[0186] Table 5. IGF-1R antibody IMGT CDR

[0187] Table 6. IGF-1R antibody CDR in Chothia

[0188] Table 7. IGF-1R antibody North CDR

[0189] In some embodiments, the antibody or antibody-binding fragment thereof comprises a heavy chain or light chain CDR having sequences SEQ ID NO: 17-64 and 81. In some embodiments, the antibody or antibody-binding fragment thereof comprises a light chain CDR having sequences SEQ ID NO: 17, 18, 19, 23, 24, 25, 29, 30, 31, 35, 36, 37, 41, 42, 43, 47, 48, 49, 53, 54, 55, 59, 60, 61, or 81. In some embodiments, the antibody or antibody-binding fragment thereof comprises a heavy chain CDR having sequences SEQ ID NO: 20, 21, 22, 26, 27, 28, 32, 33, 34, 38, 39, 40, 44, 45, 46, 50, 51, 52, 56, 57, 58, 62, 63, or 64.

[0190] In some embodiments, the antibody or its antibody-binding fragment comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 17, 23, 29, 35, 41, 47, 53, or 59, LCDR2 has the sequence SEQ ID NO: 18, 24, 30, 36, 42, 48, 54, or 60, and LCDR3 has the sequence SEQ ID NO: 19, 25, 31, 37, 43, 49, 55, 61, or 81.

[0191] In some embodiments, the antibody or its antibody-binding fragment comprises a heavy chain having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 20, 26, 32, 38, 44, 50, 56 or 62, HCDR2 has the sequence SEQ ID NO: 21, 27, 33, 39, 45, 51, 57 or 63 and HCDR3 has the sequence SEQ ID NO: 22, 28, 34, 40, 46, 52, 58 or 64.

[0192] Different CDR motifs can be combined in any combination, including those not described in the table above. For example, the following embodiments are provided as a non-limiting example of such combinations.

[0193] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 17; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 18; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 20; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 21; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 22; or a variant of any of the above.

[0194] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 23; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 24; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 25; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 26; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 27; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 28; or a variant of any of the above.

[0195] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 29; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 30; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 31; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 32; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 33; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 34; or a variant of any of the above.

[0196] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 35; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 36; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 37; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 38; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 39; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 40; or a variant of any of the above.

[0197] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 41; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 42; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 43; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 44; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 45; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 46; or a variant of any of the above.

[0198] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 47; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 48; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 49; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 50; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 51; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 52; or a variant of any of the above.

[0199] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 53; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 54; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 55; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 56; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 57; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 58; or a variant of any of the above.

[0200] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 59; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 60; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 61; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 62; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 63; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 64; or a variant of any of the above.

[0201] In some embodiments, the antibody or its antigen-binding fragment comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence SEQ ID NO: 35; the light chain CDR2 sequence has the amino acid sequence SEQ ID NO: 36; and the light chain CDR3 sequence has the amino acid sequence SEQ ID NO: 81; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 38; the heavy chain CDR2 sequence has the amino acid sequence SEQ ID NO: 39; and the heavy chain CDR3 sequence has the amino acid sequence SEQ ID NO: 40; or a variant of any of the above.

[0202] In some embodiments, the antibody or its antibody-binding fragment comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 102, LCDR2 has the sequence SEQ ID NO: 103, and LCDR3 has the sequence SEQ ID NO: 55. In some embodiments, the antibody or its antibody-binding fragment comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 104, HCDR2 has the sequence SEQ ID NO: 105, and HCDR3 has the sequence SEQ ID NO: 106. In some embodiments, the antibody or its antibody-binding fragment comprises: (i) a light chain having LCDR1, LCDR2 and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 102, LCDR2 has the sequence SEQ ID NO: 103 and LCDR3 has the sequence SEQ ID NO: 55, and (ii) a heavy chain having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 104, HCDR2 has the sequence SEQ ID NO: 105 and LCDR3 has the sequence SEQ ID NO: 106.

[0203] In some embodiments, the antibody or its antibody-binding fragment comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 53, LCDR2 has the sequence SEQ ID NO: 54, and LCDR3 has the sequence SEQ ID NO: 55. In some embodiments, the antibody or its antibody-binding fragment comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 111, HCDR2 has the sequence SEQ ID NO: 112, and HCDR3 has the sequence SEQ ID NO: 58. In some embodiments, the antibody or its antibody-binding fragment comprises: (i) a light chain having LCDR1, LCDR2 and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 53, LCDR2 has the sequence SEQ ID NO: 54 and LCDR3 has the sequence SEQ ID NO: 55, and (ii) a heavy chain having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 111, HCDR2 has the sequence SEQ ID NO: 112 and HCDR3 has the sequence SEQ ID NO: 58.

[0204] In some embodiments, the antibody or its antibody-binding fragment comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 53, LCDR2 has the sequence SEQ ID NO: 113, and LCDR3 has the sequence SEQ ID NO: 55. In some embodiments, the antibody or its antibody-binding fragment comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 114, HCDR2 has the sequence SEQ ID NO: 115, and HCDR3 has the sequence SEQ ID NO: 106. In some embodiments, the antibody or its antibody-binding fragment comprises: (i) a light chain having LCDR1, LCDR2 and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 53, LCDR2 has the sequence SEQ ID NO: 113 and LCDR3 has the sequence SEQ ID NO: 55, and (ii) a heavy chain having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 114, HCDR2 has the sequence SEQ ID NO: 115 and HCDR3 has the sequence SEQ ID NO: 106.

[0205] In some embodiments, the antibody or its antibody-binding fragment comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 107, LCDR2 has the sequence SEQ ID NO: 103, and LCDR3 has the sequence SEQ ID NO: 25. In some embodiments, the antibody or its antibody-binding fragment comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 108, HCDR2 has the sequence SEQ ID NO: 109, and HCDR3 has the sequence SEQ ID NO: 110. In some embodiments, the antibody or its antibody-binding fragment comprises: (i) a light chain having LCDR1, LCDR2 and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 107, LCDR2 has the sequence SEQ ID NO: 103 and LCDR3 has the sequence SEQ ID NO: 25, and (ii) a heavy chain having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 108, HCDR2 has the sequence SEQ ID NO: 109 and HCDR3 has the sequence SEQ ID NO: 110.

[0206] In some embodiments, the antibody or its antibody-binding fragment comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 23, LCDR2 has the sequence SEQ ID NO: 24, and LCDR3 has the sequence SEQ ID NO: 25. In some embodiments, the antibody or its antibody-binding fragment comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 108, HCDR2 has the sequence SEQ ID NO: 112, and HCDR3 has the sequence SEQ ID NO: 28. In some embodiments, the antibody or its antibody-binding fragment comprises: (i) a light chain having LCDR1, LCDR2 and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 23, LCDR2 has the sequence SEQ ID NO: 24 and LCDR3 has the sequence SEQ ID NO: 25, and (ii) a heavy chain having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 108, HCDR2 has the sequence SEQ ID NO: 112 and LCDR3 has the sequence SEQ ID NO: 28.

[0207] In some embodiments, the antibody or its antibody-binding fragment comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 23, LCDR2 has the sequence SEQ ID NO: 118, and LCDR3 has the sequence SEQ ID NO: 25. In some embodiments, the antibody or its antibody-binding fragment comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 116, HCDR2 has the sequence SEQ ID NO: 117, and LCDR3 has the sequence SEQ ID NO: 110. In some embodiments, the antibody or its antibody-binding fragment comprises: (i) a light chain having LCDR1, LCDR2 and LCDR3, wherein LCDR1 has the sequence SEQ ID NO: 25, LCDR2 has the sequence SEQ ID NO: 118 and LCDR3 has the sequence SEQ ID NO: 25, and (ii) a heavy chain having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence SEQ ID NO: 116, HCDR2 has the sequence SEQ ID NO: 117 and LCDR3 has the sequence SEQ ID NO: 110.

[0208] In some embodiments, the light chain variable region CDR1 is replaced by any of the other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced by any of the other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced by any of the other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced by any of the other light chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced by any of the other light chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced by any of the other light chain CDR3 sequences.

[0209] In some embodiments, an antibody or its antigen-binding fragment or protein is provided, comprising a peptide having a sequence as described in any of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 79 or 86 and 2, 4, 6, 8, 10, 12, 14, 16, 80 or 83.

[0210] In some implementations, the antibody or its antigen-binding fragment contains a sequence or variant of any of the above.

[0211] In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 65 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 66 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 67 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 68 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 69 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 70 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 71 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 72 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 78 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment comprises sequence SEQ ID NO: 82 or a variant of any of the above. In some embodiments, the antibody or its antigen-binding fragment contains the sequence SEQ ID NO: 85 or a variant of any of the above.

[0212] In some implementation schemes, V L and / or VH The sequence is as provided herein. In some implementations, V L The sequence is provided as an element of the light chain (LC). In some embodiments, V is provided as an element of the light chain (LC). L The sequence is underlined in the LC sequence. In some implementations, V is provided as an element of the heavy chain (HC). H The sequence is underlined in the HC sequence.

[0213] In some embodiments, the antibody or its antigen-binding fragment comprises V as described in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 79 or 86 or any combination thereof. L Peptide. V L Peptides may contain variants of any of these sequences as provided herein.

[0214] In some embodiments, the antibody or its antigen-binding fragment comprises V as described in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 80 or 83 or any combination thereof. H Peptide. V H Peptides may contain variants of any of these sequences as provided herein.

[0215] In some embodiments, the antibody or its antigen-binding fragment contains V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 80 or 83 and V L The peptide comprises the sequence described in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 79 or 86.

[0216] In some embodiments, the antibody or its antigen-binding fragment contains V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 2 and V L The peptide comprises the sequence as described in SEQ ID NO: 1. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 4 and V L The peptide comprises the sequence as described in SEQ ID NO: 3. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which VH The peptide comprises the sequence as described in SEQ ID NO: 6 and V L The peptide comprises the sequence as described in SEQ ID NO: 5. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 8 and V L The peptide comprises the sequence as described in SEQ ID NO: 7. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 10 and V L The peptide comprises the sequence as described in SEQ ID NO: 9. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 12 and V L The peptide comprises the sequence described in SEQ ID NO: 11. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 14 and V L The peptide comprises the sequence described in SEQ ID NO: 13. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 16 and V L The peptide comprises the sequence described in SEQ ID NO: 15. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 80 and V L The peptide comprises the sequence described in SEQ ID NO: 79. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 83 and V LThe peptide comprises the sequence as described in SEQ ID NO: 3. In some embodiments, the antibody or its antigen-binding fragment comprises V H Peptides and Vitamins L peptides, of which V H The peptide comprises the sequence as described in SEQ ID NO: 14 and V L The peptide comprises the sequence described in SEQ ID NO: 86.

[0217] In some embodiments, the antibody or its antigen-binding fragment comprises an LC peptide as described in SEQ ID NO: 1, 3, 5, 7, 9, or 11, or any combination thereof. The LC peptide may comprise a variant of any of these sequences provided herein.

[0218] In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide as described in SEQ ID NO: 2, 4, 6, 8, 10, 12, or 83, or any combination thereof. The HC peptide may comprise a variant of any of these sequences provided herein.

[0219] In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 2, 4, 6, 8, 10, 12, or 83 and the LC peptide comprises the sequence described in SEQ ID NO: 1, 3, 5, 7, 9, or 11. In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 2 and the LC peptide comprises the sequence described in SEQ ID NO: 1. In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 4 and the LC peptide comprises the sequence described in SEQ ID NO: 3. In some embodiments, the HC peptide comprising the sequence described in SEQ ID NO: 4 has an additional C-terminal lysine (K) residue. In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 6 and the LC peptide comprises the sequence described in SEQ ID NO: 5. In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 8 and the LC peptide comprises the sequence described in SEQ ID NO: 7. In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 10 and the LC peptide comprises the sequence described in SEQ ID NO: 9. In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 12 and the LC peptide comprises the sequence described in SEQ ID NO: 11. In some embodiments, the antibody or its antigen-binding fragment comprises an HC peptide and an LC peptide, wherein the HC peptide comprises the sequence described in SEQ ID NO: 83 and the LC peptide comprises the sequence described in SEQ ID NO: 3.

[0220] In addition to these specific combinations, V H Peptides and Vitamins L Any of the peptides can combine with each other.

[0221] In addition to these specific combinations, either HC peptide or LC peptide can be combined with each other.

[0222] In some embodiments, the antibody comprises a sequence or antigen-binding fragment of the ATCC clone PTA-7444. The antibody sequence derived from the ATCC clone PTA-7444 is incorporated herein by reference in its entirety, including its antigen-binding fragment.

[0223] In some implementations, the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the following sequences: QVQLVQSGAEVVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEINPSNGRTNYNQKFQGKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGRPDYYGSSKWYFDV WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 92); and the light chain contains the following sequence: DVVMTQTPLSLPVSLGDPASISCRSSQSIVHSNVNTYLEWYLQKPGQSPRLLIYKVSNRFSGVPDRFSGSGAGTDFTLRISRVEAEDLGIYYCFQGSHVPPTFGGGTKLEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO: 93).

[0224] In some implementations, the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the following sequences: QVQLVQSGAEVVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEINPSNGRTNYNQKFQGKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGRPDYYGSSKWYFDV WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKS CDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 94); And the light chain contains the following sequence DVVMTQTPLSLPVSLGDPASISCRSSQSIVHSNVNTYLEWYLQKPGQSPRLLIYKVSNRFSGVPDRFSGSGAGTDFTLRISRVEAEDLGIYYCFQGSHVPPTFGGGTKLEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO: 93).

[0225] In some embodiments, the heavy chain of SEQ ID NO: 94 contains a C-terminal lysine residue added to the C-terminus of SEQ ID NO: 94.

[0226] In some implementations, the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the following sequences: QVQLVQSGAEVVKPGASVKLSSKASGYTFTSYWMHWVKQRPGQGLEWIGEINPSNGRTNYNQKFQGKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGRPDYYGSSKWYFDV WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKS CDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 95); The light chain contains the sequence SEQ ID NO: 93.

[0227] In some embodiments, the heavy chain of SEQ ID NO: 95 contains a C-terminal lysine residue added to the C-terminus of SEQ ID NO: 95.

[0228] In some embodiments, the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the sequence SEQ ID NO: 83 and the light chain comprises the sequence SEQ ID NO: 3.

[0229] In some embodiments, the antibody comprises the VH sequence SEQ ID NO: 96 and the VL sequence SEQ ID NO: 13 or SEQ ID NO: 97. In some embodiments, the antibody comprises the VH sequence SEQ ID NO: 14 and the VL sequence SEQ ID NO: 97.

[0230] In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 85% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 90% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 91% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 92% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 93% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 94% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 95% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 96% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 97% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 98% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 99% identical to that of SEQ ID NO: 92. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 85% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 90% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 91% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 92% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 93% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 94% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 95% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 96% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 97% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 98% identical to that of SEQ ID NO: 93. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 99% identical to that of SEQ ID NO: 93.

[0231] In some embodiments, the IGF-1R antibody contains at least 85% the same V as SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 90% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 91% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 92% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 93% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 94% identical V sequence to SEQ ID NO:91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 95% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 96% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 97% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 98% identical V sequence to SEQ ID NO: 91. H Sequence. In some embodiments, the IGF-1R antibody contains at least 99% identical V sequence to SEQ ID NO: 91. H sequence.

[0232] In some embodiments, the IGF-1R antibody contains at least 85% of the same V as SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 90% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 91% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 92% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 93% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 94% identical V sequence to SEQ ID NO:86.L Sequence. In some embodiments, the IGF-1R antibody contains at least 95% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 96% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 97% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 98% identical V sequence to SEQ ID NO: 86. L Sequence. In some embodiments, the IGF-1R antibody contains at least 99% identical V sequence to SEQ ID NO: 86. L sequence.

[0233] In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 85% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 90% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 91% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 92% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 93% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 94% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 95% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 96% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 97% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 98% identical to that of SEQ ID NO: 94. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 99% identical to that of SEQ ID NO: 94.

[0234] In some embodiments, the IGF-1R antibody comprises at least 85% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises at least 90% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises at least 91% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises at least 92% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises at least 93% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises at least 94% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises at least 95% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises at least 96% of the heavy chain identical to SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 97% identical to that of SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 98% identical to that of SEQ ID NO: 83. In some embodiments, the IGF-1R antibody comprises a heavy chain that is at least 99% identical to that of SEQ ID NO: 83.

[0235] In some embodiments, the IGF-1R antibody comprises at least 85% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 90% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 91% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 92% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 93% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 94% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 95% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 96% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises at least 97% of a light chain identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 98% identical to that of SEQ ID NO: 3. In some embodiments, the IGF-1R antibody comprises a light chain that is at least 99% identical to that of SEQ ID NO: 3.

[0236] In some implementations, the IGF-1R antibody contains at least 85% the same V as SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 90% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 91% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 92% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 93% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 94% identical V sequence to SEQ ID NO:99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 95% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 96% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 97% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 98% identical V sequence to SEQ ID NO: 99. H Sequence. In some embodiments, the IGF-1R antibody contains at least 99% identical V sequence to SEQ ID NO: 99. H sequence.

[0237] In some embodiments, the IGF-1R antibody contains at least 85% the same V as SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 90% identical V sequence to SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 91% identical V sequence to SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 92% identical V sequence to SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 93% identical V sequence to SEQ ID NO: 98. LSequence. In some embodiments, the IGF-1R antibody contains at least 94% identical V sequence to SEQ ID NO:98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 95% identical V sequence to SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 96% identical V sequence to SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 97% identical V sequence to SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 98% identical V sequence to SEQ ID NO: 98. L Sequence. In some embodiments, the IGF-1R antibody contains at least 99% identical V sequence to SEQ ID NO: 98. L sequence.

[0238] Pharmaceutical Compositions / Stabilizing Formulations This invention relates to anti-IGF-1R antibody compositions or stable formulations containing IGF-1R antibodies. Throughout this specification, the terms "pharmaceutical composition" and "stable formulation" are used interchangeably.

[0239] Throughout this invention, unless otherwise indicated, all expressions of percentages, ratios, etc., are “by weight.” As used herein, “by weight” is synonymous with the term “by mass” and indicates that the ratios or percentages defined herein are based on weight and not on volume, thickness, or some other measure.

[0240] As used herein, the term "anti-IGF-1R antibody composition" refers to a composition comprising one or more anti-IRG-1R antibodies or one or more of their antigen-binding fragments.

[0241] antibody concentration In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition in amounts of 1 mg / ml to 300 mg / ml, 1 mg / ml to 200 mg, 10 mg / ml to 200 mg, 20 mg / ml to 150 mg / ml, 25 mg / ml to 150 mg / ml, 25 mg / ml to 125 mg / ml, 25 mg / ml to 100 mg / ml, 25 mg / ml to 75 mg / ml, 30 mg / ml to 60 mg / ml, or 45 mg / ml to 55 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at amounts of 20 mg / ml, 25 mg / ml, 30 mg / ml, 40 mg / ml, 45 mg / ml, 50 mg / ml, 55 mg / ml, 60 mg / ml, 65 mg / ml, 70 mg / ml, 75 mg / ml, 80 mg / ml, 85 mg / ml, 90 mg / ml, 95 mg / ml, 100 mg / ml, 125 mg / ml, 150 mg / ml, 175 mg / ml, 200 mg / ml, 225 mg / ml, 250 mg / ml, 275 mg / ml, or 300 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at amounts of 25 mg / ml, 50 mg / ml, or 150 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 20 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 25 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 30 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 40 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 45 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 50 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 55 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 60 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 65 mg / ml.In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 70 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 75 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 80 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 85 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 90 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 95 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 100 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 125 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 150 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 175 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 200 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 225 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 250 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 275 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present in the pharmaceutical composition at an amount of 300 mg / ml.

[0242] In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 20 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 25 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 40 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 50 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 75 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 90 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 100 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 120 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 140 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 160 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 180 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration greater than 200 mg / ml.

[0243] In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 1 mg / ml to 300 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 1 mg / ml to 200 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 10 mg / ml to 200 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 20 mg / ml to 150 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 25 mg / ml to 150 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 25 mg / ml to 125 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 25 mg / ml to 100 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 25 mg / ml to 75 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 30 mg / ml to 60 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 45 mg / ml to 55 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 100 mg / ml to 300 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 105 mg / ml to 180 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 120 mg / ml to 160 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 125 mg / ml to 175 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 110 mg / ml to 140 mg / ml. In some embodiments, the anti-IGF-1R antibody or its antigen-binding fragment is present at a concentration of 165 mg / ml to 185 mg / ml.

[0244] buffer solution In some embodiments, the pharmaceutical composition comprises a buffer (e.g., histidine, acetate, phosphate, or citrate buffer) and / or a stabilizer (e.g., human albumin) or a combination thereof. In some embodiments, the pharmaceutical composition comprises one or more pharmaceutically acceptable carriers, including ion exchangers, alumina, aluminum stearate, lecithin, serum proteins (e.g., human serum albumin), buffering substances (e.g., phosphates), sucrose, glycine, sorbic acid, potassium sorbate, a mixture of metaglycerides of saturated vegetable fatty acids, water, salts or electrolytes (e.g., protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate), polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, polyethylene-polyoxypropylene-block copolymers, and polyethylene glycol or combinations thereof.

[0245] Various buffers may be present in the anti-IGF-1R antibody composition of the present invention. In some embodiments, the pharmaceutical composition comprises a pharmaceutically acceptable buffer, wherein the pharmaceutically acceptable buffer is phosphate buffer, citrate buffer, acetate buffer, citrate buffer, ascorbic acid buffer, glutamate buffer, lactate buffer, maleate buffer, glycerol buffer, gluconate buffer, acetate buffer, succinate buffer, phosphate buffer, histidine buffer, or any combination thereof. In some embodiments, the buffer is histidine buffer, histidine HCl buffer, glycine buffer, Tris / glycine buffer, acetate buffer, sodium acetate buffer, potassium acetate buffer, magnesium acetate buffer, phosphate buffer, or citrate buffer. In some embodiments, the buffer is histidine buffer. In some embodiments, the buffer is histidine HCl buffer. In some embodiments, the buffer is glycine buffer. In some embodiments, the buffer is Tris / glycine buffer. In some embodiments, the buffer is acetate buffer. In some embodiments, the buffer is sodium acetate buffer. In some embodiments, the buffer is potassium acetate buffer. In some embodiments, the buffer is magnesium acetate buffer. In some cases, the buffer is phosphate buffer. In some implementations, the buffer is a citrate buffer. In some implementations, the buffer is not a succinate buffer.

[0246] Unless otherwise specified, the buffer solution contains an acid and its conjugate base sufficient to adjust and maintain the pH. Those skilled in the art will be able to determine the acid and its conjugate base used in a particular buffer solution. In some embodiments, the histidine buffer solution contains histidine and histidine hydrochloride. In some embodiments, the histidine buffer solution contains L-histidine and L-histidine-HCl. In some embodiments, the acetate buffer solution (acetic acid buffer) contains acetic acid and sodium acetate. In some embodiments, the glutamate buffer solution contains glutamate and monosodium glutamate.

[0247] In some embodiments, the pharmaceutically acceptable buffer is phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM phosphate buffer to 100 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 25 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 95 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 100 mM phosphate buffer.

[0248] In some embodiments, the pharmaceutically acceptable buffer is citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM citrate buffer to 100 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 25 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM citrate buffer. In some embodiments, a pharmaceutically acceptable buffer is 95 mM citrate buffer. In some embodiments, a pharmaceutically acceptable buffer is 100 mM citrate buffer.

[0249] In some embodiments, the pharmaceutically acceptable buffer is acetate buffer (acetate saline). In some embodiments, the pharmaceutically acceptable buffer is 5 mM acetate buffer to 100 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 25 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 95 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 100 mM acetate buffer.

[0250] In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 100 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 25 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM succinate buffer. In some embodiments, a pharmaceutically acceptable buffer is 95 mM succinate buffer. In some embodiments, a pharmaceutically acceptable buffer is 100 mM succinate buffer.

[0251] In some embodiments, the pharmaceutically acceptable buffer is 5 mM citrate buffer to 100 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 25 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM citrate buffer. In some embodiments, the pharmaceutically acceptable buffer is 95 mM citrate buffer. In some implementations, a pharmaceutically acceptable buffer is a 100 mM citrate buffer.

[0252] In some embodiments, the pharmaceutically acceptable buffer is 5 mM glutamate buffer to 100 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 25 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM glutamate buffer. In some embodiments, the pharmaceutically acceptable buffer is 95 mM glutamate buffer. In some implementations, a pharmaceutically acceptable buffer is a 100 mM glutamate buffer.

[0253] In some embodiments, the pharmaceutically acceptable buffer is 5 mM acetate buffer to 100 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to about 25 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM acetate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 25 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 30 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 35 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 40 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 45 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 50 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 55 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 60 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 75 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 80 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 85 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 90 mM acetate buffer. In some embodiments, a pharmaceutically acceptable buffer is 95 mM acetate buffer. In some implementations, a pharmaceutically acceptable buffer is a 100 mM acetate buffer.

[0254] In some embodiments, the acetate buffer is a potassium acetate buffer, a sodium acetate buffer, or a magnesium acetate buffer. In some embodiments, the acetate buffer is a potassium acetate buffer. In some embodiments, the acetate buffer concentration provided above is provided for potassium acetate buffer. In some embodiments, the acetate buffer is a sodium acetate buffer. In some embodiments, the acetate buffer concentration provided above is provided for sodium acetate buffer. In some embodiments, the acetate buffer is a magnesium acetate buffer. In some embodiments, the acetate buffer concentration provided above is provided for magnesium acetate buffer.

[0255] In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 100 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM succinate buffer. In some embodiments, the buffer is 15 mM to about 25 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM succinate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM succinate buffer. In some embodiments, a pharmaceutically acceptable buffer is a 95 mM succinate buffer. In some embodiments, a pharmaceutically acceptable buffer is a 100 mM succinate buffer.

[0256] In some embodiments, the succinate buffer is a sodium succinate buffer. In some embodiments, the sodium succinate buffer is provided at the succinate buffer concentration provided above.

[0257] In some embodiments, the pharmaceutically acceptable buffer is 5 mM phosphate buffer to 100 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 25 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM phosphate buffer. In some embodiments, the pharmaceutically acceptable buffer is 95 mM phosphate buffer. In some implementations, a pharmaceutically acceptable buffer is 100 mM phosphate buffer.

[0258] In some embodiments, the phosphate buffer is sodium phosphate. In some embodiments, the sodium phosphate buffer is present at the phosphate buffer concentration provided above.

[0259] In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 100 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 70 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 50 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM to 60 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM to 40 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to 30 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM to about 25 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 5 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 10 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 15 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 20 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 25 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 30 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 35 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 40 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 45 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 50 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 55 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 60 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 75 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 80 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 85 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 90 mM histidine buffer. In some embodiments, the pharmaceutically acceptable buffer is 95 mM histidine buffer. In some implementations, a pharmaceutically acceptable buffer is a 100 mM histidine buffer.

[0260] Electroless excipients and sugars In some embodiments, the anti-IGF-1R antibody compositions of the present invention comprise a charge-free excipient. The term "excipient" refers to a pharmacologically inert substance formulated with an antibody or its antigen-binding fragment as described herein. In some embodiments, the charge-free excipient helps prevent denaturation or otherwise helps stabilize the antibody or its antigen-binding fragment. Examples of excipients known in the art are available, for example, from the handbook: Gennaro, Alfonso R.: “Remington's Pharmaceutical Sciences”, Mack Publishing Company, Easton, Pa., 1990.

[0261] In some embodiments, the non-electrostatic excipient is fructose, glucose, mannose, sorbitol, xylose, lactose, maltose, sucrose, dextran, pullulan, dextrin, cyclodextrin, soluble starch, trehalose, sorbitol, erythritol, isomaltitol, lactitol, maltitol, xylitol, glycerol, lactitol, hydroxyethyl starch, water-soluble dextran, or combinations thereof. In some embodiments, the non-electrostatic excipient is sucrose. In some embodiments, the non-electrostatic excipient is trehalose. In some embodiments, the non-electrostatic excipient is mannitol.

[0262] In some embodiments, the uncharged excipient is present in the anti-IGF-1R antibody composition at an amount of 0.5% (w / v) to 20% (w / v) (e.g., 0.5% to 20%, 1% to 20%, 1% to 15%, 1% to 10%, 2% to 10%, 3% to 10%, 4% to 10%, 5% to 10%, 6% to 10%, 7% to 10%, 7.5% to 10%, 7.5% to 8.5%, 7.5% to 8%). In some embodiments, the uncharged excipient is present at a concentration of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 0.5% (w / v) to 20% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 0.5% (w / v) to 20% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 1% (w / v) to 20% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 1% (w / v) to 15% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 1% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 2% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 3% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 4% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 5% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 6% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 7% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 7.5% (w / v) to 10% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 7.5% (w / v) to 8.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 7.5% (w / v) to 8% (w / v).

[0263] In some embodiments, the uncharged excipient is present at a concentration of 0.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 1% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 1.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 2% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 2.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 3% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 3.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 4% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 4.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 5.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 6% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 6.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 7% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 7.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 8% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 8.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 9% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 9.5% (w / v). In some embodiments, the uncharged excipient is present at a concentration of 10% (w / v).

[0264] In some embodiments, sucrose is present in the anti-IGF-1R antibody composition at an amount of 0.5% (w / v) to 20% (w / v) (e.g., 0.5% to 20%, 1% to 20%, 1% to 15%, 1% to 10%, 2% to 10%, 3% to 10%, 4% to 10%, 5% to 10%, 6% to 10%, 7% to 10%, 7.5% to 10%, 7.5% to 8.5%, 7.5% to 8%). In some embodiments, sucrose is present at a concentration of 0.5% (w / v) to 20% (w / v). In some embodiments, sucrose is present at a concentration of 0.5% (w / v) to 20% (w / v). In some embodiments, sucrose is present at a concentration of 1% (w / v) to 20% (w / v). In some embodiments, sucrose is present at a concentration of 1% (w / v) to 15% (w / v). In some embodiments, sucrose is present at a concentration of 1% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 2% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 3% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 4% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 5% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 6% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 7% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 7.5% (w / v) to 10% (w / v). In some embodiments, sucrose is present at a concentration of 7.5% (w / v) to about 8.5% (w / v).

[0265] In some embodiments, sucrose is present at a concentration of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% (w / v). In some embodiments, sucrose is present at a concentration of 0.5% (w / v). In some embodiments, sucrose is present at a concentration of 1% (w / v). In some embodiments, sucrose is present at a concentration of 1.5% (w / v). In some embodiments, sucrose is present at a concentration of 2% (w / v). In some embodiments, sucrose is present at a concentration of 2.5% (w / v). In some embodiments, sucrose is present at a concentration of 3% (w / v). In some embodiments, sucrose is present at a concentration of 3.5% (w / v). In some embodiments, sucrose is present at a concentration of 4% (w / v). In some embodiments, sucrose is present at a concentration of 4.5% (w / v). In some embodiments, sucrose is present at a concentration of 5% (w / v). In some embodiments, sucrose is present at a concentration of 5.5% (w / v). In some embodiments, sucrose is present at a concentration of 6% (w / v). In some embodiments, sucrose is present at a concentration of 6.5% (w / v). In some embodiments, sucrose is present at a concentration of 7% (w / v). In some embodiments, sucrose is present at a concentration of 7.5% (w / v). In some embodiments, sucrose is present at a concentration of 8% (w / v). In some embodiments, sucrose is present at a concentration of 8.5% (w / v). In some embodiments, sucrose is present at a concentration of 9% (w / v). In some embodiments, sucrose is present at a concentration of 9.5% (w / v). In some embodiments, sucrose is present at a concentration of 10% (w / v).

[0266] stabilizer In some embodiments, the pharmaceutical composition comprises a stabilizer. In some embodiments, the stabilizer is an amino acid. In some embodiments, the stabilizer comprises methionine, L-methionine, arginine, L-arginine, glycine, L-glycine, histidine, L-histidine, proline, or L-proline. In some embodiments, the stabilizer is methionine, L-methionine, arginine, L-arginine, glycine, L-glycine, histidine, L-histidine, proline, or L-proline. In some embodiments, the stabilizer is methionine. In some embodiments, the stabilizer is L-methionine. In some embodiments, the stabilizer is arginine. In some embodiments, the stabilizer is L-arginine. In some embodiments, the stabilizer is glycine. In some embodiments, the stabilizer is L-glycine. In some embodiments, the stabilizer is histidine. In some embodiments, the stabilizer is L-histidine. In some embodiments, the stabilizer is proline. In some embodiments, the stabilizer is L-proline.

[0267] In some embodiments, the anti-IGF-1R antibody composition of the present invention comprises methionine.

[0268] Methionine as used herein includes the free base form of methionine and any and all its salts. In some embodiments, methionine includes its pharmaceutically acceptable salts (e.g., methionine hydrochloride). Methionine as used herein also includes all enantiomers (e.g., L-methionine and S-methionine) and any combination of enantiomers (e.g., 50% L-methionine and 50% S-methionine; 90%-100% L-methionine and 10%-0% S-methionine, etc.). In some embodiments, the term "methionine" includes greater than 99% L-methionine and less than 1% S-methionine. In some embodiments, the term "methionine" includes enantiomerically pure L-methionine. In some embodiments, methionine is pharmaceutical grade methionine.

[0269] In some embodiments, the anti-IGF-1R antibody composition of the present invention comprises arginine.

[0270] As used herein, arginine includes the free base form of arginine and any and all its salts. In some embodiments, arginine includes its pharmaceutically acceptable salts (e.g., arginine hydrochloride). As used herein, arginine also includes all enantiomers (e.g., L-arginine and S-arginine) and any combination of enantiomers (e.g., 50% L-arginine and 50% S-arginine; 90%-100% L-arginine and 10%-0% S-arginine, etc.). In some embodiments, the term "arginine" includes greater than 99% L-arginine and less than 1% S-arginine. In some embodiments, the term "arginine" includes enantiomerically pure L-arginine. In some embodiments, arginine is pharmaceutical grade arginine.

[0271] In some embodiments, the anti-IGF-1R antibody composition of the present invention includes glycine.

[0272] As used herein, glycine includes the free base form of arginine and any and all its salts. In some embodiments, arginine includes its pharmaceutically acceptable salts (e.g., glycine hydrochloride). As used herein, glycine also includes all enantiomers (e.g., L-glycine and S-glycine) and any combination of enantiomers (e.g., 50% L-glycine and 50% S-glycine; 90%-100% L-glycine and 10%-0% S-glycine, etc.). In some embodiments, the term "glycine" includes greater than 99% L-glycine and less than 1% S-glycine. In some embodiments, the term "glycine" includes enantiomerically pure L-glycine. In some embodiments, glycine is pharmaceutical grade glycine.

[0273] In some embodiments, the anti-IGF-1R antibody composition of the present invention comprises histidine.

[0274] As used herein, histidine includes the free base form of histidine and any and all its salts. In some embodiments, histidine includes its pharmaceutically acceptable salts (e.g., histidine hydrochloride). As used herein, histidine also includes all enantiomers (e.g., L-histidine and S-histidine) and any combination of enantiomers (e.g., 50% L-histidine and 50% S-histidine; 90%-100% L-histidine and 10%-0% S-histidine, etc.). In some embodiments, the term "histidine" includes greater than 99% L-histidine and less than 1% S-histidine. In some embodiments, the term "histidine" includes enantiomerically pure L-histidine. In some embodiments, histidine is pharmaceutical grade histidine.

[0275] In some embodiments, the anti-IGF-1R antibody composition of the present invention includes proline.

[0276] As used herein, proline includes the free base form of proline and any and all its salts. In some embodiments, proline includes its pharmaceutically acceptable salts (e.g., proline hydrochloride). As used herein, proline also includes all enantiomers (e.g., L-proline and S-proline) and any combination of enantiomers (e.g., 50% L-proline and 50% S-proline; 90%-100% L-proline and 10%-0% S-proline, etc.). In some embodiments, the term "proline" includes greater than 99% L-proline and less than 1% S-proline. In some embodiments, the term "proline" includes enantiomerically pure L-proline. In some embodiments, proline is pharmaceutical grade proline.

[0277] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of stabilizer. In some embodiments, the pharmaceutical composition comprises greater than 1 mM, greater than 2 mM, greater than 3 mM, or greater than 4 mM of stabilizer. In other aspects, the pharmaceutical composition comprises up to 5 mM, up to 6 mM, up to 7 mM, up to 8 mM, up to 9 mM, up to 10 mM, up to 11 mM, up to 12 mM, up to 13 mM, up to 15 mM, up to 20 mM, or up to 200 mM of stabilizer. In some embodiments, the stabilizing agent comprises greater than 1 mM of stabilizer. In some embodiments, the stabilizing agent comprises greater than 2 mM of stabilizer. In some embodiments, the stabilizing agent comprises greater than 3 mM of stabilizer. In some embodiments, the stabilizing agent comprises greater than 4 mM of stabilizer. In other aspects, the stabilizing agent comprises up to 5 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 6 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 7 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 8 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 9 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 10 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 11 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 12 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 13 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 15 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 20 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 0 mM of stabilizer. In some embodiments, the stabilizing agent comprises up to 200 mM of stabilizer.

[0278] In other aspects, the pharmaceutical composition includes a stabilizer of 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 15 mM, 7 mM to 13 mM, 9 mM to 11 mM, or 10 mM. In some embodiments, the pharmaceutical composition includes a 10 mM stabilizer. In some embodiments, the stabilizing agent includes a 1 mM to 200 mM stabilizer. In some embodiments, the stabilizing agent includes a 1 mM to 150 mM stabilizer. In some embodiments, the stabilizing agent includes a 1 mM to 100 mM stabilizer. In some embodiments, the stabilizing agent includes a 1 mM to 50 mM stabilizer. In some embodiments, the stabilizing agent includes a 1 mM to 25 mM stabilizer. In some embodiments, the stabilizing agent includes a 1 mM to 15 mM stabilizer. In some embodiments, the stabilizing agent comprises 7 mM to 13 mM of stabilizer. In some embodiments, the stabilizing agent comprises 9 mM to 11 mM of stabilizer. In some embodiments, the stabilizing agent comprises 5 mM of stabilizer. In some embodiments, the stabilizing agent comprises 10 mM of stabilizer. In some embodiments, the stabilizing agent comprises 15 mM of stabilizer. In some embodiments, the stabilizing agent comprises 20 mM of stabilizer. In some embodiments, the stabilizing agent comprises 25 mM of stabilizer. In some embodiments, the stabilizing agent comprises 30 mM of stabilizer. In some embodiments, the stabilizing agent comprises 35 mM of stabilizer. In some embodiments, the stabilizing agent comprises 40 mM of stabilizer.

[0279] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of methionine. In some embodiments, the pharmaceutical composition comprises greater than 1 mM methionine, greater than 2 mM methionine, greater than 3 mM methionine, or greater than 4 mM methionine. In other aspects, the pharmaceutical composition comprises up to 5 mM methionine, up to 6 mM methionine, up to 7 mM methionine, up to 8 mM methionine, up to 9 mM methionine, up to 10 mM methionine, up to 11 mM methionine, up to 12 mM methionine, up to 13 mM methionine, up to 14 mM methionine, up to 15 mM methionine, or up to 200 mM methionine. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 15 mM, 7 mM to 13 mM, 9 mM to 11 mM, or 10 mM methionine. In some embodiments, the pharmaceutical composition comprises 5 mM methionine. In some embodiments, the pharmaceutical composition comprises 10 mM methionine. In some embodiments, the stabilizing agent comprises greater than 1 mM methionine. In some embodiments, the stabilizing agent comprises greater than 2 mM methionine. In some embodiments, the stabilizing agent comprises greater than 3 mM methionine. In some embodiments, the stabilizing agent comprises greater than 4 mM methionine. In other aspects, the stabilizing agent comprises up to 5 mM methionine. In some embodiments, the stabilizing agent comprises up to 6 mM methionine. In some embodiments, the stabilizing agent comprises up to 7 mM methionine. In some embodiments, the stabilizing agent comprises up to 8 mM methionine. In some embodiments, the stabilizing agent contains up to 9 mM methionine. In some embodiments, the stabilizing agent contains up to 10 mM methionine. In some embodiments, the stabilizing agent contains up to 11 mM methionine. In some embodiments, the stabilizing agent contains up to 12 mM methionine. In some embodiments, the stabilizing agent contains up to 13 mM methionine. In some embodiments, the stabilizing agent contains up to 15 mM methionine. In some embodiments, the stabilizing agent contains up to 15 mM methionine. In some embodiments, the stabilizing agent contains up to 20 mM methionine. In some embodiments, the stabilizing agent contains up to 200 mM methionine. In some embodiments, the stabilizing agent contains 1 mM to 200 mM methionine. In some embodiments, the stabilizing agent contains 1 mM to 150 mM methionine. In some embodiments, the stabilizing agent contains 1 mM to 100 mM methionine. In some embodiments, the stabilizing agent contains 1 mM to 50 mM methionine.In some embodiments, the stabilizing agent comprises 1 mM to 25 mM methionine. In some embodiments, the stabilizing agent comprises 1 mM to 15 mM methionine. In some embodiments, the stabilizing agent comprises 7 mM to 13 mM methionine. In some embodiments, the stabilizing agent comprises 9 mM to 11 mM methionine. In some embodiments, the stabilizing agent comprises 5 mM methionine. In some embodiments, the stabilizing agent comprises 10 mM methionine. In some embodiments, the stabilizing agent comprises 15 mM methionine. In some embodiments, the stabilizing agent comprises 20 mM methionine. In some embodiments, the stabilizing agent comprises 25 mM methionine. In some embodiments, the stabilizing agent comprises 30 mM methionine. In some embodiments, the stabilizing agent comprises 35 mM methionine. In some embodiments, the stabilizing agent comprises 40 mM methionine. In some embodiments, methionine is added in an amount sufficient to maintain the weight osmotic concentration of the pharmaceutical composition. In some embodiments, methionine is added in an amount sufficient to achieve a hypertonic solution.

[0280] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of L-methionine. In some embodiments, the pharmaceutical composition comprises greater than 1 mM L-methionine, greater than 2 mM L-methionine, greater than 3 mM L-methionine, or greater than 4 mM L-methionine. In other aspects, the pharmaceutical composition comprises up to 5 mM L-methionine, up to 6 mM L-methionine, up to 7 mM L-methionine, up to 8 mM L-methionine, up to 9 mM L-methionine, up to 10 mM L-methionine, up to 11 mM L-methionine, up to 12 mM L-methionine, up to 13 mM L-methionine, up to 14 mM L-methionine, up to 15 mM L-methionine, or up to 200 mM L-methionine. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 15 mM, 7 mM to 13 mM, 9 mM to 11 mM, or 10 mM L-methionine. In some embodiments, the pharmaceutical composition comprises 10 mM L-methionine. In some embodiments, the pharmaceutical composition comprises 10 mM L-methionine. In some embodiments, the stabilizing agent comprises more than 1 mM L-methionine. In some embodiments, the stabilizing agent comprises more than 2 mM L-methionine. In some embodiments, the stabilizing agent comprises more than 3 mM L-methionine. In some embodiments, the stabilizing agent comprises more than 4 mM L-methionine. In other aspects, the stabilizing agent comprises up to 5 mM L-methionine. In some embodiments, the stabilizing agent comprises up to 6 mM L-methionine. In some embodiments, the stabilizing agent comprises up to 7 mM L-methionine. In some embodiments, the stabilizing agent contains up to 8 mM L-methionine. In some embodiments, the stabilizing agent contains up to 9 mM L-methionine. In some embodiments, the stabilizing agent contains up to 10 mM L-methionine. In some embodiments, the stabilizing agent contains up to 11 mM L-methionine. In some embodiments, the stabilizing agent contains up to 12 mM L-methionine. In some embodiments, the stabilizing agent contains up to 13 mM L-methionine. In some embodiments, the stabilizing agent contains up to 15 mM L-methionine. In some embodiments, the stabilizing agent contains up to 15 mM L-methionine. In some embodiments, the stabilizing agent contains up to 20 mM L-methionine. In some embodiments, the stabilizing agent contains up to 200 mM L-methionine. In some embodiments, the stabilizing agent contains 1 mM to 200 mM L-methionine.In some embodiments, the stabilizing agent comprises 1 mM to 150 mM L-methionine. In some embodiments, the stabilizing agent comprises 1 mM to 100 mM L-methionine. In some embodiments, the stabilizing agent comprises 1 mM to 50 mM L-methionine. In some embodiments, the stabilizing agent comprises 1 mM to 25 mM L-methionine. In some embodiments, the stabilizing agent comprises 1 mM to 15 mM L-methionine. In some embodiments, the stabilizing agent comprises 7 mM to 13 mM L-methionine. In some embodiments, the stabilizing agent comprises 9 mM to 11 mM L-methionine. In some embodiments, the stabilizing agent comprises 5 mM L-methionine. In some embodiments, the stabilizing agent comprises 10 mM L-methionine. In some embodiments, the stabilizing agent comprises 15 mM L-methionine. In some embodiments, the stabilizing agent comprises 20 mM L-methionine. In some embodiments, the stabilizing agent comprises 25 mM L-methionine. In some embodiments, the stabilizing agent comprises 30 mM L-methionine. In some embodiments, the stabilizing agent comprises 35 mM L-methionine. In some embodiments, the stabilizing agent comprises 40 mM L-methionine.

[0281] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of arginine (e.g., L-arginine). In some embodiments, the pharmaceutical composition comprises greater than 1 mM arginine, greater than 2 mM arginine, greater than 3 mM arginine, or greater than 4 mM arginine. In other aspects, the pharmaceutical composition comprises up to 5 mM arginine, up to 6 mM arginine, up to 7 mM arginine, up to 8 mM arginine, up to 9 mM arginine, up to 10 mM arginine, or up to 200 mM arginine. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 10 mM, 2 mM to 8 mM, 4 mM to 6 mM, or 5 mM arginine.

[0282] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of L-arginine. In some embodiments, the pharmaceutical composition comprises greater than 1 mM L-arginine, greater than 2 mM L-arginine, greater than 3 mM L-arginine, or greater than 4 mM L-arginine. In other aspects, the pharmaceutical composition comprises up to 5 mM L-arginine, up to 6 mM L-arginine, up to 7 mM L-arginine, up to 8 mM L-arginine, up to 9 mM L-arginine, up to 10 mM L-arginine, or up to 200 mM L-arginine. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 10 mM, 2 mM to 8 mM, 4 mM to 6 mM, or 5 mM L-arginine.

[0283] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of glycine. In some embodiments, the pharmaceutical composition comprises greater than 1 mM glycine, greater than 2 mM glycine, greater than 3 mM glycine, or greater than 4 mM glycine. In other aspects, the pharmaceutical composition comprises up to 5 mM glycine, up to 6 mM glycine, up to 7 mM glycine, up to 8 mM glycine, up to 9 mM glycine, up to 10 mM glycine, or up to 200 mM glycine. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 10 mM, 2 mM to 8 mM, 4 mM to 6 mM, or 5 mM glycine.

[0284] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of L-glycine. In some embodiments, the pharmaceutical composition comprises greater than 1 mML-glycine, greater than 2 mML-glycine, greater than 3 mML-glycine, or greater than 4 mML-glycine. In other aspects, the pharmaceutical composition comprises up to 5 mML-glycine, up to 6 mML-glycine, up to 7 mML-glycine, up to 8 mML-glycine, up to 9 mML-glycine, up to 10 mML-glycine, or up to 200 mML-glycine. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 10 mM, 2 mM to 8 mM, 4 mM to 6 mM, or 5 mM L-glycine.

[0285] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of proline. In some embodiments, the pharmaceutical composition comprises greater than 1 mM proline, greater than 2 mM proline, greater than 3 mM proline, or greater than 4 mM proline. In other aspects, the pharmaceutical composition comprises up to 5 mM proline, up to 6 mM proline, up to 7 mM proline, up to 8 mM proline, up to 9 mM proline, up to 10 mM proline, or up to 200 mM proline. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 10 mM, 2 mM to 8 mM, 4 mM to 6 mM, or 5 mM proline.

[0286] The anti-IGF-1R antibody composition of the present invention may contain various concentrations of L-proline. In some embodiments, the pharmaceutical composition comprises greater than 1 mM L-proline, greater than 2 mM L-proline, greater than 3 mM L-proline, or greater than 4 mM L-proline. In other aspects, the pharmaceutical composition comprises up to 5 mM L-proline, up to 6 mM L-proline, up to 7 mM L-proline, up to 8 mM L-proline, up to 9 mM L-proline, up to 10 mM L-proline, or up to 200 mM L-proline. In other aspects, the pharmaceutical composition comprises 1 mM to 200 mM, 1 mM to 150 mM, 1 mM to 100 mM, 1 mM to 50 mM, 1 mM to 25 mM, 1 mM to 10 mM, 2 mM to 8 mM, 4 mM to 6 mM, or 5 mM L-proline.

[0287] surfactants One of the main stresses that proteins (e.g., antibodies) can encounter is interfacial stress (e.g., from the air / water interface in a liquid composition or the ice / water interface during freezing / thawing). Surfactants are commonly used to stabilize proteins in biopharmaceutical compositions under stress or long-term storage to prevent or minimize aggregation and / or particle formation. Examples of surfactants include (but are not limited to) anionic surfactants (e.g., ammonium lauryl sulfate, sodium lauryl sulfate, sodium lauryl ether sulfate, sodium myristyl ether sulfate, sodium dioctyl sulfosuccinate, perfluorooctane sulfonate, perfluorobutane sulfonate, alkyl-aryl ether phosphates, alkyl ether phosphates, carboxylates, sodium lauroyl sarcosinate, perfluorononanoate, perfluorooctanoate); cationic surfactants (e.g., octenidine dihydrochloride, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, benzyl chloride, dimethyl di(octadecyl)ammonium chloride, and di(octadecyl)dimethylammonium bromide); and zwitterionic surfactants (e.g., 3-[(3-cholamidopropyl)dimethylamino]-l -Propanesulfonates, cocamidopropylhydroxysulfonate, phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, lauryl dimethylamine oxide, and myristamine oxide); nonionic surfactants (e.g., polysorbates or Brij series); ethoxylates (e.g., fatty alcohol ethoxylates (e.g., octaethylene glycol monododecyl ether and pentaethylene glycol monododecyl ether), alkylphenol ethoxylates (e.g., nonylbenzene alcohol ether and Triton X-100); fatty acid ethoxylates, ethoxylated amines, and / or fatty acid amides (e.g., polyethoxylated tallow amine, cocamidopropylethanolamine, and cocamidopropyldiethanolamine); terminally capped ethoxylates (e.g., poloxamer); fatty acid esters of polyhydroxy compounds; fatty acid esters of glycerol (e.g., glyceryl monostearate and glyceryl monolaurate); fatty acid esters of sorbitol (e.g., Span (e.g., sorbitan monolaurate, sorbitan monostearate, and sorbitan tristearate) and Tween (e.g., Tween 20, Tween 40, Tween 60, and Tween 80); fatty acid esters of sucrose; alkyl polyglucosides (e.g., decyl glucoside, lauryl glucoside, and octyl glucoside); combinations thereof.

[0288] In some implementations, the surfactant is polysorbate 80 (PS80). PS80 is also known as polyoxyethylene (80) sorbitan monooleate.

[0289] In some embodiments, PS80 is present at concentrations of 0.001 to 1% (w / v), 0.001% to 0.5% (w / v), 0.01% to 0.5% (w / v), 0.01% to 0.1% (w / v), 0.01% to 0.05% (w / v), 0.01% to 0.04% (w / v), 0.01% (w / v), 0.02% (w / v), 0.03% (w / v), 0.04% (w / v), 0.05% (w / v), 0.06% (w / v), 0.07% (w / v), 0.08% (w / v), 0.09% (w / v), or 0.1% (w / v). In some embodiments, PS80 is present at a concentration of 0.001 to 1% (w / v). In some embodiments, PS80 is present at a concentration of 0.001% to 0.5% (w / v). In some embodiments, PS80 is present at a concentration of 0.01% to 0.5% (w / v). In some embodiments, PS80 is present at a concentration of 0.01% to 0.1% (w / v). In some embodiments, PS80 is present at a concentration of 0.01% to 0.05% (w / v). In some embodiments, PS80 is present at a concentration of 0.01% to 0.04% (w / v). In some embodiments, PS80 is present at a concentration of 0.01% (w / v). In some embodiments, PS80 is present at a concentration of 0.02% (w / v). In some embodiments, PS80 is present at a concentration of 0.03% (w / v). In some embodiments, PS80 is present at a concentration of 0.04% (w / v). In some embodiments, PS80 is present at a concentration of 0.05% (w / v). In some embodiments, PS80 is present at a concentration of 0.06% (w / v). In some embodiments, PS80 is present at a concentration of 0.07% (w / v). In some embodiments, PS80 is present at a concentration of 0.08% (w / v). In some embodiments, PS80 is present at a concentration of 0.09% (w / v). In some embodiments, PS80 is present at a concentration of about 0.1% (w / v).

[0290] In some implementations, the surfactant is polysorbate 20 (PS20). PS20 is also known as polyoxyethylene (20) sorbitan monolaurate.

[0291] In some embodiments, PS20 is present at concentrations of 0.001 to 1% (w / v), 0.001% to 0.5% (w / v), 0.01% to 0.5% (w / v), 0.01% to 0.1% (w / v), 0.01% to 0.05% (w / v), 0.01% to 0.04% (w / v), 0.01% (w / v), 0.02% (w / v), 0.03% (w / v), 0.04% (w / v), 0.05% (w / v), 0.06% (w / v), 0.07% (w / v), 0.08% (w / v), 0.09% (w / v), or 0.1% (w / v). In some embodiments, PS20 is present at a concentration of 0.001 to 1% (w / v). In some embodiments, PS20 is present at a concentration of 0.001 to 0.5% (w / v). In some embodiments, PS20 is present at a concentration of 0.01 to 0.5% (w / v). In some embodiments, PS20 is present at a concentration of 0.01 to 0.1% (w / v). In some embodiments, PS20 is present at a concentration of 0.01% to 0.05% (w / v). In some embodiments, PS20 is present at a concentration of 0.01% (w / v). In some embodiments, PS20 is present at a concentration of 0.02% (w / v). In some embodiments, PS20 is present at a concentration of 0.03% (w / v). In some embodiments, PS20 is present at a concentration of 0.04% (w / v). In some embodiments, PS20 is present at a concentration of 0.05% (w / v). In some embodiments, PS20 is present at a concentration of 0.06% (w / v). In some embodiments, PS20 is present at a concentration of 0.07% (w / v). In some embodiments, PS20 is present at a concentration of 0.08% (w / v). In some embodiments, PS20 is present at a concentration of 0.09% (w / v). In some embodiments, PS20 is present at a concentration of about 0.1% (w / v).

[0292] In some embodiments, the surfactant is poloxamer. Poloxamer is a nonionic triblock copolymer consisting of a central hydrophobic chain of polyoxypropylene (polypropylene oxide) with two hydrophilic chains side-attached to polyoxyethylene (poly(ethylene oxide)). Examples of poloxamer include (but are not limited to) poloxamer 188, poloxamer 407, poloxamer 184, poloxamer 124, or combinations thereof.

[0293] pH The pH of antibody formulations is crucial for ensuring their stability and efficacy. Low pH can cause antibody unfolding and aggregation, especially during processes such as freeze-thaw cycles. Maintaining optimal pH is necessary to minimize aggregation that can induce undesirable immunogenic responses in patients. Therefore, selecting appropriate pH and buffer systems is critical in antibody formulations and is specific to each antibody.

[0294] In some embodiments, the pH of the pharmaceutical composition is 4.8 to 6.5. In some embodiments, the pH of the pharmaceutical composition is 4.8 to 6.0. In some embodiments, the pH of the pharmaceutical composition is 4.5 to 6.0. In some embodiments, the pH of the pharmaceutical composition is 5.0 to 6.0. In some embodiments, the pH of the pharmaceutical composition is 4.5 to 5.9, 4.5 to 5.8, 4.5 to 5.7, 4.5 to 5.6, 4.5 to 5.5, 4.6 to 5.9, 4.6 to 5.8, 4.6 to 5.7, 4.6 to 5.6, 4.6 to 5.5, 4.7 to 6.0, 4.7 to 5.9, 4.7 to 5.8, 4.7 to 5.7, 4.7 to 5.6, 4.7 to 5.5, 4.8 to 6.5, 4.8 to 6.0, 4.8 to 5.9, 4.8 to 5.8, 4.8 to 5.7, 4.8 to 5.6, 4.8 to 5.5, 4.9 to 6.0, 4.9 to 5.9, or 4.9 to 5.8. 4.9 to 5.7, 4.9 to 5.6, 4.9 to 5.5, 5.0 to 5.9, 5.0 to 5.8, 5.0 to 5.7, 5.0 to 5.6, 5.0 to 5.5, 5.1 to 5.9, 5.1 to 5.8, 5.1 to 5.7, 5.1 to 5.6, 5.1 to 5.5, 5.2 to 5.9, 5.2 to 5.8, 5.2 to 5.7, 5.2 to 5.6, 5.2 to 5.5, 5.3 to 5.9, 5.3 to 5.8, 5.3 to 5.7, 5.3 to 5.6, 5.3 to 5.5, 5.4 to 5.9, 5.4 to 5.8, 5.4 to 5.7, 5.4 to 5.6, 5.4 to 5.5. In some embodiments, the pH of the stabilizing agent is 4.5 to 6.5. In some embodiments, the pH of the stabilizing agent is 4.8 to 6.5. In some embodiments, the pH of the stabilizing agent is 4.8 to 6.0. In some embodiments, the pH of the stabilizing agent is 5.0 to 6.0. In some embodiments, the pH of the stabilizing agent is 5.2 to 6.0. In some embodiments, the pH of the stabilizing agent is 5.2 to 6.5. In some embodiments, the pH of the stabilizing agent is 4.8 to 5.5. In some embodiments, the pH of the stabilizing agent is 5.5 to 6.5. In some embodiments, the pH of the stabilizing agent is 5.0 to 5.5. In some embodiments, the pH of the stabilizing agent is 5.5 to 6.0.

[0295] In some embodiments, the pH of the pharmaceutical composition is 4.5. In some embodiments, the pH of the pharmaceutical composition is 5.0. In some embodiments, the pH of the pharmaceutical composition is 5.5. In some embodiments, the pH of the pharmaceutical composition is 6.0. In some embodiments, the pH of the pharmaceutical composition is 4.5-6.0 (e.g., 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0). In some embodiments, the pH of the pharmaceutical composition is 5.0-6.0 (e.g., 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0). In some embodiments, the pH of the pharmaceutical composition is 4.5. In some embodiments, the pH of the pharmaceutical composition is 4.6. In some embodiments, the pH of the pharmaceutical composition is 4.7. In some embodiments, the pH of the pharmaceutical composition is 4.8. In some embodiments, the pH of the pharmaceutical composition is 4.9. In some embodiments, the pH of the pharmaceutical composition is 5.0. In some embodiments, the pH of the pharmaceutical composition is 5.1. In some embodiments, the pH of the pharmaceutical composition is 5.2. In some embodiments, the pH of the pharmaceutical composition is 5.3. In some embodiments, the pH of the pharmaceutical composition is 5.4. In some embodiments, the pH of the pharmaceutical composition is 5.5. In some embodiments, the pH of the pharmaceutical composition is 5.6. In some embodiments, the pH of the pharmaceutical composition is 5.7. In some embodiments, the pH of the pharmaceutical composition is 5.8. In some embodiments, the pH of the pharmaceutical composition is 5.9. In some embodiments, the pH of the pharmaceutical composition is 6.0. In some embodiments, the pH of the stabilizing agent is 6.1. In some embodiments, the pH of the stabilizing agent is 6.2. In some embodiments, the pH of the stabilizing agent is 6.3. In some embodiments, the pH of the stabilizing agent is 6.4. In some embodiments, the pH of the stabilizing agent is 6.5.

[0296] Stability of antibody preparations Monomers, high molecular weight (HMW) substances, low molecular weight (LMW) substances In some embodiments, the stabilized formulation is characterized by the amount of high molecular weight (HMW) aggregates. In some embodiments, the amounts of high molecular weight (HMW), monomers, and low molecular weight (LMW) substances are measured by SEC or SEC-UPLC. In some embodiments, the amount of high molecular weight substances (HMWS) in the stabilized formulation is less than 10% (e.g., less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%), as measured by SEC. In some embodiments, the amount of high molecular weight substances (HMWS) in the stabilized formulation is less than 5%, as measured by SEC. In some embodiments, the stability based on HMW or HMWS is based on the composition stored at 40°C for a period of time (e.g., 4 weeks).

[0297] In some embodiments, after storage at 5°C for at least 9 months, less than 5% of the IGF-1R antibody is present in the formulation as an HMW (Hypothetical Memory Meaning) substance. In some embodiments, after storage at 5°C for at least 9 months, less than 4% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 3% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 2% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 1.5% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 1% of the IGF-1R antibody is present in the formulation as an HMW substance.

[0298] In some embodiments, after storage at 25°C for at least 6 months, less than 5% of the IGF-1R antibody is present in the formulation as an HMW (Hypothetical Memory Meaning) substance. In some embodiments, after storage at 25°C for at least 6 months, less than 4% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 3% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 2% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 1.5% of the IGF-1R antibody is present in the formulation as an HMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 1% of the IGF-1R antibody is present in the formulation as an HMW substance.

[0299] In some embodiments, after storage at 5°C for at least 9 months, greater than 90% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 5°C for at least 9 months, greater than 95% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 5°C for at least 9 months, greater than 96% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 5°C for at least 9 months, greater than 97% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 5°C for at least 9 months, greater than 98% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 5°C for at least 9 months, greater than 99% of the IGF-1R antibody is present in the formulation as a monomeric substance.

[0300] In some embodiments, after storage at 25°C for at least 6 months, greater than 90% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 25°C for at least 6 months, greater than 95% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 25°C for at least 6 months, greater than 96% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 25°C for at least 6 months, greater than 97% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 25°C for at least 6 months, greater than 98% of the IGF-1R antibody is present in the formulation as a monomeric substance. In some embodiments, after storage at 25°C for at least 6 months, greater than 99% of the IGF-1R antibody is present in the formulation as a monomeric substance.

[0301] In some embodiments, after storage at 5°C for at least 9 months, less than 5% of the IGF-1R antibody is present in the formulation as an LMW (lumb bob) substance. In some embodiments, after storage at 5°C for at least 9 months, less than 4% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 3% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 2% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 1.5% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 5°C for at least 9 months, less than 1% of the IGF-1R antibody is present in the formulation as an LMW substance.

[0302] In some embodiments, after storage at 25°C for at least 6 months, less than 5% of the IGF-1R antibody is present in the formulation as an LMW (lumb bob) substance. In some embodiments, after storage at 25°C for at least 6 months, less than 4% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 3% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 2% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 1.5% of the IGF-1R antibody is present in the formulation as an LMW substance. In some embodiments, after storage at 25°C for at least 6 months, less than 1% of the IGF-1R antibody is present in the formulation as an LMW substance.

[0303] In some embodiments, the percentage of monomers is determined by size exclusion chromatography (SEC). In some embodiments, the percentage of high molecular weight molecular weight (HMW) is determined by size exclusion chromatography (SEC). In some embodiments, the percentage of low molecular weight molecular weight (LMW) is determined by size exclusion chromatography (SEC). Size exclusion ultra-high performance liquid chromatography (SEC-UPLC) is a purity analysis method for identifying, separating, and purifying proteins based on molecular size. SEC works by inhibiting the entry of large molecules into stationary particles arranged in rows along the inner surface of the SEC column. This causes larger particles to elute rapidly, while smaller molecules are retained in the SEC column for a longer period due to hydrophobic interactions with the adsorbent material. Here, separating pure monomers from high molecular weight (HMW) aggregates and low molecular weight (LMW) fragments is crucial for determining the stability and aggregation of the relevant compounds. Monomers that retain the highest percentage over time and under stress conditions indicate that the compound has greater stability.

[0304] Thermal and conformational stability In some embodiments, the initial denaturation temperature is above 56°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 57°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 58°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 59°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 60°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 61°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 62°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 63°C, as measured by DSC. In some embodiments, the initial denaturation temperature is above 64°C, as measured by DSC.

[0305] Differential scanning calorimetry (DSC) is a thermal analysis technique used to measure the difference in heat required to raise the temperature of a sample and a reference as a function of temperature. This technique quantifies several characteristics of a sample, including the measurement of glass transitions. Glass transitions occur with increasing temperature in amorphous solids. These transitions appear as steps in the baseline of the recorded DSC signal due to changes in the sample's heat capacity. The DSC is adjusted by superimposing a sinusoidal temperature change onto the fundamental heating rate. This allows for the separation of overlapping DSC effects by calculating reversible and non-reversible signals. Reversible heat flow is correlated with changes in specific heat capacity (glass transition), while non-reversible heat flow corresponds to time-dependent phenomena. This technique helps understand the thermal stability of protein samples and evaluate conformational differences between them.

[0306] Imaging capillary isoelectric focusing (iCIEF) Imaging capillary isoelectric focusing (iCIEF) is used to monitor the distribution of charge variants. The isoelectric point (pI) (an intrinsic property of a particular protein) is the pH at which a protein molecule carries no net charge. Under an external electric field, charge variants move along a continuous pH gradient formed by a carrier ampholyte and stop when the pH equals their pI. This technique is used for the characterization and quantification of protein charge variants.

[0307] In some embodiments, the shift in the charge spectrum can be measured by iCIEF as the relative percentage of the main peak, acidic peak, and / or basic peak. For example, a stable formulation may be one in which, after four weeks of storage at 40°C, the change in the acidic peak relative to the initial value increases by less than 40% (e.g., less than 38%, 36%, 34%, 32%, 30%, 28%, 26%, 24%, 22%, or less than 20%), as measured by iCIEF and quantified using chromatographic software. In some embodiments, a stable formulation is one in which, after four weeks of storage at 40°C, the percentage of the main peak decreases by less than 35% relative to the initial value (e.g., less than 34%, less than 33%, less than 32%, less than 31%, less than 30%, less than 29%, less than 28%, less than 27%, less than 26%, less than 25%, less than 24%, less than 23%, less than 22%, less than 21%, or less than 20%), as measured by iCIEF and quantified using chromatographic software. In some implementations, after 4 weeks at 40°C, the percentage of the area of ​​the basic peak of the stable formulation, as measured by iCIEF, decreases by less than 6.5% relative to the initial value (e.g., less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%).

[0308] In some embodiments, the acid peak increases by less than 50% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 45% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 40% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 35% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the acid peak increases by less than 30% after storage at 40°C for at least four weeks, as measured by iCIEF.

[0309] In some embodiments, the peak increase is less than 50% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the peak increase is less than 45% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the peak increase is less than 40% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the peak increase is less than 35% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the peak increase is less than 30% after storage at 40°C for at least four weeks, as measured by iCIEF.

[0310] In some embodiments, the basicity peak increases by less than 10% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the basicity peak increases by less than 8% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the basicity peak increases by less than 7% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the basicity peak increases by less than 6.5% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the basicity peak increases by less than 6% after storage at 40°C for at least four weeks, as measured by iCIEF. In some embodiments, the basicity peak increases by less than 5.5% after storage at 40°C for at least four weeks, as measured by iCIEF.

[0311] purity In some embodiments, after storage at 5°C for at least three months, the decrease in purity is less than 5%, less than 4%, less than 3%, or less than 2.5%. In some embodiments, the decrease in purity is less than 5% after storage at 5°C for at least three months. In some embodiments, the decrease in purity is less than 4% after storage at 5°C for at least three months. In some embodiments, the decrease in purity is less than 3% after storage at 5°C for at least three months. In some embodiments, the decrease in purity is less than 2% after storage at 5°C for at least three months. In some embodiments, the decrease in purity is less than 1% after storage at 5°C for at least three months.

[0312] In some embodiments, after storage at 25°C for at least three months, the decrease in purity is less than 5%, less than 4%, less than 3%, or less than 2.5%. In some embodiments, the decrease in purity is less than 5% after storage at 25°C for at least three months. In some embodiments, the decrease in purity is less than 4% after storage at 25°C for at least three months. In some embodiments, the decrease in purity is less than 3% after storage at 25°C for at least three months. In some embodiments, the decrease in purity is less than 2% after storage at 25°C for at least three months. In some embodiments, the decrease in purity is less than 1% after storage at 25°C for at least three months.

[0313] In some embodiments, after storage at 40°C for at least four weeks, the decrease in purity is less than 5%, less than 4%, less than 3%, or less than 2.5%. In some embodiments, the decrease in purity is less than 5% after storage at 40°C for at least four weeks. In some embodiments, the decrease in purity is less than 4% after storage at 40°C for at least four weeks. In some embodiments, the decrease in purity is less than 3% after storage at 40°C for at least four weeks. In some embodiments, the decrease in purity is less than 2% after storage at 40°C for at least four weeks. In some embodiments, the decrease in purity is less than 1% after storage at 40°C for at least four weeks.

[0314] Non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS-NR) is a capillary electrophoresis method that allows for the separation of proteins by size, driven by a high-voltage direct current electric field. This technique is a purity analysis method based on the electrophoretic mobility of proteins, where smaller proteins move faster and larger proteins move slower.

[0315] In some embodiments, caliper sodium dodecyl sulfate (Caliper-SDS) is used to evaluate the purity of the stabilized formulation. In some embodiments, caliper sodium dodecyl sulfate reduced (Caliper-SDS-R) is used to evaluate the purity of the stabilized formulation. In some embodiments, caliper sodium dodecyl sulfate non-reduced (Caliper-SDS-NR) is used to evaluate the purity of the stabilized formulation. In some embodiments, capillary sodium dodecyl sulfate (CE-SDS) is used to evaluate the purity of the stabilized formulation.

[0316] Appearance / Gathering Appearance is a visual confirmation of the specimen compared to the standard. The appearance of all specimens is evaluated for visible grain, sharpness, and color. A sharpness detector is used to shine light directly onto the specimen, and routine inspections are performed against black and white backgrounds. This technique measures stability.

[0317] In some embodiments, the clarity of the stabilized formulation is 24 NTU or less. In some embodiments, the clarity of the stabilized formulation is 20 NTU or less. In some embodiments, the clarity of the stabilized formulation is 20 NTU or less. In some embodiments, the clarity of the stabilized formulation is 18 NTU or less. In some embodiments, the clarity of the stabilized formulation is 16 NTU or less.

[0318] In some embodiments, after storage at 5°C for at least 9 months, the stabilized formulation has 5 or fewer visible particles. In some embodiments, after storage at 25°C for at least 6 months, the stabilized formulation has 5 or fewer visible particles. In some embodiments, after storage at 40°C for at least 2 weeks, the stabilized formulation has 5 or fewer visible particles.

[0319] In some embodiments, the stabilized formulation is free of particles after being stored at 5°C for at least 9 months. In some embodiments, the stabilized formulation is free of particles after being stored at 25°C for at least 6 months. In some embodiments, the stabilized formulation is free of particles after being stored at 40°C for at least 2 weeks.

[0320] Exemplary anti-IGF-1R antibody preparations In some embodiments, the pharmaceutical composition comprising the antibody or a variant thereof provided herein at a pH of 5 to 6 (e.g., pH 5.5) comprises sucrose, methionine, PS80 or PS20, and histidine (e.g., L-histidine). In some embodiments, the concentration of sucrose is 7 to 9% (w / v) (e.g., 8%). In some embodiments, the concentration of methionine is 5 to 15 mM (e.g., 10 mM). In some embodiments, the concentration of PS80 or PS20 is 0.01 to 0.05% (w / v) (e.g., 0.2%). In some embodiments, the concentration of the histidine buffer is 15 to 25 mM (e.g., 20 mM).

[0321] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof; (ii) a buffer solution at a concentration of 10-60 mM; (iii) sucrose at a concentration of 1-20% (w / v); (iv) a stabilizer or antioxidant at a concentration of 1-15 mM; and (v) a surfactant at a concentration of 0.001-1% (w / v). In some embodiments, the pharmaceutical composition further comprises a pH of 4.5 to 6.0. In some embodiments, the antibody is, for example, one of those antibodies provided herein (e.g., antibodies described in Tables 2-7).

[0322] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or its antigen-binding fragment (e.g., anti-IGF-1R antibodies as described in Tables 2-7) at a concentration of 10-300 mg / mL; (ii) a histidine buffer at a concentration of 10-60 mM; (iii) sucrose at a concentration of 1-20% (w / v); (iv) methionine or L-methionine at a concentration of 1-15 mM; and (v) polysorbate at a concentration of 0.001-1% (w / v). In some embodiments, the pharmaceutical composition further comprises a pH of 4.5 to 6.0. In some embodiments, the pH of the formulation is 4.8. In some embodiments, the pH of the formulation is 5.5.

[0323] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 10-200 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 10-40 mM; (iii) sucrose at a concentration of 1-10% (w / v); (iv) methionine or L-methionine at a concentration of 1-15 mM; and (v) polysorbate at a concentration of 0.01-0.1% (w / v).

[0324] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0325] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v).

[0326] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0327] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v).

[0328] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0329] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v).

[0330] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0331] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v).

[0332] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 100 mg / mL (e.g., an anti-IGF-1R antibody or a variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0333] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 100 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v).

[0334] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 100 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0335] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 100 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.02% (w / v).

[0336] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 150 mg / mL (e.g., an anti-IGF-1R antibody or a variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of about 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0337] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 150 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of about 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v).

[0338] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 150 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v).

[0339] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 150 mg / mL (e.g., the anti-IGF-1R antibody or variant thereof as described in Tables 2-7); (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v).

[0340] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of about 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of about 10 mM; and (v) polysorbate at a concentration of about 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the stabilized formulation of the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising V. L SEQ ID NO: 13 and V HSEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a 20 mM histidine buffer; (iii) 8% (w / v) sucrose; (iv) 10 mM methionine; and (v) 0.04% (w / v) polysorbate; wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, which contains V L SEQ ID NO: 13 and V H SEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a 20 mM histidine buffer; (iii) 8% (w / v) sucrose; (iv) 10 mM methionine; and (v) 0.02% (w / v) polysorbate; wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising V L SEQ ID NO: 13 and V H SEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a 20 mM histidine buffer; (iii) 8% (w / v) sucrose; (iv) 10 mM L-methionine; and (v) 0.04% (w / v) polysorbate; wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, which contains V L SEQ ID NO: 13 and V HSEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of about 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 25 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.

[0341] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of about 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 1 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 2; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 4; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 5 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 6; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 8; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 9 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 10; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of about 8% (w / v); (iv) methionine at a concentration of about 10 mM; and (v) polysorbate at a concentration of about 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain containing the amino acid sequence SEQ ID NO: 11 and a heavy chain or a variant thereof containing the amino acid sequence SEQ ID NO: 12; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising V. L SEQ ID NO: 13 and V HSEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a 20 mM histidine buffer; (iii) 8% (w / v) sucrose; (iv) 10 mM methionine; and (v) 0.04% (w / v) polysorbate; wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, which contains V L SEQ ID NO: 13 and V H SEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a 20 mM histidine buffer; (iii) 8% (w / v) sucrose; (iv) 10 mM methionine; and (v) 0.02% (w / v) polysorbate; wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, which contains V L SEQ ID NO: 13 and V H SEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a 20 mM histidine buffer; (iii) 8% (w / v) sucrose; (iv) 10 mM L-methionine; and (v) 0.04% (w / v) polysorbate; wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, which contains V L SEQ ID NO: 13 and V HSEQ ID NO: 14; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 92; or light chain SEQ ID NO: 93 and heavy chain SEQ ID NO: 94 or variants thereof; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 15 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 16; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 79 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 80; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 100 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 101; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5.

[0342] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain variable region comprising the amino acid sequence SEQ ID NO: 98 and a heavy chain variable region or a variant thereof comprising the amino acid sequence SEQ ID NO: 99; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 150 mg / mL, comprising a light chain variable region comprising the amino acid sequence SEQ ID NO: 98 and a heavy chain variable region or a variant thereof comprising the amino acid sequence SEQ ID NO: 99; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.

[0343] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 150 mg / mL, comprising a light chain comprising the amino acid sequence SEQ ID NO: 3 and a heavy chain or a variant thereof comprising the amino acid sequence SEQ ID NO: 83; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.04% (w / v); wherein the pH of the pharmaceutical composition is 5.5.

[0344] In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 50 mg / mL, comprising a light chain variable region comprising the amino acid sequence SEQ ID NO: 86 and a heavy chain variable region or a variant thereof comprising the amino acid sequence SEQ ID NO: 91; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of 0.02% (w / v); wherein the pH of the pharmaceutical composition is 5.5. In some embodiments, the pharmaceutical composition comprises: (i) an anti-IGF-1R antibody or an antigen-binding fragment thereof at a concentration of 150 mg / mL, comprising a light chain variable region comprising the amino acid sequence SEQ ID NO: 86 and a heavy chain variable region or a variant thereof comprising the amino acid sequence SEQ ID NO: 91; (ii) a histidine buffer at a concentration of 20 mM; (iii) sucrose at a concentration of 8% (w / v); (iv) L-methionine at a concentration of 10 mM; and (v) polysorbate at a concentration of about 0.04% (w / v); wh...

Claims

1. A stabilizing formulation comprising an anti-IGF-1R antibody or its antigen-binding fragment at a concentration of 25-250 mg / ml. The antibody comprises a heavy chain variable region comprising HCDR1 (SEQ ID NO: 53), HCDR2 (SEQ ID NO: 54), and HCDR3 (SEQ ID NO: 55), and a light chain variable region comprising LCDR1 (SEQ ID NO: 56), LCDR2 (SEQ ID NO: 57), and LCDR3 (SEQ ID NO: 58). 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. The stable formulation of claim 1 or 2, wherein the heavy chain variable region comprises SEQ ID NO: 14 and the light chain variable region comprises SEQ ID NO:

13.

4. The stable formulation according to any one of claims 1-3, wherein the antibody comprises the heavy chain of SEQ ID NO: 92 or SEQ ID NO: 94 and the light chain of SEQ ID NO:

93.

5. The stable formulation as claimed in any of the preceding claims, wherein the anti-IGF-1R antibody is present at a concentration between 25-200 mg / ml, 50-200 mg / ml, 75-180 mg / ml, or 100-150 mg.

6. The stable formulation of claim 5, wherein the anti-IGF-1R antibody is present at a concentration of 50 mg / ml.

7. The stable formulation of claim 5, wherein the anti-IGF-1R antibody is present at a concentration of 150 mg / ml.

8. The stable formulation as claimed in any of the preceding claims, wherein the pH is between 5.0-6.0, 5.2-6.0, or 5.2-6.

5.

9. The stable formulation as described in any of the preceding claims, wherein the pH is 5.

5.

10. The stable formulation as described in any of the preceding claims, wherein the formulation further comprises sucrose.

11. The stable formulation of claim 10, wherein sucrose is present at a concentration between 1-20% (w / v).

12. The stable formulation of claim 11, wherein sucrose is present at a concentration of 8% (w / v).

13. The stable formulation as claimed in any of the preceding claims, wherein the formulation further comprises a stabilizer.

14. The stabilizing agent of claim 13, wherein the stabilizer is methionine.

15. The stable formulation of claim 14, wherein methionine is present at a concentration between 5-40 mM, 15-20 mM, or 5-15 mM.

16. The stable formulation of claim 15, wherein methionine is present at a concentration of 10 mM.

17. The stable formulation as claimed in any of the preceding claims, wherein the composition further comprises a surfactant.

18. The stable formulation of claim 17, wherein the surfactant is polysorbate 80 or polysorbate 20.

19. The stable formulation of claim 18, wherein polysorbate 80 is present at a concentration between 0.001-1% (w / v), 0.005-0.5% (w / v), or 0.01-0.05% (w / v).

20. The stable formulation of claim 19, wherein polysorbate 80 is present at a concentration of 0.02% (w / v).

21. The stable formulation of claim 19, wherein polysorbate 80 is present at a concentration of 0.04% (w / v).

22. The stable formulation as described in any of the preceding claims, wherein the formulation further comprises a buffer.

23. The stabilizing formulation of claim 22, wherein the buffer is histidine buffer, acetate buffer, and / or glutamate buffer.

24. The stabilizing formulation of claim 23, wherein the concentration of the buffer, alone or in combination, is between 5-100 mM, 10-60 mM, or 15-40 mM.

25. The stable formulation of claim 24, wherein the concentration of the histidine buffer is 20 mM.

26. The stabilizing formulation of claim 22, wherein the buffer does not contain succinate.

27. A stable formulation comprising: Anti-IGF-1R antibody at a concentration of 50 mg / ml; 20 mM histidine buffer; 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 5.5; The antibody comprises HCDR1 of SEQ ID NO: 53, HCDR2 of SEQ ID NO: 54, HCDR3 of SEQ ID NO: 55, LCDR1 of SEQ ID NO: 56, LCDR2 of SEQ ID NO: 57, and LCDR3 of SEQ ID NO:

58.

28. A stable formulation comprising: Anti-IGF-1R antibody at a concentration of 150 mg / ml; 20 mM histidine buffer; 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 5.5; The antibody comprises HCDR1 of SEQ ID NO: 53, HCDR2 of SEQ ID NO: 54, HCDR3 of SEQ ID NO: 55, LCDR1 of SEQ ID NO: 56, LCDR2 of SEQ ID NO: 57, and LCDR3 of SEQ ID NO:

58.

29. The stable formulation of claim 27 or 28, wherein the 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. The stable formulation of claim 29, wherein the heavy chain variable region comprises SEQ ID NO: 14 and the light chain variable region comprises SEQ ID NO:

13.

31. The stable formulation of claim 29 or 30, wherein the anti-IGF-1R antibody comprises a heavy chain comprising SEQ ID NO: 92 and a light chain comprising SEQ ID NO:

93.

32. The stable formulation of claim 29 or 30, wherein the anti-IGF-1R antibody comprises a heavy chain comprising SEQ ID NO: 94 and a light chain comprising SEQ ID NO:

93.

33. The stable formulation as claimed in any of the preceding claims, wherein after storage at 40°C for at least 4 weeks, 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 is present in the formulation in the form of HMW substance.

34. The stable formulation as claimed in any of the preceding claims, wherein after being stored at 40°C for at least 4 weeks, at least 90%, at least 95%, at least 96%, at least 97%, or at least 98% of the IGF-1R antibody is present in the formulation in monomeric form.

35. A stable formulation as claimed in any of the preceding claims, wherein after being stored at 5°C for at least 9 months, less than 5% of the IGF-1R antibody is present in the formulation as HMW material.

36. The stable formulation as claimed in any of the preceding claims, wherein after being stored at 25°C for at least 6 months, less than 5% of the IGF-1R antibody is present in the form of HMW substance.

37. The stable formulation according to any one of claims 33-36, wherein the percentage of HMW substance or monomer is measured by size exclusion chromatography (SEC).

38. The stable formulation as described in any of the preceding claims, wherein the initial denaturation temperature is above 59°C, as measured by DSC.

39. The stable formulation as described in any of the preceding claims, wherein after storage at 40°C for at least four weeks, the acid peak increases by less than 40%, as measured by iCIEF.

40. The stable formulation as claimed in any of the preceding claims, wherein after storage at 40°C for at least four weeks, the percentage of the main peak decreases by less than 35%, as measured by iCIEF.

41. The stable formulation as described in any of the preceding claims, wherein after storage at 40°C for at least four weeks, the percentage of the basic peak decreases by less than 6.5%, as measured by iCIEF.

42. The stable formulation as described in any of the preceding claims, wherein the clarity of the composition is 18 NTU or less.

43. The stable formulation as claimed in any of the preceding claims, wherein the formulation is free of particles after being stored at 40°C for at least two weeks.

44. The stable formulation as claimed in any of the preceding claims, wherein after storage at 40°C for at least four weeks, the decrease in purity is less than 5%, less than 4%, less than 3%, or less than 2.5%.

45. The stable formulation as claimed in any of the preceding claims, wherein the weight osmotic concentration is between 280-380 mOsmol / kg or between 340-420 mOsmol / kg.

46. ​​The stable formulation as described in any of the preceding claims, wherein the formulation is stored at -25 to 25°C.

47. The stable formulation according to any one of claims 1-45, wherein the formulation is stored at 2 to 8°C.

48. A stable formulation as claimed in any of the preceding claims, wherein the formulation is suitable for intravenous, subcutaneous or intramuscular administration.

49. A stable formulation as claimed in any of the preceding claims, wherein the formulation is a liquid pharmaceutical composition or a lyophilized pharmaceutical composition.

50. A dosage form comprising a stable formulation as described in any one of the preceding claims, including vials, pre-filled syringes, or autoinjectors.

51. Use of the stable formulation of any one of the preceding claims for the treatment of a subject with thyroid-associated ophthalmopathy.

52. The use as described in claim 51, wherein the stabilizing agent is administered intravenously.

53. The use as described in claim 51, wherein the stabilizing agent is administered subcutaneously.

54. Use of the stabilizing agent according to any one of claims 1-47 for reducing the clinical activity score (CAS) of thyroid-associated ophthalmopathy (TAO) in a subject, comprising administering the stabilizing agent.

55. The use as described in any one of claims 51-54, wherein the diplopia of the treated subject is reduced.

56. Use of the stable formulation of any one of claims 51-55 for treating a subject with thyroid-associated ophthalmopathy (TAO) or reducing its severity, comprising administering said stable formulation. Treatment using the pharmaceutical composition reduced bulging of one eye by at least 2 mm; The other eye (or the contralateral eye) does not show any deterioration of 2 mm or more; and The subject's CAS was reduced to one (1) or zero (0).

57. Use of the stable formulation of any one of claims 1-49 for improving the quality of life of a subject suffering from thyroid-associated ophthalmopathy (TAO, also known as Graves' ophthalmopathy / Graves' orbital lesion), comprising administering the stable formulation of any one of claims 206-245.

58. The use as claimed in claim 57, wherein the quality of life is measured by the Graves Eye Disease Quality of Life (GO-QoL) assessment or its visual function or appearance subscale.

59. The use as claimed in claim 58, wherein the treatment results in an improvement in the functional subscale of the GO-QoL.

60. The use as claimed in claim 58, wherein the treatment results in an improvement in the appearance subscale of the GO-QoL.

61. The use of the stable formulation of any one of claims 1-49 for treating diplopia or reducing the severity of diplopia in a subject suffering from thyroid-associated ophthalmopathy (TAO), comprising administering the stable formulation of any one of claims 1-49.

62. The use as claimed in claim 61, wherein the diplopia is persistent diplopia.

63. The use as described in claim 61, wherein the diplopia is non-continuous diplopia.

64. The use as claimed in claim 61, wherein the diplopia is intermittent diplopia.

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