Methods of treating sarcoidosis with a TNF-Αlpha antibody and associated compositions and methods

Abstract

Provided are compositions comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules, and associated methods. In some embodiments, provided are methods for treating or preventing sarcoidosis and / or granuloma size or formation in patients in need thereof. In some embodiments, an outcome of the methods of the present technology is increased relative to the same method comprising use of a corticosteroid.

Description

METHODS OF TREATING SARCOIDOSIS WITH A TNF-ALPHA ANTIBODY AND ASSOCIATED COMPOSITIONS AND METHODSCROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims the benefit of U. S. Provisional Patent Application No. 63 / 800,706, filed May 6, 2025, of U. S. Provisional Patent Application No.63 / 790,840, filed April 18, 2025, and of U. S. Provisional Patent Application No.63 / 714,749, filed October 31, 2024, all of which applications are incorporated herein by reference in their entiretyINCORPORATION BY REFERENCE OF SEQUENCE LISTING

[0002] The application contains a Sequence Listing which has been submitted electronically in. XML format and is hereby incorporated by reference in its entirety. Said. XML copy, created on October 22, 2025, is named “18Z2-414457-WO.xml” and is 33,705 bytes in size. The sequence listing contained in this. XML file is part of the specification and is hereby incorporated by reference herein in its entirety. BACKGROUND

[0003] Sarcoidosis is a chronic, multisystem inflammatory disorder of unknown etiology that is characterized by the presence of non-caseating epithelioid granulomas, accompanied by infiltration of mononuclear cells and destruction of microarchitecture. This rare disease affects the skin, eye, heart, and central nervous system, and >90% of cases involve the lungs. Subjects with lung manifestations may progress to loss of lung function, and immune-modulating therapy may be beneficial in these cases. Current treatment options are suboptimal due to adverse side effects, limited efficacy, or inability to access the most effective treatments.

[0004] Macrophage-derived tumor necrosis factor a (TNFa) participates in the induction and maintenance of granulomas, and high levels of TNFa (and high levels of TNFa released from alveolar macrophages) seem to correlate with disease progression. In chronic sarcoidosis, prevention of granuloma formation and limitation of tissue injury and fibrosis are the goals of therapy. In some cases, these may be achieved through targeted immunosuppression of pro- inflammatory cytokines such as TNFa. Infliximab is a monoclonal antibody (mAb) targeting TNFa that is being used off-label to treat sarcoidosis. In a randomized controlled study of subjects with chronic refractory pulmonary sarcoidosis, low- and high-dose intravenous (IV) infusion of infliximab produced a 2.5% increase in predicted forced vital capacity at 24 weeks. Notably, other TNF inhibitors have been shown to be ineffective for the treatment of sarcoidosis or may paradoxically cause sarcoidosis-like drug reactions.

[0005] First-line agents include corticosteroids (tapered over time), followed by second- and third-line immunomodulatory agents, which are carefully selected to mitigate side effects, particularly related to systemic steroid exposure. Although corticosteroids are effective in resolving the granulomatous inflammation in sarcoidosis, up to 20% of subjects treated with systemic steroid therapy continue to exhibit a persistent granulomatous inflammatory process, with progression to irreversible tissue remodeling and fibrosis.

[0006] In subjects with advanced or severe refractory sarcoidosis who do not respond to conventional immunosuppressive treatment, TNFa inhibitors are recommended. However, there has been limited pharmacokinetic analysis of TNFa inhibitor use in sarcoidosis. As such, there remains a need to conduct dose range finding to determine a safe and efficacious dose regimen for the sarcoidosis population. SUMMARY

[0007] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time.

[0008] The present technology comprises a method of reducing or tapering concurrent corticosteriod use in a subject with sarcoidosis relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time.

[0009] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King's Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

[0010] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

[0011] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

[0012] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acidmolecules about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0013] The present technology comprises a method of reducing or tapering concurrent corticosteriod use in a subject with sarcoidosis relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0014] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a quality of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ), a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical toYA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0015] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfthCDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0016] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0017] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks.

[0018] The present technology comprises a method of reducing or tapering concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks.

[0019] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to a control or baseline.

[0020] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline.

[0021] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acidmolecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

[0022] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0023] The present technology comprises a method of reducing or tapering concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis,the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0024] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acidsequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0025] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0026] The present technology comprises a method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequenceat least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (ix) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0027] In some embodiments, the dose is about 2 mg / kg of the composition.

[0028] In some embodiments, the dose is about 4 mg / kg of the composition.

[0029] In some embodiments, the method comprises administering to the subject about 2 mg / kg of the composition once every 2 weeks for the first period of time.

[0030] In some embodiments, the method comprises administering to the subject about 4 mg / kg of the composition once every 2 weeks for the first period of time.

[0031] In some embodiments, the method comprises administering to the subject about 2 mg / kg of the composition once every 4 weeks for the first period of time.

[0032] In some embodiments, the method comprises administering to the subject about 4 mg / kg of the composition once every 4 weeks for the first period of time.

[0033] In some embodiments, the anti-TNFa antibody comprises a complementarity determining region (CDR) 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, or 15, or YA.

[0034] In some embodiments, the anti-TNFa antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16.

[0035] In some embodiments, the anti-TNFa antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

[0036] In some embodiments, the anti-TNFa antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16, and wherein the anti-TNFa antibody comprises avariable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

[0037] In some embodiments, the anti-TNFa antibody comprises an asparagine-linked glycosylation site within a constant Fc region on at least one of the heavy chains.

[0038] In some embodiments, the anti-TNFa antibody comprises an asparagine-linked glycosylation site within the constant Fc region on both of the heavy chains.

[0039] In some embodiments, the anti-TNFa antibody is sialylated at Asn 297.

[0040] In some embodiments, the anti-TNFa antibody comprises no N-Glycolylneuraminic acid (Neu5Gc).

[0041] In some embodiments, the anti-TNFa antibody is an immunoglobulin G (IgG) antibody.

[0042] In some embodiments, the IgG antibody is an IgG 1 antibody.

[0043] In some embodiments, the IgG 1 antibody comprises a kappa isotype.

[0044] In some embodiments, the anti-TNFa antibody is a chimeric antibody.

[0045] In some embodiments, the anti-TNFa antibody comprises a C-terminal lysine on at least one of the heavy chains.

[0046] In some embodiments, the anti-TNFa antibody comprises a C-terminal lysine on both of the heavy chains.

[0047] In some embodiments, the C-terminal lysine is not clipped.

[0048] In some embodiments, the composition is administered by an infusion.

[0049] In some embodiments, the infusion is an intravenous (IV) infusion.

[0050] In some embodiments, the infusion is administered over a period of at least about 2 hours.

[0051] In some embodiments, the first period of time is about 6 weeks to about 24 weeks.

[0052] In some embodiments, the first period of time is about 8 weeks.

[0053] In some embodiments, the first period of time is about 12 weeks.

[0054] In some embodiments, the subject receives a cumulative dose of about 6 mg / kg to about 30 mg / kg of the composition during the first period of time.

[0055] In some embodiments, the subject receives a cumulative dose of about 6 mg / kg of the composition during the first period of time.

[0056] In some embodiments, the subject receives a cumulative dose of about 8 mg / kg of the composition during the first period of time.

[0057] In some embodiments, the subject receives a cumulative dose of about 12 mg / kg of the composition during the first period of time.

[0058] In some embodiments, the subject receives a cumulative dose of about 16 mg / kg of the composition during the first period of time.

[0059] In some embodiments, the subject is administered at least 3 doses of the composition.

[0060] In some embodiments, the subject is administered at least 4 doses of the composition.

[0061] In some embodiments, the subject is administered at least 6 doses of the composition.

[0062] In some embodiments, the subject is administered at least 3 doses over a 12-week period of time.

[0063] In some embodiments, the subject is administered at least 6 doses over a 12-week period of time.

[0064] In some embodiments, administration of the composition reduces a level of one or more transcripts selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL6), interleukin 2 receptor (I L2R), tumor necrosis factor alpha (TNFa), C-Reactive Protein (CRP), interleukin 1B (IL1 B), interleukin 12 (IL12), interleukin 18 (IL18), interferon gamma (IFNG), interleukin 8 (IL8), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB protooncogene (JunB), mitogen-activated protein kinase (MKP1 ), TNF alpha induced protein 1 (TNFAIP1), TNF alpha induced protein 2 (TNFAIP2), TNF alpha induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome coxidase subunit II (COX2), interleukin 32 (IL32), intercellular adhesion molecule 1 (ICAM-1), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1 A member 1 (SCGB1 A1 ), serum amyloid A1 (SAA1 ), and vascular adhesion molecule 1 (VCAM-1), relative to a control.

[0065] In some embodiments, the level of the one or more transcripts is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0066] In some embodiments, administration of the composition reduces a level of one or more proteins selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL-6), interleukin 2 receptor (IL-2R), tumor necrosis factor alpha (TNF-o), C-Reactive Protein (CRP), interleukin 1 B (IL-1 B), interferon gamma (IFN-y), interleukin 8 (IL-8), interleukin 12 (IL-12), interleukin 18 (IL-18), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JUNB), mitogen-activated protein kinase phosphatase 1 (MKP-1), TNF alpha-induced protein 1 (TNFAIP1), TNF alpha-induced protein 2 (TNFAIP2), TNF alpha-induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL-32), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT 1 ), secretoglobin family 1 A member 1 (SCGB1A1), serum amyloid A1 (SAA1), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) relative to a control.

[0067] In some embodiments, the level of the one or more proteins is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0068] In some embodiments, administration of the composition improves a Forced Vital Capacity (FVC) measurement in the subject relative to the control or baseline.

[0069] In some embodiments, the FVC measurement is improved by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0070] In some embodiments, administration of the composition improves a King’s Sarcoidosis Questionnaire (KSQ) score in the subject relative to the control or baseline.

[0071] In some embodiments, the KSQ score is increased by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control.

[0072] In some embodiments, administration of the composition improves a Leicester Cough Questionnaire (LCQ) score in the subject relative to the control or baseline.

[0073] In some embodiments, the LCQ score is increased by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 points relative to the control or baseline.

[0074] In some embodiments, administration of the composition improves a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

[0075] In some embodiments, the STQ score is reduced by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0076] In some embodiments, administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP) in the subject relative to the control or baseline.

[0077] In some embodiments, the CRP level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0078] In some embodiments, administration of the composition decreases or stabilizes a level of Angiotensin Converting Enzyme (ACE) in the subject relative to the control or baseline.

[0079] In some embodiments, the ACE level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0080] In some embodiments, administration of the composition decreases or stabilizes a level of Soluble lnterleukin-2 receptor (slL-2) in the subject relative to the control or baseline.

[0081] In some embodiments, the ACE level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0082] In some embodiments, administration of the composition decreases or stabilizes a level of Interleukin-6 (IL-6) in the subject relative to the control or baseline.

[0083] In some embodiments, the IL-6 level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0084] In some embodiments, administration of the composition decreases or stabilizes a level of Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

[0085] In some embodiments, the sTNFa level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0086] In some embodiments, administration of the composition improves a Patient Global Assessment (PGA) score in the subject relative to the control or baseline.

[0087] In some embodiments, the PGA score is increased by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

[0088] In some embodiments, administration of the composition improves a Fatigue Assessment Scale (FAS) score in the subject relative to the control or baseline.

[0089] In some embodiments, the FAS score is reduced by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

[0090] In some embodiments, administration of the composition improves a Modified Medical Research Council (mMRC) Dyspnea Scale score in the subject relative to the control or baseline.

[0091] In some embodiments, the mMRC Dyspnea score is improved by at least about 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

[0092] In some embodiments, administration of the composition improves a 6 Minute Walk Distance (6MWD) in the subject relative to the control or baseline.

[0093] In some embodiments, the 6MWD is improved by about 3 min, 5 min, 10 min, 20 min, or 30 min relative to the control or baseline.

[0094] In some embodiments, administration of the composition improves a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

[0095] In some embodiments, administration of the composition improves a Short Form Survey (SF-36) score in the subject relative to the control or baseline.

[0096] In some embodiments, the SF-36 score is increased by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control or baseline.

[0097] In some embodiments, administration of the composition reduces corticosteriod use in the subject relative to the control or baseline.

[0098] In some embodiments, corticosteriod use in the subject is reduced by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

[0099] In some embodiments, the subject has one or more of acute sarcoidosis, chronic sarcoidosis, progressive sarcoidosis, pulmonary sarcoidosis, remitting sarcoidosis, refractory sarcoidosis, advanced sarcoidosis, ocular sarcoidosis, cutaneous sarcoidosis, or neurosarcoidosis.

[0100] In some embodiments, the subject has received an anti-inflammatory medication.

[0101] In some embodiments, the subject is receiving an anti-inflammation medication.

[0102] In some embodiments, the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline, thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab.

[0103] In some embodiments, the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone.

[0104] In some embodiments, administration of the composition does not result in adverse events (AEs) in the subject relative to control or baseline.

[0105] In some embodiments, administration of the composition does not result in treatment-emergent adverse events (TEAEs) in the subject relative to the control.

[0106] In some embodiments, administration of the composition does not result in serious adverse events (SAEs) in the subject relative to the control.

[0107] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose of about 0.5 mg / kg to about 6.0 mg / kg of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules about once every four weeks for a first period of time.

[0108] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose of about 0.5 mg / kg to about 6.0 mg / kg of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules about once every two weeks for a first period of time.

[0109] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose of about 0.5 mg / kg to about 6.0mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every four weeks for a first period of time.

[0110] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose of about 0.5 mg / kg to about 6.0 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every two weeks for a first period of time.

[0111] In some embodiments, the first period of time is about 6 weeks to about 24 weeks.

[0112] In some embodiments, the first period of time is about 8 weeks.

[0113] In some embodiments, the first period of time is about 12 weeks.

[0114] In some embodiments, the first period of time is about 24 weeks.

[0115] In some embodiments, the first dose is about 2 mg / kg of the composition.

[0116] In some embodiments, the first dose is about 4 mg / kg of the composition.

[0117] In some embodiments, the anti-TNFa antibody comprises a complementarity determining region (CDR) 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, or 15, or YA.

[0118] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every four weeks for a first period of time, and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ IDNO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0119] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every two weeks for a first period of time; and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at leastabout 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0120] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 4 mg / kg of the composition administered once every four weeks for a first period of time; and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0121] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprisingan anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 4 mg / kg of the composition administered once every two weeks for a first period of time; and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0122] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every four weeks for a first period of time; and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acidsequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0123] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every two weeks for a first period of time; and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%,or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0124] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 4 mg / kg of the composition administered once every four weeks for a first period of time; and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0125] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the methodcomprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 4 mg / kg of the composition administered once every two weeks for a first period of time; and the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0126] In some embodiments, the method comprises administering to the subject a second dose of the composition for a second period of time.

[0127] In some embodiments, the second period of time is about 6 weeks to about 16 weeks.

[0128] In some embodiments, the second period of time is about 8 weeks.

[0129] In some embodiments, the second period of time is about 12 weeks.

[0130] In some embodiments, the second dose comprises about 1 mg / kg to about 5 mg / kg.

[0131] In some embodiments, the second dose is about 2 mg / kg.

[0132] In some embodiments, the second dose is about 4 mg / kg.

[0133] In some embodiments, the second dose is about two times greater than the first dose.

[0134] In some embodiments, the administration frequency of the second dose comprises the same administration frequency of the first dose.

[0135] In some embodiments, the administration frequency of the second dose consists of the same administration frequency of the first dose.

[0136] In some embodiments, the first dose and the second dose are each administered about once every four weeks.

[0137] In some embodiments, the second dose is about the same dose as the first dose.

[0138] In some embodiments, the second dose is the same dose as the first dose.

[0139] In some embodiments, the first dose and the second dose are about 2 mg / kg.

[0140] In some embodiments, the administration frequency of the second dose is about two times greater than the administration frequency of the first dose.

[0141] In some embodiments, the first dose is administered about once every four weeks and the second dose is administered about once every two weeks.

[0142] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every four weeks for a first period of time; and the second dose comprising (i) about 2 mg / kg of the composition administered once every two weeks, or (iii) about 4 mg / kg of the composition administered once every 4 weeks, for a second period of time.

[0143] The present technology comprises method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a compositioncomprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every four weeks for a first period of time; and the second dose comprising (i) about 2 mg / kg of the composition administered once every two weeks, or (iii) about 4 mg / kg of the composition administered once every 4 weeks, for a second period of time.

[0144] In some embodiments, the first period of time is about 6 weeks to about 12 weeks.

[0145] In some embodiments, the first period of time is about 8 weeks.

[0146] In some embodiments, the first period of time is about 12 weeks.

[0147] In some embodiments, the second period of time is about 6 weeks to about 12 weeks.

[0148] In some embodiments, the second period of time is about 8 weeks.

[0149] In some embodiments, the second period of time is about 12 weeks.

[0150] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every four weeks for a first period of time; and the second dose comprising (i) about 2 mg / kg of the composition administered once every two weeks, or (iii) about 4 mg / kg of the composition administered once every 4 weeks, for a second period of time; the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence atleast about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0151] In some embodiments, the present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every two weeks for a first period of time; and the second dose comprising (i) about 2 mg / kg of the composition administered once every two weeks, or (iii) about 4 mg / kg of the composition administered once every four weeks, for a second period of time; the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) aneleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0152] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the method comprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every four weeks for a first period of time; the second dose comprising (i) about 2 mg / kg of the composition administered once every two weeks, or (iii) about 4 mg / kg of the composition administered once every four weeks, for a second period of time; the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0153] The present technology comprises a method of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control, the methodcomprising administering to the subject a first dose and a second dose of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules; the first dose comprising about 2 mg / kg of the composition administered once every two weeks for a first period of time; the second dose comprising (i) about 2 mg / kg of the composition administered once every two weeks, or (iii) about 4 mg / kg of the composition administered once every four weeks, for a second period of time; the anti-TNFa antibody comprising: (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5; (iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii)a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

[0154] The present technology comprises a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every four weeks for about 12 weeks, wherein the anti-TNFa antibody comprises: (i) a first CDR comprising the amino acid sequence of SEQ ID NO: 3; (ii) a second CDR comprising the amino acid sequence of SEQ ID NO: 4; (iii) a third CDR comprising the amino acid sequence of SEQ ID NO: 5; (iv) a fourth CDR comprising theamino acid sequence of SEQ ID NO: 6; (v) a fifth CDR comprising the amino acid sequence of SEQ ID NO: 7; (vi) a sixth CDR comprising the amino acid sequence of SEQ ID NO: 8; (vii) a seventh CDR comprising the amino acid sequence of SEQ ID NO: 10; (viii) an eighth CDR comprising the amino acid sequence of YA; (ix) a ninth CDR comprising the amino acid sequence of SEQ ID NO: 12; (x) a tenth CDR comprising the amino acid sequence of SEQ ID NO: 13; (xi) an eleventh CDR comprising the amino acid sequence of SEQ ID NO: 14; and (xii) a twelfth CDR comprising the amino acid sequence of SEQ ID NO: 15.

[0155] In some embodiments, the methods further comprise administering (c) a third dose of about 4 mg / kg of the composition about once every two weeks, for a third period of time.

[0156] In some embodiments, the third period of time is at least about 24 weeks.

[0157] In some embodiments, the anti-TNFa antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16.

[0158] In some embodiments, the anti-TNFa antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

[0159] In some embodiments, the anti-TNFa antibody comprises an asparagine-linked glycosylation site within a constant Fc region on at least one of the heavy chains.

[0160] In some embodiments, the anti-TNFa antibody comprises an asparagine-linked glycosylation site within the constant Fc region on both of the heavy chains.

[0161] In some embodiments, the anti-TNFa antibody is sialylated at Asn 297.

[0162] In some embodiments, the anti-TNFa antibody comprises no N-Glycolylneuraminic acid (Neu5Gc).

[0163] In some embodiments, the anti-TNFa antibody is an immunoglobulin G (IgG) antibody.

[0164] In some embodiments, the IgG antibody is an IgG 1 antibody.

[0165] In some embodiments, the IgG 1 antibody comprises a kappa isotype.

[0166] In some embodiments, the anti-TNFa antibody is a chimeric antibody.

[0167] In some embodiments, the anti-TNFa antibody comprises a C-terminal lysine on at least one of the heavy chains.

[0168] In some embodiments, the anti-TNFa antibody comprises a C-terminal lysine on both of the heavy chains.

[0169] In some embodiments, the C-terminal lysine is not clipped.

[0170] In some embodiments, the composition is administered by an infusion.

[0171] In some embodiments, the infusion is an intravenous (IV) infusion.

[0172] In some embodiments, the infusion is administered over a period of at least about 2 hours.

[0173] In some embodiments, the infusion is administered over a period of about 2 hours.

[0174] In some embodiments, the subject receives a cumulative dose of about 6 mg / kg of the composition during the first period of time.

[0175] In some embodiments, the subject receives a cumulative dose of about 8 mg / kg of the composition during the first period of time.

[0176] In some embodiments, the subject receives a cumulative dose of about 16 mg / kg of the composition during the first period of time.

[0177] In some embodiments, the subject receives a cumulative dose of about 10 mg / kg to about 16 mg / kg of the composition during the second period of time.

[0178] In some embodiments, the subject receives a cumulative dose of about 10 mg / kg of the composition during the second period of time.

[0179] In some embodiments, the subject receives a cumulative dose of about 12 mg / kg of the composition during the second period of time.

[0180] In some embodiments, the subject receives a cumulative dose of about 14 mg / kg of the composition during the second period of time.

[0181] In some embodiments, the subject receives a cumulative dose of about 16 mg / kg of the composition during the second period of time.

[0182] In some embodiments, the subject receives a cumulative dose of about 28 mg / kg of the composition.

[0183] In some embodiments, the subject is administered a cumulative dose of about 30 mg / kg to about 60 mg / kg of the composition.

[0184] In some embodiments, the subject is administered a cumulative dose of about 46 mg / kg of the composition.

[0185] In some embodiments, the subject is administered a cumulative dose of about 48 mg / kg of the composition.

[0186] In some embodiments, the subject is administered a cumulative dose of about 50 mg / kg of the composition.

[0187] In some embodiments, the subject is administered a cumulative dose of about 52 mg / kg of the composition.

[0188] In some embodiments, the subject is administered at least 3 doses of the composition.

[0189] In some embodiments, the subject is administered at least 4 doses of the composition.

[0190] In some embodiments, the subject is administered at least 6 doses of the composition.

[0191] In some embodiments, the subject is administered at least 7 doses of the composition.

[0192] In some embodiments, the at least 3 doses are administered over a 4-week period of time.

[0193] In some embodiments, the at least 3 doses are administered over an 8-week period of time.

[0194] In some embodiments, the at least 3 doses are administered over a 12-week period of time.

[0195] In some embodiments, the at least 4 doses are administered over a 9-week period of time.

[0196] In some embodiments, the at least 4 doses are administered over a 10-week period of time.

[0197] In some embodiments, the at least 4 doses are administered over an 11-week period of time.

[0198] In some embodiments, the at least 4 doses are administered over a 12-week period of time.

[0199] In some embodiments, the at least 6 doses are administered over a 10-week period of time.

[0200] In some embodiments, the at least 6 doses are administered over a 12-week period of time.

[0201] In some embodiments, the at least 6 doses are administered over a 13-week period of time.

[0202] In some embodiments, the at least 6 doses are administered over a 16-week period of time.

[0203] In some embodiments, the at least 6 doses are administered over a 17-week period of time.

[0204] In some embodiments, the at least 6 doses are administered over a 20-week period of time.

[0205] In some embodiments, the at least 7 doses are administered over a 12-week period of time.

[0206] In some embodiments, the at least 7 doses are administered over a 15-week period of time.

[0207] In some embodiments, the at least 7 doses are administered over a 21-week period of time.

[0208] In some embodiments, the at least 7 doses are administered over a 28-week period of time.

[0209] In some embodiments, the at least 7 doses are administered over a 24-week period of time.

[0210] In some embodiments, administration of the composition reduces a level of one or more transcripts selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 ( I L6), interleukin 2 receptor (IL2R), tumor necrosis factoralpha (TNFa), C-Reactive Protein (CRP), interleukin 1B (IL1 B), interleukin 12 (IL12), interleukin 18 (IL18), interferon gamma (IFNG), interleukin 8 (ILS), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB protooncogene (JunB), mitogen-activated protein kinase (MKP1 ), TNF alpha induced protein 1 (TNFAIP1), TNF alpha induced protein 2 (TNFAIP2), TNF alpha induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL32), intercellular adhesion molecule 1 (ICAM-1), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1 A member 1 (SCGB1 A1 ), serum amyloid A1 (SAA1 ), and vascular adhesion molecule 1 (VCAM-1), relative to a control.

[0211] In some embodiments, the level of the one or more transcripts is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0212] In some embodiments, administration of the composition reduces a level of one or more proteins selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL-6), interleukin 2 receptor (IL-2R), tumor necrosis factor alpha (TNF-a), C-Reactive Protein (CRP), interleukin 1 B (IL-1 B), interferon gamma (IFN-y), interleukin 8 (IL-8), interleukin 12 (IL-12), interleukin 18 (IL-18), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JUNB), mitogen-activated protein kinase phosphatase 1 (MKP-1), TNF alpha-induced protein 1 (TNFAIP1), TNF alpha-induced protein 2 (TNFAIP2), TNF alpha-induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL-32), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT 1 ), secretoglobin family 1 A member 1 (SCGB1A1), serum amyloid A1 (SAA1), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) relative to a control.

[0213] In some embodiments, the level of the one or more proteins is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0214] In some embodiments, wherein administration of the composition increases one or more of a Forced Vital Capacity (FVC) measurement, a Forced Expiratory Volume in 1 second (FEV1) measurement, a Leicester Cough Questionnaire (LCQ) score, a Short Form 36 Health Survey (SF-36) score, a King’s Sarcoidosis Questionnaire (KSQ) score, a Steroid-toxicity scale (STS) score, or a 6-minute walk test (6MWT) distance relative to a control.

[0215] In some embodiments, the FVC measurement is increased by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0216] In some embodiments, the FEV1 measurement is increased by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0217] In some embodiments, the LCQ score is increased by at least about 0.3, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 points relative to the control.

[0218] In some embodiments, the SF-36 score is increased by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control.

[0219] In some embodiments, the KSQ score is increased by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control.

[0220] In some embodiments, the KSQ score is a KSQ General Health Status Module or a KSQ lung score.

[0221] In some embodiments, the STS score is increased by at least 1, 2, 3, 4, 5, or 6 points relative to the control.

[0222] In some embodiments, the 6MWT distance is increased by at least 10m, 20m, 30m, 40m, 50m, 60m, 70m, 80m, 90m, 100m, 125m, 150m, 175m, 200m, 250m, 300m, 350m, 400m, 450m, or 500m relative to the control.

[0223] In some embodiments, administration of the composition reduces one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, Modified Medical Research Council (mMRC) Dyspnea Scale score, a Saint George's Respiratory Questionnaire (SGRQ) score, or a Borg’s CR10 dyspnea score relative to a control.

[0224] In some embodiments, the PGA score is reduced by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points relative to the control.

[0225] In some embodiments, the FAS score is reduced by at least about 1, 2, 3, or 4 points relative to a control.

[0226] In some embodiments, the mMRC Scale score is reduced by at least about 1, 2, 3, or 4 grades relative to the control.

[0227] In some embodiments, the SGRQ score is reduced by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control.

[0228] In some embodiments, the Borg's CR10 dyspnea score is reduced by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points relative to the control.

[0229] In some embodiments, administration of the composition reduces a need for an anti-inflammatory medication relative to a control.

[0230] In some embodiments, the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline,thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab.

[0231] In some embodiments, the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone.

[0232] In some embodiments, the reduced need for anti-inflammatory medication comprises a reduction in frequency of, dosage of, or duration of administration of the anti-inflammatory medication.

[0233] In some embodiments, administration of the composition reduces a granuloma formation or a granuloma size in the subject by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%, relative to a control.

[0234] In some embodiments, the granuloma is a skin granuloma, a lung granuloma, a lymph node granuloma, an ocular granuloma, a liver granuloma, a spleen granuloma, a cardiac granuloma, or a rheumatoid granuloma.

[0235] In some embodiments, administration of the composition reduces a calcitriol level in the subject relative to a control.

[0236] In some embodiments, the calcitriol level is reduced by at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0237] In some embodiments, administration of the composition reduces a neopterin level in the subject relative to a control.

[0238] In some embodiments, the neopterin level is reduced by at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0239] In some embodiments, administration of the composition reduces a lysozyme level in the subject relative to a control.

[0240] In some embodiments, the lysozyme level is reduced by at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0241] In some embodiments, administration of the composition reduces a soluble IL-2R (slL-2R) level in the subject relative to a control.

[0242] In some embodiments, the slL-2R level is reduced by at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0243] In some embodiments, the subject has one or more of acute sarcoidosis, chronic sarcoidosis, progressive sarcoidosis, pulmonary sarcoidosis, remitting sarcoidosis, refractory sarcoidosis, advanced sarcoidosis, ocular sarcoidosis, cutaneous sarcoidosis, or neurosarcoidosis.

[0244] In some embodiments, the subject has received an anti-inflammatory medication.

[0245] In some embodiments, the subject is receiving an anti-inflammation medication.

[0246] In some embodiments, the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline, thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab.

[0247] In some embodiments, the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone.

[0248] In some embodiments, an outcome of the method is increased relative to the same method comprising use of a corticosteroid.

[0249] In some embodiments, the method comprises a reduction in a side effect compared to administration of a corticosteroid used at the same or at a lower dosage than the anti-TNFa antibody.

[0250] In some embodiments, the side effect is a steroid toxicity.BRIEF DESCRIPTION OF THE DRAWINGS

[0251] FIG. 1 illustrates a high-level overview of assessing XTMAB-16 in human subjects by using both a multiple ascending dose (MAD) study and a proof of concept (POC) study.

[0252] FIG. 2 illustrates a MAD study schematic for assessing XTMAB-16 in human subjects, kg: kilogram; mg: milligram; Q2W: every 2 weeks; Q4W: every four weeks.

[0253] FIG. 3 illustrates a POC study schematic for assessing XTMAB-16 in human subjects. Open circles represent a Q2W dosing schedule. Black closed circles represent a Q4W dosing schedule, kg: kilogram; mg: milligram; Q2W: every 2 weeks; Q4W: every four weeks; TBD: to be determined.

[0254] FIG. 4 illustrates a schematic for dose escalation in the MAD study of FIG.25. kg: kilogram; mg: milligram; Q2W: every 2 weeks; Q4W: every four weeks.

[0255] FIGS. 5A-5C illustrate granuloma formation in a human in vitro sarcoidosis model dosed with XTMAB-16 compared to prednisone in high responder subjects (FIG.5A), very high responder subjects (FIG. 5B) and low responder subjects (FIG. 5C) with sarcoidosis (n=15). Bars are mean (pg / mL) ±SD. Area Fraction (%): cumulative granuloma area as a percentage of the total image area; UNC: Uncoated beads; PPD: purified protein derivative; PRED: prednisone; *: p < 0.001 compared to UNC only group; f: P < 0.01 compared to UNC group; J: p < 0.001; §: p < 0.05 relative to PPD only group.

[0256] FIG. 6 illustrates percent change from baseline in prednisone or equivalent dose by visit in different XTMAB-16 treatment groups and placebo.

[0257] FIG. 7 illustrates mean change from baseline in Forced Vital Capacity percent (FVC%) by visit in different XTMAB-16 treatment groups and placebo.

[0258] FIG. 8 illustrates mean change from baseline in the King’s Sarcoidosis Questionnaire (KSQ) General Health Status Score (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0259] FIG. 9 illustrates mean change from baseline in KSQ Lung Score (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0260] FIG. 10 illustrates mean change from baseline in Steroid Toxicity Questionnaire (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0261] FIG. 11 illustrates mean change from baseline in Total Leicester Cough Questionnaire (LSQ) (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0262] FIG. 12 illustrates mean change from baseline in Patient Global Assessment (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0263] FIG. 13 illustrates mean change from baseline in Fatigue Assessment Scale Score (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0264] FIG. 14 illustrates mean change from baseline in Modified Medical Research Council Dyspnea Scale (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0265] FIG. 15 illustrates mean change from baseline in Six Minute Walk Distance (6MWD) (safety population) by visit in different XTMAB-16 treatment groups and placebo.

[0266] FIG. 16 illustrates a High-Resolution Computed Tomography (HRCT) Heat Map at week 12 in different XTMAB-16 treatment groups and placebo.

[0267] FIG. 17 illustrates serum concentration of XTMAB-16 by visit (safety population) in different XTMAB-16 treatment groups and placebo.DETAILED DESCRIPTION

[0268] While the present technology is capable of being embodied in various forms, the description below of several embodiments is made with the understanding that the present technology is to be considered as an exemplification of the present technology and is not intended to limit the present technology to the specific embodiments illustrated. Headings are provided for convenience only and are not to be construed to limit the present technology in any manner. Embodiments illustratedunder any heading may be combined with embodiments illustrated under any other heading.

[0269] The use of numerical values in the various quantitative values specified in this application, unless expressly indicated otherwise, are stated as approximations as though the minimum and maximum values within the stated ranges were both preceded by the word “about.” It is to be understood, although not always explicitly stated, that all numerical designations are preceded by the term “about.” It is to be understood that such range format is used for convenience and brevity and should be understood flexibly to include numerical values explicitly specified as limits of a range, but also to include all individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly specified. For example, a ratio in the range of about 1 to about 200 should be understood to include the explicitly recited limits of about 1 and about 200, but also to include individual ratios such as about 2, about 3, and about 4, and sub-ranges such as about 10 to about 50, about 20 to about 100, and so forth. It also is to be understood, although not always explicitly stated, that the reagents described herein are merely exemplary and that equivalents of such are known in the art. Furthermore, the term “about,” as used herein when referring to a measurable value such as an amount or concentration and the like, is meant to encompass variations of 20%, 10%, 5%, 1%, 0.5%, or even 0.1% of the specified amount.

[0270] The term “about” means a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by acceptable levels in the art. Typically, such variation may be as much 10% above and below a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length and such variation may be influenced by standard applicable measurement practices. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth.

[0271] Also, the ranges of the present technology are intended as a continuous range, including every value between the minimum and maximum values recited, as well as any ranges that may be formed by such values. The present technology comprises any and all (and ranges of any such ratios) that may be formed by dividing anumeric value of the present technology into any other numeric value of the present technology. Accordingly, the skilled person will appreciate that many such ratios, ranges, and ranges of ratios may be unambiguously derived from the numerical values presented herein and in all instances, such ratios, ranges, and ranges of ratios represent various embodiments of the present technology.

[0272] The terms “bind” and “binding” refer to all types of physical and chemical binding, reactions, complexing, attraction, chelating and the like.

[0273] “Amino acids” are molecules containing an amine group, a carboxylic acid group, and a side-chain that is specific to each amino acid. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen and have the generic formula H2N — CHR — COOH, wherein R represents a side chain group. The various a-amino acids differ in the side-chain moiety that is attached to the o-carbon. The “amino acids” of the present technology include the known naturally occurring protein amino acids, which are referred to by both their common three letter abbreviation and single letter abbreviation. See generally Synthetic Peptides: A User’s Guide, G. A. Grant, editor, W. H. Freeman & Co., New York (1992), the teachings of which are incorporated herein by reference, including the text and table set forth at pages 11 through 24. As set forth above, the term “amino acid” also includes stereoisomers and modifications of naturally occurring protein amino acids, non-protein amino acids, post-translationally modified amino acids, enzymatically synthesized amino acids, derivatized amino acids, constructs or structures designed to mimic amino acids, and the like. Modified and unusual amino acids are described generally in Synthetic Peptides: A User’s Guide, supra; Hruby et aL, Biochem.. 268:249-262 (1990); and Toniolo, Int. J. Peptide Protein Res. 35:287-300 (1990); the teachings of all of which are incorporated herein by reference.

[0274] “Antibody” refers to any form of antibody that exhibits the desired biological activity, such as inhibiting binding of a ligand to its receptor, or by inhibiting ligand-induced signaling of a receptor. Thus, “antibody” is used in the broadest sense and specifically covers, but is not limited to, monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, and multispecific antibodies (e.g., bispecific antibodies).

[0275] “Antibody fragment” and “antibody binding fragment” mean antigen-binding fragments and analogues of an antibody, typically including at least a portion of the antigen binding or variable regions (e.g., one or more CDRs) of the parental antibody. An antibody fragment retains at least some of the binding specificity of the parental antibody. Typically, an antibody fragment retains at least 10% of the parental binding activity when that activity is expressed on a molar basis. Preferably, an antibody fragment retains at least 20%, 50%, 70%, 80%, 90%, 95% or 100% or more of the parental antibody's binding affinity for the target. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules, e.g., sc-Fv, unibodies (technology from Genmab); nanobodies (technology from Domantis); domain antibodies (technology from Ablynx); and multispecific antibodies formed from antibody fragments. Engineered antibody variants are reviewed in Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0276] An “Fc” region contains two heavy chain fragments comprising the C H1 and C H2 domains of an antibody. The two heavy chain fragments are held together by two or more disulfide bonds and by hydrophobic interactions of the C H3 domains.

[0277] An antibody fragment, as used herein, may comprise a sufficient portion of the constant region to permit dimerization (or multimerization) of heavy chains that have reduced disulfide linkage capability, for example where at least one of the hinge cysteines normally involved in inter-heavy chain disulfide linkage is altered as described herein. In another embodiment, an antibody fragment, for example one that comprises the Fc region, retains at least one of the biological functions normally associated with the Fc region when present in an intact antibody, such as FcRn binding, antibody halflife modulation, Antibody Dependent Cell-Mediated Cytotoxicity (ADCC) function, and / or complement binding (for example, where the antibody has a glycosylation profile necessary for ADCC function or complement binding).

[0278] A “Fab fragment” is comprised of one light chain and the C H1 and variable regions of one heavy chain. The heavy chain of a Fab molecule cannot form a disulfide bond with another heavy chain molecule.

[0279] An “Fc” region contains two heavy chain fragments comprising the Cnl and C H2 domains of an antibody. The two heavy chain fragments are held together by two or more disulfide bonds and by hydrophobic interactions of the C H3 domains.

[0280] A Tab' fragment” contains one light chain and a portion of one heavy chain that contains the VH domain and the C H1 domain and also the region between the C H1 and CH2domains, such that an interchain disulfide bond can be formed between the two heavy chains of two Fab' fragments to form a F(ab')? molecule.

[0281] A “F(ab')2 fragment” contains two light chains and two heavy chains containing a portion of the constant region between the C H1 and CH2domains, such that an interchain disulfide bond is formed between the two heavy chains. A F(ab')2 fragment thus is composed of two Fab' fragments that are held together by a disulfide bond between the two heavy chains.

[0282] The “Fv region” comprises the variable regions from both the heavy and light chains, but lacks the constant regions.

[0283] A “single-chain Fv antibody” (or “scFv antibody”) refers to antibody fragments comprising the Vnand VL domains of an antibody, wherein these domains are present in a single polypeptide chain. Generally, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen binding. For a review of scFv, see Pluckthun (1994) THE PHARMACOLOGY OF MONOCLONAL ANTIBODIES, vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315. See also, International Patent Application Publication No. WO 88 / 01649 and U. S. Pat. Nos.4,946,778 and 5,260,203.

[0284] A “diabody” is a small antibody fragment with two antigen-binding sites. The fragments comprise a heavy chain variable domain (VH) connected to a light chain variable domain (VL) in the same polypeptide chain (Vn-VLor VL-VH). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, e.g., EP 404,097; WO 93 / 11161; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448.

[0285] A “domain antibody fragment” is an immunologically functional immunoglobulin fragment containing only the variable region of a heavy chain or the variable region of a light chain. In some instances, two or more VH regions are covalently joined with a peptide linker to create a bivalent domain antibody fragment. The two VH regions of a bivalent domain antibody fragment may target the same or different antigens.

[0286] The term “chimeric” antibody refers to antibodies in which a portion of the heavy and / or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (See, for example, U. S. Pat. No. 4,816,567 and Morrison et aL, 1984, Proc. Natl. Acad. Sci. USA 81:6851-6855).

[0287] “Humanized” forms of non-human (for example, murine) antibodies are chimeric antibodies that contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence. The humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature 321:522-525 (1986); Riechmann et aL, Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992).

[0288] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present technology may be made by the hybridoma method first described by Kohler et al., 1975, Nature 256:495, or may be made by recombinant DNA methods (see, for example, U. S. Pat. No. 4,816,567). The “monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al., 1991, Nature 352:624-628 and Marks et al., 1991, J. Mol. Biol. 222:581 -597, for example. The monoclonal antibodies herein specifically include “chimeric” antibodies.

[0289] As used herein, a sequence “variant” refers to a sequence that differs from the sequence of the present technology at one or more amino acid residues but which retains the biological activity of the resulting molecule.

[0290] As used herein, “% identity” between two sequences refers to a function of the number of identical positions shared by the sequences (i.e., % homology=# of identical positions / total # of positions×100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. For example, the percent identity between two amino acid sequences can be determined using the algorithm of E. Meyers and W. Miller (Comput. Appt. Biosci., 4:11-17 (1988)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (. Mol. Biol. 48:444-453 (1970)) algorithm which has beenincorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossom 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

[0291] “Specifically” binds, when referring to a ligand / receptor, antibody / antigen, or other binding pair, indicates a binding reaction which is determinative of the presence of the protein, e.g., TNFa, in a heterogeneous population of proteins and / or other biologies. Thus, under designated conditions, a specified ligand / antigen binds to a particular receptor / antibody and does not bind in a significant amount to other proteins present in the sample.

[0292] As used herein, a “pharmaceutically acceptable carrier” of a composition refers to a carrier or diluent that does not cause significant irritation to an organism, does not abrogate the biological activity and properties of the administered active ingredient, and / or does not interact in a deleterious manner with the other components of the composition in which it is contained. The term “carrier” encompasses any excipient, binder, diluent, filler, salt, buffer, solubilizer, lipid, stabilizer, or other material well known in the art for use in pharmaceutical formulations. The choice of a carrier for use in a composition will depend upon the intended route of administration for the composition. The preparation of pharmaceutically acceptable carriers and formulations containing these materials is described in, e.g., Remington's Pharmaceutical Sciences, 21st Edition, ed. University of the Sciences in Philadelphia, Lippincott, Williams & Wilkins, Philadelphia Pa., 2005, which is incorporated herein by reference in its entirety). Some examples of physiologically acceptable carriers include antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as TWEEN® (ICI, Inc.; Bridgewater, N. J.), polyethylene glycol (PEG), and PLURONICS™ (BASF; Florham Park, N. J.). An “excipient” of a composition refers to an inert substance added to a composition to further facilitate administration of a compound. Examples, without limitation, ofexcipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils, and polyethylene glycols.

[0293] As used herein, a “control” when referring to an antibody may refer to a composition lacking the anti-TNFa antibodies of the present technology or a composition having an antibody comprising different features from the anti-TNFa antibodies of the present technology. For example, the control may comprise an anti-TNFa antibody having a different amino acid sequence or a different post-translational modification status from the anti-TNFa antibodies of the present technology.

[0294] As used herein, a “control” when referring to a subject may refer to the subject at baseline (i.e., prior to administration of a composition of the present technology or another therapeutic intervention), a subject that does not have sarcoidosis and / or a granuloma, an untreated subject, a subject administered a placebo, or a subject administered a composition that is different from the composition that is administered to the treated subject, such as a corticosteroid.Anti-TNFa AntibodiesAmino Acid Sequences

[0295] The present technology provides compositions comprising an anti-TNFa antibody or an antigen binding fragment thereof. The anti-TNFa antibodies of the present technology specifically bind at least a portion of a TNFa protein or peptide. The TNFa protein or peptide may be produced by macrophages, monocytes, neutrophils, T cells, NK-cells, or fibroblasts, and may be membrane-bound or soluble. The anti-TNFa antibodies may bind a human or a nonhuman target. In some embodiments, the anti-TNFa antibodies of the present technology bind a protein listed in Table 1. In some embodiments, the anti-TNFa antibodies bind a protein comprising an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 1 or SEQ ID NO: 2. In some embodiments, the anti-TNFa antibodies bind a protein comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 1 or SEQ ID NO: 2. In some embodiments, the anti-TNFa antibodies bind a protein comprising an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 1 or SEQ ID NO: 2.Table 1: TNFa Proteins

[0296] The anti-TNFa antibodies may comprise a heavy chain comprising one or more amino acid sequences that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a sequence listed in Table 2. The anti-TNFa antibodies may comprise a heavy chain comprising one or more amino acid sequences that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a sequence listed in Table 2. The anti-TNFa antibodies may comprise a heavy chain comprising one or more amino acid sequences that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a sequence listed in Table 2.

[0297] The anti-TNFa antibodies of the present technology comprise a heavy chain having at least one Complementarity Determining Region (CDR) sequence. The at least one CDR sequence confers binding to a specific antigen (e.g., a TNFa peptide).

[0298] In some embodiments, the at least one CDR sequence comprises an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a CDR sequence listed in Table 2 (e.g., SEQ ID NO: 3, 4, 5, 6, 7, or 8). In some embodiments, the anti-TNFa antibodies comprise a heavy chain having a sequence that comprises CDR sequences about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, and 8. In some embodiments, the anti-TNFa antibodies comprise a heavy chain having a sequence that comprises CDR sequences at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, and 8. In some embodiments, the anti-TNFa antibodies comprise a heavy chain having a sequence that comprises CDR sequences at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, and 8. The CDR sequences may be distinct from other CDR sequences (e.g., do not overlap another CDR sequence) or at least a portion of a CDR sequence may overlap with a portion of another CDR sequence (e.g., two CDR sequences share at least a portion of the amino acid sequence).

[0299] In some embodiments, the anti-TNFa antibodies comprise a heavy chain comprising a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 3.

[0300] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 3.

[0301] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 3.

[0302] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 4.

[0303] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 4.

[0304] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 4.

[0305] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 5.

[0306] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 5.

[0307] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 5.

[0308] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 6.

[0309] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 6.

[0310] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 6.

[0311] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 7.

[0312] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 7.

[0313] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 7.

[0314] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 8.

[0315] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 8.

[0316] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 8.

[0317] In some embodiments, the anti-TNFa antibodies comprise a variable heavy (VH) domain having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 9.

[0318] In some embodiments, the anti-TNFa antibodies comprise a VH domain having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 9.

[0319] In some embodiments, the anti-TNFa antibodies comprise a VH having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 9.Table 2: Heavy Chain Anti-TNFa antibody Sequences

[0320] The anti-TNFa antibodies may comprise a light chain comprising one or more amino acid sequences that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a sequence listed in Table 3. The anti-TNFa antibodies may comprise a light chain comprising one or more amino acid sequences that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a sequence listed in Table 3. The anti-TNFa antibodies may comprise a light chain comprising one or more amino acid sequences that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a sequence listed in Table 3.

[0321] The anti-TNFa antibodies of the present technology comprise a light chain having at least one CDR sequence. The at least one CDR sequence confers binding to a specific antigen (e.g., a TNFa peptide).

[0322] In some embodiments, the at least one CDR sequence comprises an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a CDR sequence listed in Table 2 (e.g., SEQ ID NO: 10, 12, 13, 14, 15, or YA). In some embodiments, the at least one CDR sequence comprises an amino acid sequence thatis at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a CDR sequence listed in Table 2 (e.g., SEQ ID NO: 10, 12, 13, 14, 15, or YA). In some embodiments, the at least one CDR sequence comprises an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to a CDR sequence listed in Table 2 (e.g., SEQ ID NO: 10, 12, 13, 14, 15, or YA). In some embodiments, the anti-TNFa antibodies comprise a light chain having a sequence that comprises CDR sequences about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10, 12, 13, 14, 15, and YA. In some embodiments, the anti-TNFa antibodies comprise a light chain having a sequence that comprises CDR sequences at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10, 12, 13, 14, 15, and YA. In some embodiments, the anti-TNFa antibodies comprise a light chain having a sequence that comprises CDR sequences at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10, 12, 13, 14, 15, and YA. The CDR sequences may be distinct (e.g., do not overlap another CDR sequence) or may overlap (e.g., share at least a portion of an amino acid sequence).

[0323] In some embodiments, the anti-TNFa antibodies comprise a light chain comprising a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 10.

[0324] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 10.

[0325] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 10.

[0326] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to YA.

[0327] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: YA.

[0328] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: YA.

[0329] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 12.

[0330] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 12.

[0331] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 12.

[0332] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 13.

[0333] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 13.

[0334] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 13.

[0335] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 14.

[0336] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 14.

[0337] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 14.

[0338] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 15.

[0339] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 15.

[0340] In some embodiments, the anti-TNFa antibodies comprise a CDR having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 15.

[0341] In some embodiments, the anti-TNFa antibodies comprise a variable light (VL) domain having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 16.

[0342] In some embodiments, the anti-TNFa antibodies comprise a VL domain having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 16.

[0343] In some embodiments, the anti-TNFa antibodies comprise a VL having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 16.Table 3: Light Chain Anti-TNFa antibody SequencesAnti-TNFa Antibody Functions

[0344] Avidity of the anti-TNFa antibodies for the TNFa protein or peptide is determined by amino acid sequences on the heavy and / or light chain of each antibody. These amino acid sequences may comprise one or more CDRs. Binding of the anti-TNFa antibodies to the TNFa protein or peptide may reduce an activity of TNFa. For example, the anti-TNFa antibodies may reduce or prevent an outcome of TNFa signaling, including, but not limited to, upregulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) signaling, mitogen-activated protein kinase (MAPK) signaling, pro-apoptotic signaling, cytokine and / or chemokine production (e.g., Interleukin-1 (IL-1), Interleukin-6 (IL-6), lnterleukin-8 (IL-8), Interleukin-12 (IL-12), Interleukin-18 (IL-18), Tumor Necrosis Factor Beta (TNF-p), chemokine (C-X-C motif) ligands 1, 2, 5, 9, 10, and chemokine (C-C motif) ligands 2, 5, and 20)), upregulation of cell adhesion molecules (e.g., Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-Selectin, and P-Selectin), and reactive oxygen species (ROS) production (e.g., superoxide anions, hydrogen peroxide, and hydroxy radicals).

[0345] In some embodiments, binding of the anti-TNFa antibodies to the TNFa protein or peptide may reduce a concentration of TNFa in the plasma or other tissues of the subject. For example, the anti-TNFa antibodies may reduce membrane TNFa and / or cytoplasmic TNFa of resident, migrating, infiltrating, and / or intravascular cells (e.g., mononuclear, epithelial, endothelial, glomerular, myocyte, neural, or myoepithelial cells) in the bladder, cervix, esophagus, large intestine, liver (Kupffer cells), lymph node, lung, pancreas, placenta (Hofbauer cells), parathyroid, salivary gland, skin, small intestine, spleen, stomach, thyroid, thymus, tonsil, and uterus.Complement Dependent Cytotoxicity and Antibody Dependent Cell-Mediated Cytotoxicity:

[0346] The anti-TNFa antibodies may mediate Complement Dependent Cytotoxicity (CDC) and / or Antibody Dependent Cell-Mediated Cytotoxicity (ADCC) of mTNF-expressing cells. CDC or ADCC may be mediated through binding of the anti-TNFa antibodies to one or more of C1q, Fc receptors, FcyRI, FcyRllb, or FcRn. CDC may determine the ability of the anti-TNFa antibodies to induce cytotoxic effects on cells expressing TNFa in the presence of complement factors. ADCC may be mediated by NK cells as part of the humoral immune response. ADCC of the anti-TNFa antibodies may promote lysis of cells expressing TNFa proteins or peptides thereof in the presence of effector cells of the immune system such as NK cells, myocytes, macrophages, or eosinophil cells.

[0347] C1g Binding: C1q, the first subcomponent of the C1 complex of the classical pathway of complement activation, is thought to bind to sites on the CH2 domain of IgG. C1q comprises the C1qA (Accession: NP 057075.1), C1qB (Isoform 1 Accession: NP 000482.3; Isoform 2 Accession: NP 001365085.1), and C1qC (Isoform 1 Accession: NP 758957.2; Isoform 2 Accession: NP 001334549.1) peptide chains. Together with 2 serine proteases, C1 r (Isoform 1 Accession: NP 001724.4; Isoform 2 Accession: NP 001341275.1) and C1 s (Isoform 1 Accession: NP 001725.1; Isoform 2 Accession: NP_001333779.1), 01 q forms the complex 01, the first component of the complement. Activation of the complement cascade system generates 03 and 05 convertase enzymes. These enzymes generate the pro-inflammatory 03a and 05a anaphylatoxins and catalyze formation of the pore-like membrane attack complex (05-9) that may insert into cell membranes causing damage by lytic or sublytic mechanisms.

[0348] In some embodiments, the Fc portion of the anti-TNFo antibodies or the antigen binding fragment thereof comprising the Fc portion may bind 01 q or at least a portion of C1q (e.g., C1qA, C1qB, C1qC, or peptides thereof). In some embodiments, binding occurs at the CH2 domain of the anti-TNFa antibodies. Binding to 01 q or at least the portion of 01 q may block 01 q function and / or signaling. Nonlimiting examples of 01 q signaling include activation of the complement cascade system.

[0349] Fc Receptor Binding: CDC and / or ADCC may occur through binding of the anti-TNFa antibodies to Fc receptors (e.g., Fey Rl, RII, and Rill), also known as CD64 (GenBank: AAI52384.1), CD32 (GenBank: AAI48274.1), and CD16 (NCBI: NP 001373379.1), respectively. In some embodiments, the Fc portion of the anti-TNFaantibodies or the antigen binding fragment thereof comprising the Fc portion may bind a Fc receptor or at least a portion of an Fc receptor (e.g., Fey Rl, RII, and Rill, or peptides thereof). Binding to Fc receptors or at least the portion of the Fc receptor may trigger ADCC and cytotoxic cell activation and may lead to destruction of the cells expressing TNFa.

[0350] FcyRI Binding: FcyRI (also known as CD64 (GenBank: AAI52384.1)) is a 72 kDa glycoprotein, expressed on mononuclear phagocytes, and may binds IgG via the Fc binding domain. FcyRI exhibits high affinity for IgG, Ka = 108-109 M-1 and may bind monomeric IgG. FcyRI that is released to biological fluids may function as an immunoglobulin binding factor. FcyRI expression may be induced by interferon (IFN)-gamma and may play a role in ADCC and clearance of immune complexes. FcyRI binding may also be implicated in the pathogenesis of immune complexes and autoantibody mediated diseases. In some embodiments, the Fc portion of the anti-TNFa antibodies or the antigen binding fragment thereof comprising the Fc portion may bind FcyRI or at least a portion of FcyRI. Binding to FcyRI may trigger ADCC and cytotoxic cell activation and may lead to destruction of the cells expressing TNFa.

[0351] FcRn Binding: FcRn (Accession: AAF72596.1) is composed of 2 subunits (a subunit and p2 microglobulin). The a subunit is structurally related to major histocompatibility complex (MHC) class I proteins and may also associate with p2 microglobulin. Binding of IgG to FcRn, which is pH dependent, protects the antibody from degradation via an endocytosis salvage pathway, thereby prolonging the half-life of the IgG in the serum.

[0352] In some embodiments, the anti-TNFa antibodies or the antigen binding fragment thereof may bind FcRn at least a portion of FcRn (e.g., a subunit, p2 microglobulin, or a peptide thereof). Binding to FcRn may trigger protect the anti-TNFa antibodies from degradation and / or prolong the anti-TNFa antibodies half-life.

[0353] FcvRIlb Binding: Binding of anti-TNFa antibodies to FcyRllb (isoform 1 Accession: NP 001381406.1) may modulate immune responses such as ADCC. FcyRllb shows weak affinity for monomeric IgG, Ka < 107 M-1, and may only interact effectively with multimeric immune complexes. In some embodiments, the anti-TNFa antibodies or the antigen binding fragment thereof may bind FcyRllb or at least a portionof FcyRllb. Binding to FcyRllb may trigger ADCC and cytotoxic cell activation and may lead to destruction of the cells expressing TNFa.Post- Translational Modifications

[0354] The anti-TNFa antibodies of the present technology may comprise post-translational modifications (e.g., glycosylation, N-terminal glutaminyl cyclization, C-terminal lysine clipping, sialylation, methylation, acetylation, ubiquitination, sumoylation, phosphorylation, proteolytic cleavage) that may influence features of the antibody (e.g., immunogenicity, stability, avidity, dissociation rates). For example, the anti-TNFa antibodies may be sialylated with one of more N-acetylneuraminic acid (Neu5Ac) molecules and / or may lack N-glycolylneuraminic acid (Neu5Gc). Neu5Ac is the predominant sialic acid found in human cells, whereas the main sialic acid form of other TNF inhibitors is Neu5Gc, which is only found in non-human cells and may be immunogenic. In some embodiments, the anti-TNFa antibody comprises an as paragine-l inked glycosylation site within a constant Fc region on at least one of the heavy chains. In some embodiments, the anti-TNFa antibody comprises an as paragine-l inked glycosylation site within the constant Fc region on both of the heavy chains.

[0355] In some embodiments, the anti-TNFa antibodies are sialylated at Asn 297. In some embodiments, Asn 297 is sialylated with Neu5Ac.

[0356] In some embodiments, the anti-TNFa antibodies of the present technology are glycosylated. In some embodiments, the anti-TNFa antibodies are glycosylated at an asparagine residue (e.g., Asn 300) on at least one of the heavy chains. In some embodiments, the anti-TNFa antibodies are glycosylated at an asparagine residue (e.g., Asn 300) on both of the heavy chains.

[0357] In some embodiments, the anti-TNFa antibodies of the present technology are fucosylated.

[0358] In some embodiments, the anti-TNFa antibodies of the present technology comprise one or more disulfide bonds (e.g., intra-chain or inter-chain). In some embodiments, the one or more disulfide bonds enhance the stability and / or structural integrity of the antibody relative to an antibody lacking disulfide bonds. In someembodiments, the anti-TNFa antibodies comprise 16 disulfide bonds (12 intra-chain and 4 inter-chain).

[0359] In some embodiments, the anti-TNFa antibodies of the present technology comprise a C-terminal lysine on at least one of the heavy chains. In some embodiments, the anti-TNFa antibodies of the present technology comprise a C-terminal lysine on both of the heavy chains. In some embodiments, the C-terminal lysine is not clipped. In some embodiments, the charge of the anti-TNFa antibodies may be modified by C-terminal lysine clipping on one or both of the heavy chains.

[0360] In some embodiments, the anti-TNFa antibodies may be generated using a biological system which influences the types of post translational modifications made to the anti-TNFa antibodies. For example, the anti-TNFa antibodies may be generated using a Chinese hamster ovary (CHO) cell line rather than a cell line that is used in the production of other TNFa inhibitors (e.g., SP2 cell line). Nonlimiting examples of cell lines which may be used to generate the anti-TNFa antibodies include CHO cells, NSO cells, hybridoma cells, SP2 / 0 cells, human embryonic kidney (HEK) cells, PER. C6 cells, yeast cells, and myeloma cells.Pharmacodynamics and Pharmacokinetics

[0361] The anti-TNFa antibodies of the present technology may comprise features that modify pharmacodynamic parameters (e.g., binding, efficacy, and or potency) and / or pharmacokinetic parameters (e.g., absorption, distribution, metabolism, or elimination) relative to a control (e.g., an anti-TNFa antibody comprising a different sequence and / or a different post translational modification status from the anti-TNFa antibodies of the present technology). Features such as the amino acid sequences or the post translational modifications of the anti-TNFa antibodies may contribute to the pharmacodynamic or pharmacokinetic differences relative to the control.

[0362] In some embodiments, the anti-TNFa antibodies of the present technology have an increased affinity for a TNFa protein or peptide thereof, relative to a control. In some embodiments, the anti-TNFa antibodies of the present technology comprise an increased affinity for C1q, Fc receptors, FcyRI, FcyRllb, or FcRn proteins or peptides thereof.

[0363] The affinity may be assessed as a dissociation constant (KD) value. In some embodiments, the anti-TNFa antibodies of the present technology comprise a reduced KD from a TNFa protein or peptide thereof, relative to a control. In some embodiments, the anti-TNFa antibodies of the present technology comprise a reduced KD from C1q, Fc receptors, FcyRI, FcyRllb, or FcRn proteins or peptides thereof.

[0364] In some embodiments, the reduction in KD is a reduction by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 99% relative to the control.

[0365] In some embodiments, the reduction in KD is a reduction by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 99% relative to the control.

[0366] In some embodiments, the reduction in KD is a reduction by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 99% relative to the control.

[0367] In some embodiments, the anti-TNFa antibodies of the present technology comprise an increased half-life relative to a control. The control may comprise an anti-TNFa antibody or other TNFa inhibitor that lacks a post-translational modification possessed by the anti-TNFa antibodies of the present technology.

[0368] In some embodiments, the increase in half-life is an increase by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0369] In some embodiments, the increase in half-life is an increase by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0370] In some embodiments, the increase in half-life is an increase by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0371] In some embodiments, the anti-TNFa antibodies of the present technology comprise a reduced clearance (CL) relative to a control. The control may comprise an anti-TNFa antibody or other TNFa inhibitor that lacks a post-translational modification possessed by the anti-TNFa antibodies of the present technology. “Clearance” may refer to the elimination, absorption, and / or metabolism of the anti-TNFa antibodies inthe subject’s plasma. Clearance may be assessed as volume of plasma cleared of the anti-TNFa antibodies over time (e.g., mL / min, L / hr, or L / day) and / or may be normalized to body weight of the subject (e.g., mL / min / kg). Reduced clearance may also be represented by an increase in half-life or volume of distribution (Vd). In some embodiments, measuring clearance comprises measuring a terminal elimination rate constant (Az) or an inter-compartmental clearance (Q).

[0372] In some embodiments, the reduction in clearance comprises a measurement about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0373] In some embodiments, the reduction in clearance comprises a measurement at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0374] In some embodiments, the reduction in clearance comprises a measurement at least about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0375] In some embodiments, the reduction in clearance comprises a measurement during administration of the anti-TNFa antibodies.

[0376] In some embodiments, the reduction in clearance comprises a measurement at the completion of administration of the anti-TNFa antibodies.

[0377] In some embodiments, the reduction in clearance is a reduction by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0378] In some embodiments, the reduction in clearance is a reduction by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 100% relative to the control.

[0379] In some embodiments, the reduction in clearance is a reduction by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0380] In some embodiments, the anti-TNFa antibodies of the present technology comprise an increased tissue, plasma, and / or serum concentration relative to a control. The control may be an anti-TNFa antibody or other TNFa inhibitor that lacks a post-translational modification possessed by the anti-TNFa antibodies of the present technology. “Concentration” may comprise a measurement reflecting one or more of the absolute amounts of the anti-TNFa antibodies, the absorption of the anti-TNFa antibodies, the metabolism of anti-TNFa antibodies, or the elimination of anti-TNFa antibodies.

[0381] The increased tissue, plasma, and / or serum concentration may be an increase in concentration of the anti-TNFa antibodies at a given time point relative to a control administered at the same dose and measured at the same time point. The concentration may be measured at an intermediate time point or a final time point and may be measured as a mean residence time (MRT), an average concentration (Cavg), a trough concentration (Ctrough), or a concentration at the end of administration (e.g., infusion) time (CT).

[0382] In some embodiments, the increased concentration is reflected by an increase in peak plasma concentration (Cmax). An increase in Cmax may suggest increased absorption, reduced metabolism, or slower elimination of the anti-TNFa antibodies, relative to a control. In some embodiments, Cmax comprises a dose normalized Cmax (DNC max).

[0383] In some embodiments, the increased concentration is reflected by a reduction in time to reach Cmax (Tmax). A reduced Tmax may suggest increased absorption, reduced metabolism, or slower elimination of the anti-TNFa antibodies, relative to a control.

[0384] In some embodiments, the increased concentration is reflected by an increase in area under the curve (AUC) An increase in AUC may signify increased exposure to the anti-TNFa antibodies and / or may suggest increased absorption, reduced metabolism, or slower elimination of the anti-TNFa antibodies, relative to a control. The AUC measurement may comprise an Area Under the Curve for Concentration of Drug in Non-Compartmental Analysis (DNAUC).

[0385] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement about 10 minutes, 20 minutes, 30 minutes, 40minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0386] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0387] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement at least about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0388] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement during administration of the anti-TNFa antibodies.

[0389] In some embodiments, the increase in tissue, plasma, and / or serum concentration comprises a measurement at the completion of administration of the anti-TNFa antibodies.

[0390] In some embodiments, the increase in tissue, plasma, and / or serum concentration is an increase by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0391] In some embodiments, the increase in tissue, plasma, and / or serum concentration is an increase by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0392] In some embodiments, the increase in tissue, plasma, and / or serum concentration is an increase by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0393] In some embodiments, the anti-TNFa antibodies of the present technology comprise an increased distribution relative to a control. The control may be an anti-TNFa antibody or other TNFa inhibitor that lacks a post-translational modification possessed by the anti-TNFa antibodies of the present technology.

[0394] The increased distribution may be an increase in distribution of the anti-TNFa antibodies at a given time point relative to a control administered at the same dose and measured at the same time point. The distribution may be measured at an intermediate time point or a final time point.

[0395] In some embodiments, the measurement of distribution comprises measuring a volume of distribution at the terminal phase (Vd or Vais), a central volume of distribution (V), a peripheral volume of distribution (V2), an apparent volume of distribution (Vz), or a measurement of distribution comprises measuring a volume of distribution at steady state (Vss). A high or increased Vd, VdB, Vz, and / or Vss may suggest large distribution beyond the tissue, plasma, and / or serum compartment, relative to the control. In some embodiments, the measurement of distribution is a lung tissue drug distribution. The lung tissue distribution of the anti-TNFa antibodies may be reflected by a reduction in central drug volumes or V or an increase in distributional clearance (Clp) or linear clearance (Cl) (e.g., from a serum, blood, or plasma measurement) and an increase in lung tissue volume (e.g., a V2 of lung tissue) by an increase in peripheral volumes of distribution of anti-TNFa antibodies (e.g., a Vz or Vssof lung tissue).

[0396] In some embodiments, the increase in distribution comprises a measurement about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0397] In some embodiments, the increase in distribution comprises a measurement at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0398] In some embodiments, the increase in distribution comprises a measurement at least about 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day,2 days, 3 days, 4 days, 5 day, 6 days, or 1 week after administration of the anti-TNFa antibodies.

[0399] In some embodiments, the increase in distribution comprises a measurement during administration of the anti-TNFa antibodies.

[0400] In some embodiments, the increase in distribution comprises a measurement at the completion of administration of the anti-TNFa antibodies.

[0401] In some embodiments, the increase in distribution is an increase in anti-TNFa antibody distribution in a lung tissue measurement.

[0402] In some embodiments, the increase in distribution is an increase by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0403] In some embodiments, the increase in distribution is an increase by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0404] In some embodiments, the increase in distribution is an increase by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0405] In some embodiments, the anti-TNFa antibodies of the present technology comprise an increased no observed effect level (NOEL) relative to a control. The increased NOEL may indicate that the anti-TNFa antibodies are less toxic or have a wider safety margin relative to the control.

[0406] In some embodiments, the increase in NOEL is an increase by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0407] In some embodiments, the increase in NOEL is an increase by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0408] In some embodiments, the increase in NOEL is an increase by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0409] In some embodiments, the anti-TNFa antibodies of the present technology comprise an increased severe toxic dose (STD) level or highest non-severely toxic dose (HNSTD) relative to a control. The increased STD level may indicate that the anti-TNFa antibodies are less toxic relative to the control administered at the same dose. In some embodiments, the increased STD level may indicate that a higher dose of anti-TNFa antibodies is required to observe a severe toxic effect, relative to the control. The increased HNSTD level may indicate that there is a greater difference between an effective dose of the anti-TNFa antibodies and a dose of the anti-TNFa antibodies that causes severe toxicity, relative to those of the control.

[0410] In some embodiments, the increase in STD level or HNSTD level is an increase by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0411] In some embodiments, the increase in STD level or HNSTD level is an increase by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0412] In some embodiments, the increase in STD level or HNSTD level is an increase by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0413] In some embodiments, the anti-TNFa antibodies of the present technology comprise an increase in TNFa inhibition, relative to a control. The increase in TNFa inhibition may be reflected by a reduced half-maximal inhibitory concentration (IC50), a a reduced ninety percent inhibitory concentration (IC90), a reduced half-maximal effective concentration (EC50), or a reduced ninety percent maximal effective concentration (EC90) with respect to TNFa activity or function, relative to a control. The reduced IC50 or IC90 may indicate that a lower dose or molar amount of anti-TNFaantibodies is required to inhibit TNFa activity and / or function by 50% or 90%, respectively, relative to that of a control. The reduced EC50 or EC90 may indicate that a lower dose or molar amount of the anti-TNFa antibodies are required to achieve 50% or 90%, respectively, of a desired effect, relative to that of a control.

[0414] In some embodiments, the increase TNFa inhibition is an increase by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0415] In some embodiments, the increase in TNFa inhibition is an increase by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0416] In some embodiments, the increase in TNFa inhibition is an increase by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, or 1000% relative to the control.

[0417] In some embodiments, the reduction in IC50, IC90, EC50, or EC90 is a reduction by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0418] In some embodiments, the reduction in IC50, IC90, EC50, or EC90 is a reduction by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0419] In some embodiments, the reduction in IC50, IC90, EC50, or EC90 is a reduction by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0420] In some embodiments, the anti-TNFa antibodies of the present technology comprise a reduced dissociation constant (Kd) or receptor occupancy (RO) value for TNFa, relative to a control. The reduced Kd or RO value may indicate that the anti-TNFa antibodies have a higher affinity for at least a portion of TNFa. The reduced Kd or RO value may indicate that the anti-TNFa antibodies are more effective than a control administered at the same dose. The reduced RO value may indication that the anti-TNFa antibodies are more potent than controls at a low TNFa engagement level. In some embodiments, the RO value may be reflected by a receptor occupancy 10% (RO10) or a receptor occupancy RO20 value, which may indicate a concentration of the anti-TNFa antibodies required to occupy 10% or 20% of the available TNFa targets, respectively.

[0421] In some embodiments, the reduction in the Kd or RO value is a reduction by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0422] In some embodiments, the reduction in the Kd or RO value is a reduction by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

[0423] In some embodiments, the reduction in the Kd or RO value is a reduction by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.Signal Peptides

[0424] The anti-TNFa antibodies of the present technology may comprise one or more signal peptides. The signal peptides may be present in precursor and / or mature forms of the anti-TNFa antibodies and may direct peptides of the anti-TNFa antibodies to specific cellular locations. Nonlimiting examples of signal peptides include signal peptides that direct peptides to organelles (e.g., endoplasmic reticulum), signal peptides that promote peptide secretion, signal peptides that regulate protein sorting to subcellular components, signal peptides that promote peptide translocation across membranes, and signal peptides that promote peptide insertion into membranes. In some embodiments, the signal peptide is cleaved.

[0425] In some embodiments, the signal peptides comprise SEQ ID NO: 17 or SEQ ID NO: 18, listed in Table 4.

[0426] In some embodiments, the anti-TNFa antibodies comprise a signal peptide having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 17.

[0427] In some embodiments, the anti-TNFa antibodies comprise a signal peptide having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 17.

[0428] In some embodiments, the anti-TNFa antibodies comprise a signal peptide having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 17.

[0429] In some embodiments, the anti-TNFa antibodies comprise a signal peptide having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 18.

[0430] In some embodiments, the anti-TNFa antibodies comprise a signal peptide having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 18.

[0431] In some embodiments, the anti-TNFa antibodies comprise a signal peptide having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 18.

[0432] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 19.

[0433] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 19.

[0434] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 19.

[0435] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain having an amino acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 20.

[0436] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain having an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 20.

[0437] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain having an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 20.Table 4: Signal PeptidesNucleic Acid Sequences

[0438] In some embodiments, the anti-TNFa antibodies comprise a signal peptide encoded by a nucleic acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 21.

[0439] In some embodiments, the anti-TNFa antibodies comprise a signal peptide encoded by a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 21.

[0440] In some embodiments, the anti-TNFa antibodies comprise a signal peptide encoded by a nucleic acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 21.

[0441] In some embodiments, the anti-TNFa antibodies comprise a signal peptide encoded by a nucleic acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 22.

[0442] In some embodiments, the anti-TNFa antibodies comprise a signal peptide encoded by a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 22.

[0443] In some embodiments, the anti-TNFa antibodies comprise a signal peptide encoded by a nucleic acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 22.

[0444] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain encoded by a nucleic acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 23.

[0445] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain encoded by a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 23.

[0446] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain encoded by a nucleic acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 23.

[0447] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain encoded by a nucleic acid sequence that is about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 24.

[0448] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain encoded by a nucleic acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 24.

[0449] In some embodiments, the anti-TNFa antibodies comprise a signal peptide on a peptide chain encoded by a nucleic acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 99%, or 100% Identical to SEQ. ID NO: 24.Table 5: Nucleic Acid SequencesOther Anti-TNFa Antibody Features

[0450] The anti-TNFa antibodies of the present technology may comprise an isotype that influences functional properties and / or structural features of the antibody. In some embodiments the anti-TNFa antibodies comprise an isotype selected from the group consisting of IgG, IgM, IgA, IgD, and IgE. The light chain may comprise isotype Kor isotype A. In some embodiments, the anti-TNFa antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG 1 antibody. In some embodiments, the IgG 1 antibody comprises a kappa isotype.

[0451] In some embodiments, the anti-TNFa antibodies of the present technology are chimeric antibodies. Nonlimiting examples of chimeric antibodies include humanmurine antibodies, human-rat antibodies, human-hamster antibodies, human-rabbit antibodies, human-bovine antibodies, and human-goat antibodies. In some embodiments, the chimeric antibodies comprise a humanized antibody.Compositions and Formulations

[0452] One or more anti-TNFa antibodies of the present technology may be present in a composition (e.g., a pharmaceutical composition). In some embodiments, the composition comprises a pharmaceutically acceptable carrier and / or excipient. The pharmaceutically acceptable carrier and / or excipient may comprise aqueous or nonaqueous carriers that may facilitate dissolution of the anti-TNFa antibodies. Nonlimiting examples of pharmaceutically acceptable carriers and / or excipients include sucrose, polysorbate 80, monobasic sodium phosphate, monohydrate, dibasic sodium phosphate, dihydrate. The composition may comprise a filler or diluent (e.g., lactose, mannitol, and microcrystalline cellulose), a disintegrant (e.g., croscarmellose sodium, crospovidone, starches), a buffer (e.g., phosphate buffer or acetate buffers), or a solvent (e.g., water, alcohol, glycerin).

[0453] In some embodiments, the composition does not comprise a preservative.

[0454] In some embodiments, the composition is sterilized (e.g., sterilization by filtration).

[0455] In some embodiments, the compositions comprise one or more anti-TNFa antibodies of the present technology in an amount of about 0.1% w / v or w / w of the composition, at least about 1% w / v or w / w of the composition; about 10% w / v or w / w of the composition; about 20% w / v or w / w of the composition; about 30% w / v or w / w of the composition; about 40% w / v or w / w of the composition; about 50% w / v or w / w of the composition; about 60% w / v or w / w of the composition; about 70% w / v or w / w of the composition; about 80% w / v or w / w of the composition; about 90% w / v or w / w of thecomposition; about 95% w / v or w / w of the composition; or about 99% w / v or w / w of the composition.

[0456] In some embodiments, the compositions comprise one or more anti-TNFa antibodies of the present technology in an amount of at least 0.1% w / v or w / w of the composition, at least 1% w / v or w / w of the composition; at least 10% w / v or w / w of the composition; at least 20% w / v or w / w of the composition; at least 30% w / v or w / w of the composition; at least 40% w / v or w / w of the composition; at least 50% w / v or w / w of the composition; at least 60% w / v or w / w of the composition; at least 70% w / v or w / w of the composition; at least 80% w / v or w / w of the composition; at least 90% w / v or w / w of the composition; at least 95% w / v or w / w of the composition; or at least 99% w / v or w / w of the composition.

[0457] In some embodiments, the compositions comprise one or more anti-TNFa antibodies of the present technology in an amount of at least about 0.1% w / v or w / w of the composition, at least about 1% w / v or w / w of the composition; at least about 10% w / v or w / w of the composition; at least about 20% w / v or w / w of the composition; at least about 30% w / v or w / w of the composition; at least about 40% w / v or w / w of the composition; at least about 50% w / v or w / w of the composition; at least about 60% w / v or w / w of the composition; at least about 70% w / v or w / w of the composition; at least about 80% w / v or w / w of the composition; at least about 90% w / v or w / w of the composition; at least about 95% w / v or w / w of the composition; or at least about 99% w / v or w / w of the composition.

[0458] In some embodiments, the composition comprises a lyophilized drug product (lyophilized powder or lyophilized cake of the anti-TNFa antibody). In some embodiments, the lyophilized drug product is reconstituted (e.g., using water or saline) prior to administration.

[0459] In some embodiments, the reconstituted composition provides a solution having a pH of about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8.0.

[0460] In some embodiments, the reconstituted composition provides a solution having a pH of at least 5.0, at least 5.1, at least 5.2, at least 5.3, at least 5.4, at least5.5, at least 5.6, at least 5.7, at least 5.8, at least 5.9, at least 6.0, at least 6.1, at least 6.2, at least 6.3, at least 6.4, at least 6.5, at least 6.7, at least 6.8, at least 6.9, at least 7.0, at least 7.1, at least 7.2, at least 7.3, at least 7.4, at least 7.5, at least 7.6, at least 7.7, at least 7.8, at least 7.9, or at least 8.0.

[0461] In some embodiments, the reconstituted composition provides a solution having a pH of at least about 5.0, at least about 5.1, at least about 5.2, at least about 5.3, at least about 5.4, at least about 5.5, at least about 5.6, at least about 5.7, at least about 5.8, at least about 5.9, at least about 6.0, at least about 6.1, at least about 6.2, at least about 6.3, at least about 6.4, at least about 6.5, at least about 6.7, at least about 6.8, at least about 6.9, at least about 7.0, at least about 7.1, at least about 7.2, at least about 7.3, at least about 7.4, at least about 7.5, at least about 7.6, at least about 7.7, at least about 7.8, at least about 7.9, or at least about 8.0.

[0462] In some embodiments, the reconstituted composition provides a solution having a concentration of an anti-TNFu antibody that is about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, about 10 mg / mL, about 11 mg / mL, about 12 mg / mL about 13 mg / mL, about 14 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / ML, about 30 mg / mL, or about 40 mg / mL, about 50 mg / mL, about 60 mg / mL, about 70 mg / mL, about 80 mg / mL, about 90 mg / mL, or about 100 mg / mL.

[0463] In some embodiments, the reconstituted composition provides a solution having a concentration of an anti-TNFa antibody that is at least 0.2 mg / mL, 0.5 mg / mL, 1 mg / mL, at least 2 mg / mL, at least 3 mg / mL, at least 4 mg / mL, at least 5 mg / mL, at least 6 mg / mL, at least 7 mg / mL, at least 8 mg / mL, at least 9 mg / mL, at least 10 mg / mL, at least 11 mg / mL, at least 12 mg / mL at least 13 mg / mL, at least 14 mg / mL, at least 15 mg / mL, at least 20 mg / mL, at least 25 mg / ML, at least 30 mg / mL, or at least 40 mg / mL, at least 50 mg / mL, at least 60 mg / mL, at least 70 mg / mL, at least 80 mg / mL, at least 90 mg / mL, or at least 100 mg / mL.

[0464] In some embodiments, the reconstituted composition provides a solution having a concentration of an anti-TNFa antibody that is at least about 0.2 mg / mL, 0.5 mg / mL, 1 mg / mL, at least about 2 mg / mL, at least about 3 mg / mL, at least about 4 mg / mL, at least about 5 mg / mL, at least about 6 mg / mL, at least about 7 mg / mL, at least about 8 mg / mL, at least about 9 mg / mL, at least about 10 mg / mL, at least about 11mg / mL, at least about 12 mg / mL at least about 13 mg / mL, at least about 14 mg / mL, at least about 15 mg / mL, at least about 20 mg / mL, at least about 25 mg / ML, at least about 30 mg / mL, or at least about 40 mg / mL, at least about 50 mg / mL, at least about 60 mg / mL, at least about 70 mg / mL, at least about 80 mg / mL, at least about 90 mg / mL, or at least about 100 mg / mL.

[0465] In some embodiments, the composition or the solution is diluted for administration. Nonlimiting examples of diluents include sodium chloride, water (e.g., sterile water for injection (SWFI)), dextrose solutions, bacteriostatic solutions, or Ringer’s solutions (e.g., solutions comprising electrolytes, lactated Ringer’s solution).

[0466] The compositions may be formulated for intraperitoneal, intravenous, parenteral, subcutaneous, intramuscular, intracerebroventricular, or oral administration. In some embodiments, the compositions formulated for parenteral administration comprise the composition in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. The term “parenteral”, as used herein, includes subcutaneous, intravenous, intraperitoneal, intramuscular, and intralesional, or infusion techniquesAssociated Methods

[0467] The present technology provides methods comprising administering one or more compositions of the present technology to a subject in need thereof. In some embodiments, the present technology comprises methods of treating or reducing sarcoidosis in a subject in need thereof relative to a control. In some embodiments, the present technology comprises methods of reducing or tapering corticosteroid use in a subject with sarcoidosis relative to a control. In some embodiments, the present technology comprises methods of reducing granuloma size or granuloma formation in a subject in need thereof relative to a control. The methods may comprise reducing, preventing, or otherwise ameliorating a granuloma inflammation level, relative to a control. A granuloma inflammation comprises the onset, increase in, and / or persistence of inflammation due to the presence of a granuloma. Nonlimiting examples of granuloma inflammation include a chronic immune response, a proinflammatory cytokine or chemokine production, and a tissue damage, such as an organ scarring. The compositions of the present technology may reduce, prevent, or otherwise ameliorate the granuloma inflammation level by preventing or reducing a T cell response or a Thelper cell response (e.g., Th1 ), relative to the control. The T cell response or the T helper cell response may comprise the promotion or increase in pro-inflammatory cytokine signaling and / or expression level. Nonlimiting examples of pro-inflammatory cytokines include interleukin 1 (IL-1), interleukin 2 (IL-2), TNF-o, and interferon gamma (IFN-y). In some embodiments, the control comprises the subject at baseline, the subject at an intermediate timepoint, a second subject not receiving treatment, a second subject at an intermediate time point, a subject receiving a composition that is different from the compositions of the present technology (e.g., a corticosteroid), or a second subject at baseline.Subjects

[0468] The subject of the present technology may be a male or a female subject. In some embodiments, the subject is about 18 to about 80 years of age. In some embodiments, the subject is about 25 to about 75 years of age. The subject may be white or non-Hispanic or Latino.

[0469] In some embodiments, the subject has a weight of about 50 kg to about 140 kg.

[0470] In some embodiments, the subject has a weight of about 45 kg to about 160 kg.

[0471] In some embodiments, the subject has a systolic blood pressure of about 90 mmhg to about 140 mmhg. In some embodiments, the subject has a diastolic blood pressure of about 60 mmhg to about 90 mmhg. In some embodiments, the subject has a resting pulse of about 50 beats / min to about 110 beats / min.

[0472] In some embodiments, the subject has one or more of acute sarcoidosis, chronic sarcoidosis, progressive sarcoidosis, pulmonary sarcoidosis (e.g., with or without extrapulmonary manifestations), remitting sarcoidosis, refractory sarcoidosis, advanced sarcoidosis, ocular sarcoidosis, cutaneous sarcoidosis, or neurosacoidosis. In some embodiments, the sarcoidosis comprises high responder or low responder sarcoidosis, wherein the designation of high or low responder sarcoidosis may indicate the response to a therapeutic intervention or a response to purified protein derivative (PPD)-coated beads in terms of in vitro granuloma formation.

[0473] In some embodiments, the subject has one or more granulomas. In some embodiments, the one or more granulomas comprises a skin granuloma, a lung granuloma, a lymph node granuloma, an ocular granuloma, a liver granuloma, a spleen granuloma, a cardiac granuloma, a rheumatoid granuloma, a nervous system granuloma, or a bone and / or joint granuloma.

[0474] In some embodiments, the subject has a Modified Medical Research Conference (mMRC) Dyspnea Scale of > 1.

[0475] In some embodiments, the subject has a Scadding CXR grade determined by based on chest X-ray methods. In some embodiments, the subject has a Scadding CXR grade selected from the group consisting of Stage 0, Stage II, Stage III, or Stage IV.

[0476] In some embodiments, the subject is at least 18 years of age. In some embodiments, the subject is between about 18 and about 80 years of age. In some embodiments, the subject weighs at least 45 kg. In some embodiments, the subject weights between about 45 and about 160 kg.

[0477] In some embodiment, the subject has sarcoidosis and / or one or more granulomas and one or more additional inflammatory conditions. In some embodiments, the inflammatory condition is an autoimmune disorder. Nonlimiting examples of autoimmune disorders include Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), Type 1 Diabetes (T 1 D), psoriasis, celiac disease, Hashimoto's thyroiditis, Graves' disease, Crohn's disease, and Myasthenia Gravis (MG).

[0478] In some embodiments, the subject comprises anti-drug antibodies (ADA). The ADAs may be produced by the subject’s immune system in response to a therapeutic (e.g., a therapeutic comprising a TNFa inhibitor). The ADAs may recognize and / or bind the therapeutic, potentially reducing the efficacy of the therapeutic (e.g., neutralizes the therapeutic and / or triggers immune reactions against the therapeutic).

[0479] In some embodiments, the subject comprises neutralizing antibodies (nAB), which may inhibit the biological activity of a therapeutic (e.g., a therapeutic comprising a TNFa inhibitor). When nAb are present, they may prevent the therapeutic from binding to its target or interfere with its function, reducing its efficacy.

[0480] In some embodiments, the subject has received an anti-inflammatory medication. In some embodiments, the subject is receiving an anti-inflammatory medication. In some embodiments, the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline, thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab.

[0481] In some embodiments, the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone. In some embodiments, the subject has received or is receiving about 7.5 to about 25 mg / day of the corticosteroid.

[0482] In some embodiments, the subject has received or is receiving a therapeutic selected from the group consisting of a short-acting beta-agonist (SABA) (e.g., albuterol, salbutamol), a Short-acting muscarinic antagonist (SAMA) (e.g., ipratropium bromide), a Long-acting beta-agonist (LABA) (e.g., formoterol or salmeterol), an Ultra-long-acting beta-agonist (Ultra-LABA) (e.g., indacaterol, vilanterol, or olodaterol), and a Long-acting muscarinic antagonist (LAMA) (e.g., tiotropium, umeclidinium, aclidinium, or glycopyrronium).Doses / Phases

[0483] In some embodiments, the composition is administered to the subject as a first dose. The first dose may comprise administering the composition to the subject in an amount of about 0.5 mg / kg, about 1.0 mg / kg, about 1.5 mg / kg, about 2.0 mg / kg, about 2.5 mg / kg, about 3.0 mg / kg, about 3.5 mg / kg, about 4.0 mg / kg, about 4.5 mg / kg, about 5.0 mg / kg, about 5.5 mg / kg, or about 6.0 mg / kg.

[0484] In some embodiments, the composition is administered to the subject as a first dose in an amount of at least 0.5 mg / kg, at least 1.0 mg / kg, at least 1.5 mg / kg, at least 2.0 mg / kg, at least 2.5 mg / kg, at least 3.0 mg / kg, at least 3.5 mg / kg, at least 4.0 mg / kg, at least 4.5 mg / kg, at least 5.0 mg / kg, at least 5.5 mg / kg, or at least 6.0 mg / kg.

[0485] In some embodiments, the composition is administered to the subject as a first dose in an amount of at least about 0.5 mg / kg, at least about 1.0 mg / kg, at leastabout 1.5 mg / kg, at least about 2.0 mg / kg, at least about 2.5 mg / kg, at least about 3.0 mg / kg, at least about 3.5 mg / kg, at least about 4.0 mg / kg, at least about 4.5 mg / kg, at least about 5.0 mg / kg, at least about 5.5 mg / kg, or at least about 6.0 mg / kg.

[0486] In some embodiments, the first dose may comprise administering the composition to the subject in an amount of about 2 mg / kg or about 4 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of about 2 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of about 4 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of about 2 mg / kg once every 2 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of about 4 mg / kg once every 2 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of about 2 mg / kg once every 4 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of about 4 mg / kg once every 4 weeks for the first period of time.

[0487] In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least 2 mg / kg or at least 4 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least 2 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least 4 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least 2 mg / kg once every 2 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least 4 mg / kg once every 2 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least 2 mg / kg once every 4 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least 4 mg / kg once every 4 weeks for the first period of time.

[0488] In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least about 2 mg / kg or at least about 4 mg / kg. In some embodiments, the first dose may comprise administering thecomposition to the subject in an amount of at least about 2 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least about 4 mg / kg. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least about 2 mg / kg once every 2 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least about 4 mg / kg once every 2 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least about 2 mg / kg once every 4 weeks for the first period of time. In some embodiments, the first dose may comprise administering the composition to the subject in an amount of at least about 4 mg / kg once every 4 weeks for the first period of time.

[0489] In some embodiments, the first dose of composition is administered about once a week, about once every two weeks, about once every three weeks, about once every four weeks, about once every 5 weeks, or about once every 6 weeks for a first period of time.

[0490] In some embodiments, the first dose of composition is administered at least once a week, at least once every two weeks, at least once every three weeks, at least once every four weeks, at least once every 5 weeks, or at least once every 6 weeks for a first period of time.

[0491] In some embodiments, the first dose of composition is administered at least about once a week, at least about once every two weeks, at least about once every three weeks, at least about once every four weeks, at least about once every 5 weeks, or at least about once every 6 weeks for a first period of time.

[0492] In some embodiments, the first period of time is about 6 weeks to about 24 weeks. In some embodiments, the first period of time is about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 14 weeks, about 15 weeks, about 16 weeks, about 18 weeks, about 20 weeks, about 22 weeks, or about 24 weeks.

[0493] In some embodiments, the first period of time is at least 6 weeks to at least 24 weeks. In some embodiments, the first period of time is at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 14 weeks, at least 15 weeks, atleast 16 weeks, at least 18 weeks, at least 20 weeks, at least 22 weeks, or at least 24 weeks.

[0494] In some embodiments, the first period of time is at least about 6 weeks to at least about 24 weeks. In some embodiments, the first period of time is at least about 6 weeks, at least about 8 weeks, at least about 10 weeks, at least about 12 weeks, at least about 14 weeks, at least about 15 weeks, at least about 16 weeks, at least about 18 weeks, at least about 20 weeks, at least about 22 weeks, or at least about 24 weeks.

[0495] In some embodiments, the subject is administered a cumulative dose of about 6 mg / kg to about 30 mg / kg. In some embodiments, the subject is administered a cumulative dose of about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, or about 20 mg / kg of the composition during the first period of time.

[0496] In some embodiments, the subject is administered a cumulative dose of at least 6 mg / kg to at least 30 mg / kg. In some embodiments, the subject is administered a cumulative dose of at least 2 mg / kg, at least 3 mg / kg, at least 4 mg / kg, at least 5 mg / kg, at least 6 mg / kg, at least 7 mg / kg, at least 8 mg / kg, at least 9 mg / kg, at least 10 mg / kg, at least 11 mg / kg, at least 12 mg / kg, at least 13 mg / kg, at least 14 mg / kg, at least 15 mg / kg, at least 16 mg / kg, at least 17 mg / kg, at least 18 mg / kg, at least 19 mg / kg, or at least 20 mg / kg of the composition during the first period of time.

[0497] In some embodiments, the subject is administered a cumulative dose of at least about 6 mg / kg to at least about 30 mg / kg. In some embodiments, the subject is administered a cumulative dose of at least about 2 mg / kg, at least about 3 mg / kg, at least about 4 mg / kg, at least about 5 mg / kg, at least about 6 mg / kg, at least about 7 mg / kg, at least about 8 mg / kg, at least about 9 mg / kg, at least about 10 mg / kg, at least about 11 mg / kg, at least about 12 mg / kg, at least about 13 mg / kg, at least about 14 mg / kg, at least about 15 mg / kg, at least about 16 mg / kg, at least about 17 mg / kg, at least about 18 mg / kg, at least about 19 mg / kg, or at least about 20 mg / kg of the composition during the first period of time.

[0498] In some embodiments, the composition is administered to the subject as a second dose. In some embodiments, the second dose comprises administering the composition to the subject in an amount of about 0.5 mg / kg, about 1.0 mg / kg, about 1.5 mg / kg, about 2.0 mg / kg, about 2.5 mg / kg, about 3.0 mg / kg, about 3.5 mg / kg, about 4.0 mg / kg, about 4.5 mg / kg, about 5.0 mg / kg, about 5.5 mg / kg, or about 6.0 mg / kg.

[0499] In some embodiments, the composition is administered to the subject as a second dose in an amount of at least 0.5 mg / kg, at least 1.0 mg / kg, at least 1.5 mg / kg, at least 2.0 mg / kg, at least 2.5 mg / kg, at least 3.0 mg / kg, at least 3.5 mg / kg, at least 4.0 mg / kg, at least 4.5 mg / kg, at least 5.0 mg / kg, at least 5.5 mg / kg, or at least 6.0 mg / kg.

[0500] In some embodiments, the composition is administered to the subject as a second dose in an amount of at least about 0.5 mg / kg, at least about 1.0 mg / kg, at least about 1.5 mg / kg, at least about 2.0 mg / kg, at least about 2.5 mg / kg, at least about 3.0 mg / kg, at least about 3.5 mg / kg, at least about 4.0 mg / kg, at least about 4.5 mg / kg, at least about 5.0 mg / kg, at least about 5.5 mg / kg, or at least about 6.0 mg / kg.

[0501] In some embodiments, the second dose of composition is administered about once a week, about once every two weeks, about once every three weeks, about once every four weeks, about once every 5 weeks, or about once every 6 weeks for a second period of time.

[0502] In some embodiments, the second dose of composition is administered at least once a week, at least once every two weeks, at least at least once every three weeks, at least once every four weeks, at least once every 5 weeks, or at least once every 6 weeks for a second period of time.

[0503] In some embodiments, the second dose of composition is administered at least about once a week, at least about once every two weeks, at least about once every three weeks, at least about once every four weeks, at least about once every 5 weeks, or at least about once every 6 weeks for a second period of time.

[0504] In some embodiments, the second period of time is about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 14 weeks, about 15 weeks, about 16 weeks, about 18 weeks, about 20 weeks, about 22 weeks, or about 24 weeks.

[0505] In some embodiments, the second period of time is at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 14 weeks, at least 15weeks, at least 16 weeks, at least 18 weeks, at least 20 weeks, at least 22 weeks, or at least 24 weeks.

[0506] In some embodiments, the second period of time is at least about 6 weeks, at least about 8 weeks, at least about 10 weeks, at least about 12 weeks, at least about 14 weeks, at least about 15 weeks, at least about 16 weeks, at least about 18 weeks, at least about 20 weeks, at least about 22 weeks, or at least about 24 weeks.

[0507] In some embodiments, the second dose is about two times greater than the first dose.

[0508] In some embodiments, the second dose is at least two times greater than the first dose.

[0509] In some embodiments, the second dose is at least about two times greater than the first dose.

[0510] In some embodiments, the second dose is about the same at the first dose.

[0511] In some embodiments, the administration frequency of the second dose comprises the same administration frequency of the first dose.

[0512] In some embodiments, the administration frequency of the second dose consists of the same administration frequency of the first dose.

[0513] In some embodiments, the administration frequency of the second dose is about two times greater than the administration frequency of the first dose

[0514] In some embodiments, the first dose and the second dose are each administered about once every four weeks.

[0515] In some embodiments, the first dose is administered about once every four weeks and the second dose is administered about once every two weeks.

[0516] In some embodiments, the subject is administered a cumulative dose of about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, or about 20 mg / kg of the composition during the second period of time.

[0517] In some embodiments, the subject is administered a cumulative dose of at least 5 mg / kg, at least 6 mg / kg, at least 7 mg / kg, at least 8 mg / kg, at least 9 mg / kg, atleast 10 mg / kg, at least 11 mg / kg, at least 12 mg / kg, at least 13 mg / kg, at least 14 mg / kg, at least 15 mg / kg, at least 16 mg / kg, at least 17 mg / kg, at least 18 mg / kg, at least 19 mg / kg, or at least 20 mg / kg of the composition during the second period of time.

[0518] In some embodiments, the subject is administered a cumulative dose of at least about 5 mg / kg, at least about 6 mg / kg, at least about 7 mg / kg, at least about 8 mg / kg, at least about 9 mg / kg, at least about 10 mg / kg, at least about 11 mg / kg, at least about 12 mg / kg, at least about 13 mg / kg, at least about 14 mg / kg, at least about 15 mg / kg, at least about 16 mg / kg, at least about 17 mg / kg, at least about 18 mg / kg, at least about 19 mg / kg, or at least about 20 mg / kg of the composition during the second period of time.

[0519] In some embodiments, the composition is administered to the subject as a third dose. In some embodiments, the third dose comprises administering the composition to the subject in an amount of about 0.5 mg / kg, about 1.0 mg / kg, about 1.5 mg / kg, about 2.0 mg / kg, about 2.5 mg / kg, about 3.0 mg / kg, about 3.5 mg / kg, about 4.0 mg / kg, about 4.5 mg / kg, about 5.0 mg / kg, about 5.5 mg / kg, or about 6.0 mg / kg.

[0520] In some embodiments, the composition is administered to the subject as a third dose in an amount of at least 0.5 mg / kg, at least 1.0 mg / kg, at least 1.5 mg / kg, at least 2.0 mg / kg, at least 2.5 mg / kg, at least 3.0 mg / kg, at least 3.5 mg / kg, at least 4.0 mg / kg, at least 4.5 mg / kg, at least 5.0 mg / kg, at least 5.5 mg / kg, or at least 6.0 mg / kg.

[0521] In some embodiments, the composition is administered to the subject as a third dose in an amount of at least about 0.5 mg / kg, at least about 1.0 mg / kg, at least about 1.5 mg / kg, at least about 2.0 mg / kg, at least about 2.5 mg / kg, at least about 3.0 mg / kg, at least about 3.5 mg / kg, at least about 4.0 mg / kg, at least about 4.5 mg / kg, at least about 5.0 mg / kg, at least about 5.5 mg / kg, or at least about 6.0 mg / kg.

[0522] In some embodiments, the third dose of composition is administered about once a week, about once every two weeks, about once every three weeks, about once every four weeks, about once every 5 weeks, or about once every 6 weeks for a third period of time.

[0523] In some embodiments, the third dose of composition is administered at least once a week, at least once every two weeks, at least at least once every threeweeks, at least once every four weeks, at least once every 5 weeks, or at least once every 6 weeks for a third period of time.

[0524] In some embodiments, the third dose of composition is administered at least about once a week, at least about once every two weeks, at least about once every three weeks, at least about once every four weeks, at least about once every 5 weeks, or at least about once every 6 weeks for a third period of time.

[0525] In some embodiments, the third period of time is about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 14 weeks, about 15 weeks, about 16 weeks, about 18 weeks, about 20 weeks, about 22 weeks, or about 24 weeks.

[0526] In some embodiments, the third period of time is at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 14 weeks, at least 15 weeks, at least 16 weeks, at least 18 weeks, at least 20 weeks, at least 22 weeks, or at least 24 weeks.

[0527] In some embodiments, the third period of time is at least about 6 weeks, at least about 8 weeks, at least about 10 weeks, at least about 12 weeks, at least about 14 weeks, at least about 15 weeks, at least about 16 weeks, at least about 18 weeks, at least about 20 weeks, at least about 22 weeks, or at least about 24 weeks.

[0528] In some embodiments, the subject is administered a cumulative dose of about 20 mg / kg, about 22 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 28 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 44 mg / kg, about 46 mg / kg, about 48 mg / kg, about 50 mg / kg, about 52 mg / kg, about 54 mg / kg, about 56 mg / kg, about 58 mg / kg, about 60 mg / kg, about 65 mg / kg, about 70 mg / kg, or about 75 mg / kg of the composition, across all periods of time.

[0529] In some embodiments, the subject is administered a cumulative dose of at least 20 mg / kg, at least 22 mg / kg, at least 24 mg / kg, at least 25 mg / kg, at least 26 mg / kg, at least 28 mg / kg, at least 30 mg / kg, at least 35 mg / kg, at least 40 mg / kg, at least 44 mg / kg, at least 46 mg / kg, at least 48 mg / kg, at least 50 mg / kg, at least 52 mg / kg, at least 54 mg / kg, at least 56 mg / kg, at least 58 mg / kg, at least 60 mg / kg, at least 65 mg / kg, at least 70 mg / kg, or at least 75 mg / kg of the composition, across all periods of time.

[0530] In some embodiments, the subject is administered a cumulative dose of at least about 20 mg / kg, at least about 22 mg / kg, at least about 24 mg / kg, at least about 25 mg / kg, at least about 26 mg / kg, at least about 28 mg / kg, at least about 30 mg / kg, at least about 35 mg / kg, at least about 40 mg / kg, at least about 44 mg / kg, at least about 46 mg / kg, at least about 48 mg / kg, at least about 50 mg / kg, at least about 52 mg / kg, at least about 54 mg / kg, at least about 56 mg / kg, at least about 58 mg / kg, at least about 60 mg / kg, at least about 65 mg / kg, at least about 70 mg / kg, or at least about 75 mg / kg of the composition, across all periods of time.

[0531] In some embodiments, the compositions are administered using an infusion (e.g., intravenous infusion). In some embodiments, the infusion is administered over a period of about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, or about 5 hours.

[0532] In some embodiments, the infusion is administered over a period of at least 30 minutes, at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, or at least 5 hours.

[0533] In some embodiments, the infusion is administered over a period of at least about 30 minutes, at least about 1 hour, at least about 2 hours, at least about 3 hours, at least about 4 hours, or at least about 5 hours.

[0534] In some embodiments, the subject is administered at least 2 doses, at least 3 doses, at least 4 doses, at least 5 doses, at least 6 doses, at least 7 doses, or at least 8 doses of the composition.

[0535] In some embodiments, the subject is administered at least 3 doses over a 12-week period of time. In some embodiments, the subject is administered at least 6 doses over a 12-week period of time.Outcomes of Administration and Uses of the Compositions

[0536] In some embodiments, the subject administered a composition of the present technology experiences a reduction in a level of one or more transcripts selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (I L6), interleukin 2 receptor (IL2R), tumor necrosis factor alpha (TNFa), C-Reactive Protein (CRP), interleukin 1 B (IL1 B), interleukin 12 (IL12), interleukin 18 (IL18), interferon gamma (IFNG), interleukin 8 (IL8), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JunB), mitogen-activated protein kinase (MKP1 ), TNF alpha induced protein 1 (TNFAIP1 ), TNF alpha induced protein 2 (TNFAIP2), TNF alpha induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL32), intercellular adhesion molecule 1 (IGAM-1), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1A member 1 (SCGB1A1), serum amyloid A1 (SAA1), and vascular adhesion molecule 1 (VCAM-1), relative to a control.

[0537] In some embodiments, the subject administered a composition of the present technology experiences a reduction in a level of one or more proteins selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL-6), interleukin 2 receptor (IL-2R), tumor necrosis factor alpha (TNF-a), C-Reactive Protein (CRP), interleukin 1 B (IL-1 B), interferon gamma (IFN-y), interleukin 8 (IL-8), interleukin 12 (IL-12), interleukin 18 (IL-18), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JUNB), mitogen-activated protein kinase phosphatase 1 (MKP-1), TNF alpha-induced protein 1 (TNFAIP1), TNF alpha-induced protein 2 (TNFAIP2), TNF alpha-induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL-32), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1A member 1 (SCGB1A1), serum amyloid A1 (SAA1 ), intercellular adhesion molecule 1 (ICAM-1 ), and vascular adhesion molecule 1 (VCAM-1) relative to a control.

[0538] In some embodiments, the subject administered a composition of the present technology experiences an improvement in one or more of a Forced Vital Capacity (FVC) measurement, a King's Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score relative to the control or baseline.

[0539] In some embodiments, the subject administered a composition of the present technology experiences a decrease or a stabilization of a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) relative to the control or baseline.

[0540] In some embodiments, the subject administered a composition of the present technology experiences an improvement in one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) relative to the control or baseline.

[0541] In some embodiments, the subject administered a composition of the present technology experiences an increase in one or more of a Forced Vital Capacity (FVC) measurement, a Forced Expiratory Volume in 1 second (FEV1) measurement, a Leicester Cough Questionnaire (LCQ) score, a Short Form 36 Health Survey (SF-36) score, a King’s Sarcoidosis Questionnaire (KSQ) score (e.g., a KSQ General Health Status Module or a KSQ lung score), a Steroid-toxicity scale (STS) score, or a 6-minute walk test (6MWT) distance relative to a control.

[0542] In some embodiments, the subject administered a composition of the present technology experiences an increase in pulmonary function as measured by pulmonary imaging. The pulmonary imaging may comprise high-resolution computed tomography.

[0543] In some embodiments, the subject administered a composition of the present technology experiences a reduction in one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, Modified Medical Research Council (mMRC) Dyspnea Scale score, a Saint George's Respiratory Questionnaire (SGRQ) score, or a Borg's CR10 dyspnea score relative to a control.

[0544] In some embodiments, the subject administered a composition of the present technology experiences a reduction in stage on the Scadding CXR relative to a control.

[0545] In some embodiments, the subject administered a composition of the present technology experiences an improved quality of life relative to a control. In some embodiments, the quality of life is assessed by one or more of a KSQ score, a LCQ score, a PGA score, a FAS score, a mMRC Dyspnea Scale score, a SF-36 score, or a steroid toxicity questionnaire (STQ) score.

[0546] In some embodiments, the subject administered a composition of the precent technology experiences an improvement in one or more limitations selected from the group consisting of a limitation in physical activities because of health problems, a limitation in social activities because of physical or emotional problems, limitations in usual role activities because of physical health problems, and a limitation s in usual role activities because of emotional problems, relative to a control.

[0547] In some embodiments, the subject administered a composition of the precent technology experiences a reduction in bodily pain relative to a control.

[0548] In some embodiments, the subject administered a composition of the precent technology experiences an improvement in mental health relative to a control.

[0549] In some embodiments, the subject administered a composition of the precent technology experiences an increase in vitality (e.g., increase in energy and / or reduction in fatigue) relative to a control.

[0550] In some embodiments, the subject administered a composition of the present technology experiences an improvement in general health perception relative to a control.

[0551] In some embodiments, the subject administered a composition of the present technology experiences an increase in lifespan relative to a control.

[0552] In some embodiments, the subject administered a composition of the present technology experiences a reduced need (e.g., frequency of, dosage of, or duration of administration of) for an anti-inflammatory medication relative to a control. In some embodiments, the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline, thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab. In some embodiments, the corticosteroid is selected fromthe group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone.

[0553] In some embodiments, the subject administered a composition of the present technology experiences a reduction in corticosteroid use relative to a control or baseline.

[0554] In some embodiments, the subject administered a composition of the present technology experiences a reduction in a granuloma formation or a granuloma size relative to a control. In some embodiments, the granuloma is a skin granuloma, a lung granuloma, a lymph node granuloma, an ocular granuloma, a liver granuloma, a spleen granuloma, a cardiac granuloma, or a rheumatoid granuloma.

[0555] In some embodiments, the subject administered a composition of the present technology experiences a reduction in a calcitriol level, a neopterin level, a soluble IL-2R (s I L-2R) level, or a lysozyme level, in the subject relative to a control.

[0556] In some embodiments, the subject administered a composition of the present technology experiences a reduction in immune cell anergy relative to a control.

[0557] In some embodiments, the subject administered a composition of the present technology experiences an improvement in a Steroid Toxicity Questionnaire (STQ) score relative to a control or baseline.

[0558] In some embodiments, the subject administered a composition of the present technology experiences an improvement in Likert scale assessment of High-Resolution Computed Tomography (HRCT) relative to a control or baseline.

[0559] In some embodiments, the subject administered a composition of the present technology does not exhibit an increase in anti-drug antibodies (ADAs) relative to a control or baseline.

[0560] In some embodiments, the subject administered a composition of the present technology does not exhibit an increase in neutralizing antibodies (Nabs) relative to a control or baseline.

[0561] In some embodiments, the subject administered a composition of the present technology experiences an improvement in a Likert scale assessment of High-resolution computed tomography (HRCT) relative to a control or baseline.

[0562] In some embodiments, the subject administered a composition of the present technology does not experience adverse events (AEs) relative to a control or baseline.

[0563] In some embodiments, the subject administered a composition of the present technology does not experience treatment-emergent adverse events (TEAEs) relative to a control or baseline.

[0564] In some embodiments, the subject administered a composition of the present technology does not experience serious adverse events (SAEs) relative to a control or baseline.

[0565] In some embodiments, the subjected administered a dose of one or more compositions of the present technology exhibits one or more of:

[0566] (a) a reduction in an ACE2 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0567] (b) a reduction in an ACE2 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0568] (c) a reduction in an IL6 transcript level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0569] (d) a reduction in an IL6 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0570] (e) a reduction in an IL2R transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0571] (f) a reduction in an IL2R transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0572] (g) a reduction in a TNFa transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0573] (h) reduction in a TNFa transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0574] (i) a reduction in a GRP transcript level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0575] (j) a reduction in a GRP transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0576] (k) a reduction in an IL1B transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0577] (I) a reduction in an IL1 B transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0578] (m) a reduction in an IL12 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0579] (n) a reduction in an IL12 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0580] (o) a reduction in an IL18 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0581] (p) a reduction in an IL18 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0582] (q) a reduction in an IFN-y transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0583] (r) reduction in an IFN-y transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0584] (s) a reduction in an IL8 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0585] (t) a reduction in an IL8 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0586] (u) a reduction in a MCP-1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0587] (v) a reduction in a MCP-1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0588] (w) a reduction in a CXCL1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0589] (x) a reduction in a CXCL1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0590] (y) a reduction in a CXCL2 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0591] (x) a reduction in a CXCL2 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0592] (z) a reduction in a CXCL3 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0593] (aa) a reduction in a CXCL3 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0594] (cc) a reduction in an EGR1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0595] (cc) a reduction in an EGR1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0596] (dd) a reduction in a JunB transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0597] (ee) a reduction in a JunB transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0598] (ft) a reduction in a MKP1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0599] (gg) a reduction in a MKP1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0600] (hh) a reduction in a TNFAIP1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0601] (ii) reduction in a TNFAIP1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0602] (jj) a reduction in a TNFAIP2 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0603] (kk) reduction in a TNFAIP2 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0604] (II) a reduction in a TNFAIP3 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0605] (mm) a reduction in a TNFAIP3 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0606] (nn) a reduction in a SDC4 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0607] (oo) a reduction in a SDC4 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0608] (pp) a reduction in a SOD2 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0609] (qq) a reduction in a SOD2 transcript level by about less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0610] (rr) a reduction in a COX2 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0611] (ss) reduction in a COX2 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0612] (tt) a reduction in a IL32 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0613] (uu) a reduction in a IL32 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0614] (w) a reduction in an ICAM-1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0615] (ww) a reduction in an ICAM-1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0616] (xx) a reduction in a KL-6 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0617] (yy) reduction in a KL-6 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0618] (zz) a reduction in a CXCL10 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0619] (aaa) a reduction in a CXCL10 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0620] (bbb) a reduction in a CXCL9 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0621] (ccc) a reduction in a CXCL9 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0622] (ddd) a reduction in a CH IT1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0623] (eee) a reduction in a CHIT1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0624] (fff) a reduction in a SCGB1A1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0625] (ggg) a reduction in a SCGB1A1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0626] (hhh) a reduction in a SAA1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0627] (iii) a reduction in a SAA1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0628] (jjj) a reduction in a VCAM-1 transcript level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0629] (kkk) a reduction in a VCAM-1 transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0630] (III) a reduction in an Angiotensin Converting Enzyme (ACE) transcript level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control;

[0631] (mmm) reduction in an ACE transcript level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0632] (nnn) a reduction in a level of Soluble Tumor Necrosis Factor Alpha (sTNFa) transcript level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0633] (ooo) a reduction in a sTNFa by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0634] (ppp) a reduction in an ACE2 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0635] (qqq) a reduction in an ACE2 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0636] (rrr) a reduction in an IL-6 protein level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0637] (sss) a reduction in an IL-6 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0638] (ttt) a reduction in an IL-2R protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0639] (uuu) a reduction in an IL-2R protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0640] (vvv) a reduction in a TNF-a protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0641] (www) a reduction in a TNF-a protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0642] (xxx) a reduction in a CRP protein level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0643] (yyy) a reduction in a CRP protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0644] (zzz) a reduction in an IL-1 B protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0645] (aaaa) a reduction in an IL-1 B protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0646] (bbbb) a reduction in a MCP-1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0647] (cccc) a reduction in a MCP-1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0648] (dddd) a reduction in a CXCL1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0649] (eeee) a reduction in a CXCL1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0650] (ffff) a reduction in a CXCL2 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0651] (gggg) reduction in a CXCL2 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0652] (hhhh) a reduction in a CXCL3 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0653] (iiii) reduction in a CXCL3 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0654] (jjjj) a reduction in an EGR1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0655] (kkkk) a reduction in an EGR1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0656] (IIII) a reduction in a JUNB protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0657] (mmmm) a reduction in a JUNB protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0658] (nnnn) a reduction in a MKP-1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0659] (oooo) a reduction in a MKP-1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0660] (PPPP) a reduction in a TNFAIP1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0661] (qqqq) a reduction in a TNFAIP1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0662] (rrrr) a reduction in a TNFAIP2 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0663] (ssss) a reduction in a TNFAIP2 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0664] (tttt) a reduction in a TNFAIP3 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0665] (uuuu) a reduction in a TNFAIP3 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0666] (ww) a reduction in a SDC4 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0667] (wwww) a reduction in a SDC4 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0668] (xxxx) a reduction in a SOD2 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0669] (yyyy) a reduction in a SOD2 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0670] (zzzz) a reduction in a COX2 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0671] (aaaaa) a reduction in a COX2 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0672] (bbbbb) a reduction in an IL-32 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0673] (ccccc) reduction in an IL-32 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0674] (ddddd) a reduction in a KL-6 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0675] (eeeee) a reduction in a KL-6 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0676] (fffff) a reduction in a CXCL10 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0677] (ggggg) a reduction in a CXCL10 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0678] (hhhhh) a reduction in a CXCL9 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0679] (iiiii) a reduction in a CXCL9 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0680] (jjjjj) a reduction in a CHIT1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0681] (kkkkk) a reduction in a CHIT1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0682] (IIIII) a reduction in a SCGB1A1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0683] (mmmmm) a reduction in a SCGB1 A1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0684] (nnnnn) a reduction in a SAA1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0685] (ooooo) a reduction in a SAA1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0686] (PPPPP) a reduction in an ICAM-1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0687] (qqqqq) a reduction in an ICAM-1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0688] (rrrrr) a reduction in a VCAM-1 protein level by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0689] (sssss) a reduction in a VCAM-1 protein level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0690] (ttttt) a reduction in an ACE level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control or baseline;

[0691] (uuuuu) a reduction in an ACE level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0692] (wwv) a reduction in a sTNFa level by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control or baseline;

[0693] (wwwww) a reduction in a sTNFa level by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0694] (xxxxx) an increase in an FVC measurement by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0695] (yyyyy) an increase in an FVC measurement by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0696] (zzzzz) an improvement in an FVC measurement by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control or baseline;

[0697] (aaaaaa) an improvement in an FVC measurement by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0698] (bbbbbb) an increase in an FEV1 measurement by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0699] (cccccc) an increase in an FEV1 measurement by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0700] (dddddd) an increase in a LCQ score by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 points relative to a control;

[0701] (eeeeee) an increase in a LCQ score by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0702] (ffffff) a reduction in a STQ score by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline;

[0703] (gggggg) a reduction in an STQ score by less than about 10%, 5%, 4%, 3%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0704] (hhhhhh) an increase in a SF-36 score by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to a control;

[0705] (iiiiii) an increase in a SF-36 score by less than about 2, 1.8, 1.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 relative to a control.

[0706] (jjjjjj) an increase in a KSQ score by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to a control;

[0707] (kkkkkk) an increase in a KSQ score by less than about 2, 1.8, 1.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 relative to a control.

[0708] an increase in a STS score by at least 1, 2, 3, 4, 5, or 6 points relative to a control;

[0709] (mmmmmm) an increase in an STS score by less than about 2, 1.8, 1.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 relative to a control;

[0710] (nnnnnn) an increase in 6MWT distance by at least 10m, 20m, 30m, 40m, 50m, 60m, 70m, 80m, 90m, 100m, 125m, 150m, 175m, 200m, 250m, 300m, 350m, 400m, 450m, or 500m relative to a control;

[0711] (oooooo) an increase in 6MWT distance by less than 10m, 8m, 6m, 5m, 4m, 3m, 2m, 1,8m, 1,6m, 1,4m, 1,2m, 1 m, 0.8m, 0.6m, 0.4m, 0.2m, or 0.1 m relative to a control

[0712] (pppppp) a reduction in a PGA score by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points relative to a control;

[0713] (qqqqqq) a reduction in a PGA score by less than about 5 points, 4 points, 3 points, 2 points, 1.8 point, 1.6 points, 1.4 points, 1.2 points, 1 point, 0.8 points, 0.6 points, 0.4 points, 0.2 points, or 0.1 points relative to a control.

[0714] (rrrrrr) a reduction in a FAS score by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to a control;

[0715] (ssssss) a reduction in a FAS score by less than about 5, 4, 3, 2, 1.8, 1.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 points relative to a control;

[0716] (tttttt) a reduction in a mMRC Scale score by at least about 1, 2, 3, or 4 grades relative to a control;

[0717] (uuuuuu) a reduction in a mMRC scale score by less than about 2, 1.8,.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 grades relative to a control;

[0718] (www) an improvement in a mMRC Scale score by at least about 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline;

[0719] (wwwwww) an improvement in a mMRC Scale score by less than about 2, 1.8,.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 points relative to a control;

[0720] (xxxxxx) a reduction in a SGRQ score by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to a control;

[0721] (yyyyyy) a reduction in a SGRQ score by less than about 2, 1.8,.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 points relative to a control;

[0722] (zzzzzz) a reduction in a Borg’s CR10 dyspnea score by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points relative to a control;

[0723] (aaaaaaa) a reduction in a Borg’s CR10 dyspnea score by less than about 2, 1.8,.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, 0.2, or 0.1 points relative to a control;

[0724] (bbbbbbb) an improvement in a 6 Minute Walking Distance (6MWD) by about 3 min, 5 min, 10 min, 20 min, or 30 min relative to a control or baseline;

[0725] (ccccccc) an improvement in a 6MWD by less than about 5 min, 4 min, 3 min, 2 min, 1.8 min, 0.6 min, 1.4 min, 1.2 min, 1 min, 0.8 min, 0.6 min, 0.4 min, 0.2 min relative to a control;

[0726] (ddddddd) a reduction in a corticosteroid use by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control;

[0727] (eeeeeee) a reduction in a corticosteroid use by less than about 5%, 4%, 3%, 2%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0728] (fffffff) a reduction in a granuloma formation by about 1 %, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%, relative to a control;

[0729] (ggggggg) a reduction in a granuloma formation by less than about 5%, 4%, 3%, 2%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0730] (hhhhhhh) a reduction in a granuloma size by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%, relative to a control;

[0731] (iiiiiii) a reduction in a granuloma size by less than about 5%, 4%, 3%, 2%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0732] (jjjjjjj) a reduction in a calcitriol level by at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0733] (kkkkkkk) reduction in a calcitriol level by less than about 5%, 4%, 3%, 2%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0734] a reduction in a neopterin level by at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0735] (mmmmmmm) reduction in a neopterin level by less than about 5%, 4%, 3%, 2%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0736] (nnnnnnn) a reduction in a lysozyme level by at least about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0737] (ooooooo) a reduction in a lysozyme level by less than about 5%, 4%, 3%, 2%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0738] (ppppppp) a reduction in a slL-2R level by at least about 2%, 3%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to a control;

[0739] (qqqqqqq) a reduction in a slL-2R level by less than about 5%, 4%, 3%, 2%, 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, or 0.2% relative to a control;

[0740] (rrrrrrr) an increase in a Scadding CXR stage by at least 1, 2, 3, or 4 stages relative to a control; and

[0741] (sssssss) an increase in a Scadding CXR stage by less than about 2, 1.8, 1.6, 1.4, 1.2, 1.0, 0.8, 0.6, 0.4, or 0.2 stages relative to a control.

[0742] An enhanced or more effective outcome of any of the methods of the present technology may be achieved by using the anti-TNFa antibodies compared to use of a corticosteroid at the same or different dosages. In some embodiments, the methods of the present technology comprise a superior dose effect using the anti-TNFa antibodies of the present technology, relative to use of a corticosteroid in place of the anti-TNFa antibodies. In some embodiments, the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone

[0743] In some embodiments, the methods of the present technology do not have or have a reduction in a side effect compared to administration a corticosteroid used at the same or at a lower dosage than the anti-TNFa antibodies. Nonlimiting examples of such side effects include a steroid toxicity. Steroid toxicity may be assessed and / or determined using a steroid toxicity questionnaire (STQ) score.EXAMPLESExample 1: Assessing XTMAB-16 in Subjects with Pulmonary Sarcoidosis

[0744] The present example will be conducted to as a Multiple Ascending Dose (MAD)ZProof of Concept (POC) Study (hereafter referred to as Phase 2 Program) of XTMAB-16 in subjects with pulmonary sarcoidosis with or without extrapulmonary involvement. The study is comprised of two parts: Part A will be a randomized doubleblind placebo-controlled multiple dose-escalating study, and Part B will be a randomized double-blind placebo-controlled POC study (FIG. 1 ). The present example incorporates Example 3 of the present disclosure by reference.

[0745] The objective of Part A is to evaluate the safety and tolerability of MADs of XTMAB-16, and to determine the recommended Phase 2 dose and frequency for Part B for XTMAB-16 administration in subjects with pulmonary sarcoidosis with or without extrapulmonary manifestations. Part A objectives and endpoints are outlined in Table 6-Table 8.

[0746] The objective of Part B is to confirm preliminary efficacy of XTMAB-16 as measured by the ability to reduce background oral corticosteroid use in subjects with pulmonary sarcoidosis with or without extrapulmonary manifestations. Part B objectives are outlined in Table 9.

[0747] The rationale for this study is to conduct dose range finding to identify the recommended Phase 2 dose (RP2D) for Part B and characterize a variety of clinical and biomarker outcome measures to demonstrate efficacy and POC for XTMAB-16 in this subject population.Table 6: Part A (MAD) Primary Objectives and EndpointsTable 7: Part A (MAD) Secondary Objectives and EndpointsTable 8: Part A (MAD) Exploratory Objectives and EndpointsAbbreviations: 6MWD = 6 minute walk distance; ACE = angiotensin converting enzyme; ADA = anti-drug antibodies; AE = adverse event; AESI = adverse events of special interest; AUC = area under the curve; ALIEC = area under the effect curve; Caverage = average concentration; Cmax = Maximum observed concentration; CRP = C-reactive protein; Ctrough = trough concentration; DLT = dose limiting toxicities; Emax,obs = maximum observed effect; EOI = end of infusion; FAS = fatigue assessment scale; FVC = forced vital capacity; HRCT = high-resolution computed tomography; IL-1b = interleukin 1b; IL-6 = interleukin-6; KSQ = King’s Sarcoidosis Questionnaire; LCQ = Leicester Cough Questionnaire; MAD = multiple ascending dose; mg = milligram; mMRC = Modified Medical Research Council; nAb = neutralizing antibodies; PD = pharmacodynamics; PGA = Patient Global Assessment;PK = pharmacokinetics; QoL = quality of life; SAE = serious adverse event; SF-36 = Short Form-36; sIL 2R = soluble interleukin-2 receptor; sTNFa = soluble tumor necrosis factor a; STQ = steroid toxicity questionnaire;tEmax.obs = time to reach maximum observed effect.Table 9: Part B (POC) Primary, Secondary, and Exploratory Objectives and EndpointsAbbreviations: 6MWD = 6-minute walk distance; ACE = angiotensin converting enzyme; ADA = anti-drug antibodies; AE = adverse event; AUC = area under the concentrationtime curve; Caverage = average concentration;Cmax = maximum observed concentration; GRP = C--reactive protein; Gtrough = trough concentration; FAS = fatigue assessment scale; FVC = forced vital capacity; HRCT = high-resolution computed tomography;IL-1 b = interleukin-1 b; IL-6 = interleukin-6; KSQ = King’s Sarcoidosis Questionnaire; LCQ = Leicester Cough Questionnaire; mg = milligram; mMRC = Modified Medical Research Council; nAb = neutralizing antibodies; PD = pharmacodynamics; PGA = patient global assessment; PK = pharmacokinetics; POC = proof of concept;SAE = serious adverse event; SF-36 = Short Form-36; sIL 2R = soluble interleukin-2 receptor; sTNFa = soluble tumor necrosis factor a; STQ = steroid toxicity questionnaire. Overall Design

[0748] This example comprises a Multiple Ascending Dose (MAD) / POC Study of XTMAB-16 to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and preliminary efficacy of XTMAB-16 in subjects with pulmonary sarcoidosis with or without extrapulmonary involvement. Part A will consist of a screening period of up to 42 days and a 12-week randomized double blind placebo-controlled treatment period of MAD regimens (FIG. 2), in which subjects will be randomized to XTMAB-16 or placebo in a 3:1 ratio per cohort (6 active, 2 placebo). A recommended phase 2 dose regimen (RP2D) will be determined from the results of Part A and Part B will commence as a double-blind placebo controlled POC study.

[0749] Subjects who complete Part A will maintain their assigned dose regimen in a rollover long-term open label safety study until all doses have been evaluated by the Data Safety Monitoring Committee (DSMC). Once the RP2D for Part B has been selected, subjects on treatment in the rollover study will transition to the RP2D.

[0750] Part B will include a double-blind placebo-controlled POC study (FIG. 3), with a 1:1 XTMAB-16 to placebo allocation ratio for 24 weeks of the RP2D determined in Part A. At the completion of Part B, all subjects who have completed up to 24 weeks of treatment and evaluations will be given the opportunity to rollover into the ongoing long-term open label safety study.Number of Subjects

[0751] Up to 32 subjects will be enrolled in Part A to receive either XTMAB-16 or placebo in a MAD fashion in planned cohorts for 12 weeks: 2 mg / kg every four weeks (Q4W) for 12 weeks (n = 6 active, 2 placebo), 4 mg / kg Q4W for 12 weeks (n = 6 active,2 placebo), 2 mg / kg every 2 weeks (Q2W) for 12 weeks (n = 6 active, 2 placebo), 4 mg / kg Q2W for 12 weeks (n = 6 active, 2 placebo).

[0752] Approximately 62 subjects will be enrolled in Part B to receive XTMAB-16 or placebo (1:1 ) in a randomized double-blind placebo-controlled manner for 24 weeks. Baseline dose of prednisone or equivalent will be used as a stratification factor during the randomization.

[0753] All subjects who have completed study participation in either Part A or B will be offered the opportunity to roll into an open label long-term safety study.

[0754] The subject population will be White (27; 69.2%) and not Hispanic or Latino (37; 94.9%). The average age of participants will be 54.3 years with a range of 33 to 71 years.

[0755] At Baseline, the average weight of participants at Baseline will be 95.6 kg with a range of 55.8 kg to 132.0 kg. The average systolic and diastolic blood pressure will be 129.4 mmhg and 79.0 mmhg, respectively. The average pulse will be 75.7 beats / min with a range of 53 to 107 beats / min.Summary of Key Eligibility Criteria: Inclusion Criteria1. Subject between 18 and 80 years (inclusive) of age.2. Weighs between 45 and 160 kg (99 to 353 lbs.) at Screening.3. Diagnosis of pulmonary sarcoidosis (at least 6 months before Screening) using the 2020 American Thoracic Society (ATS) Clinical Practice Guideline, the European Respiratory Society (ERS) or the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) criteria including a compatible clinical and radiologic presentation with other causes of granulomatous disease ruled out (cutaneous and ocular involvement permitted).4. Modified Medical Research Conference (mMRC) Dyspnea Scale of > 1.5. Receiving treatment of 7.5 to 25 mg / day of oral prednisone, or equivalent, during the screening period and, at the determination of the investigator, is capable of undergoing the protocol specific corticosteroid taper regimen.6. Receiving treatment with methotrexate, azathioprine, mycophenolate, leflunomide, chloroquine, or hydroxychloroquine for at least 3 months beforeScreening that has been at a stable dose for 4 weeks before Screening. All efforts should be made to maintain stable background therapy at the Screening dose through the intervention period at the Investigator’s discretion.7. PART A only: Willing to refrain from consumption of grapefruit or grapefruit juice [pomelos, exotic citrus fruits, or grapefruit hybrids] from screening visit until after the final dose.8. Polymerase chain reaction (PCR) test or rapid antigen test negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening.9. Able to provide written informed consent.10. In the opinion of the Investigator, the subject is capable of understanding and complying with protocol requirements.Summary of Key Eligibility Criteria: Exclusion Criteria1. Pregnant or breastfeeding women or women who are planning to become pregnant during the study.2. PART A ONLY: Subjects > 65 years of age.3. Known potentially significant fibrotic disease and / or active inflammation contained solely in the hilar region as shown by high-resolution computed tomography (HRCT), confirmed by a central reader. Subjects with current active inflammation in the hilar region with concurrent inflammation outside the hilar region may be included. For subjects with disease onset of < 2 years, a historical computed tomography (CT) within 6 months prior to screening confirmed by a central read is acceptable. For subjects with disease onset of > 2 years and without a CT within 6 months prior to screening, a CT will be performed at Screening.Note: For all subjects, regardless of their time of disease onset, if a historical HRCT is to be submitted for diagnosis confirmation, that HRCT must have been performed within 6 months of screening. If their last HRCT was from > 6 months prior to screening, then they will need to have an HRCT performed during screening for diagnosis confirmation.Note: Significant fibrotic disease is defined as > 20% fibrosis on HRCT.PART A ONLY: Any prior Tumor Necrosis Factor a (TNFa) inhibitor therapy. Clinically significant extra-pulmonary sarcoidosis requiring systemic therapy as determined by the investigator.PART B ONLY: Any therapy with an anti-TNFa monoclonal antibody (e.g., infliximab, adalimumab, golimumab and their biosimilars) within 6 months.Baseline percent predicted FVC of < 50%.Prior treatment with rituximab or repository corticotropin injection within the previous 12 months.Clinically significant Central Nervous System (CNS) sarcoidosis requiring therapy, except history of isolated seventh cranial nerve palsy or evidence of demyelinating neurologic disease.Advanced congestive heart failure (New York Heart Association [NYHA] 3 or 4). Current disease presentation consistent with Lofgren’s syndrome (i.e., presence of the triad of erythema nodosum, bilateral hilar lymphadenopathy on chest X-ray, and joint pain).Clinically significant pulmonary hypertension requiring treatment.Note: Clinically significant pulmonary hypertension requiring treatment would be defined as treatment with, i.e., prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists.Known hypersensitivity to any component of the formulation of XTMAB-16. Live or messenger ribonucleic acid (mRNA) vaccination within 2 weeks before Day 1 or inoculation with a live or mRNA vaccine is planned during study participation.Evidence of active or latent tuberculosis (TB) by interferon-gamma release assay (IGRA) or invasive fungal infections at Screening.Known positive history of malignancy other than non-melanomatous skin cancer in the last 2 years, including in-situ carcinoma of the uterine cervix completely cured by radical surgery.Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, coronavirus disease (COVID-19), TB, or a known history of human immunodeficiency virus (HIV) infection at Screening.Women of childbearing potential who are sexually active with a non-sterilized male partner and are not willing to adhere to adequate birth control measures from the time of signing the informed consent, throughout the duration of the study, and for 90 days after 5 half-lives have elapsed since the last dose of study drug.Male subjects who are non-sterilized and sexually active with a female partner of childbearing potential and are not willing to use adequate contraception from the time of signing the informed consent throughout the duration of the study, and for 90 days after 5 half-lives have elapsed since last dose of study drug. Clinically significant hepatic or renal disease, including uncontrolled diabetes at the discretion of the investigator.Any severe prior reaction to any type of biologies or human blood product such as albumin, immunoglobulin G (IgG) etc.Concurrent emphysema.Known hypercalcemia due to non-sarcoidosis conditions such as untreated hyperparathyroidism, at the discretion of the investigator.Abnormal electrocardiogram (ECG): ventricular arrhythmias (non-sustained ventricular tachycardia (VT), multifocal or frequent premature ventricular contractions, bundle branch block, axis deviation, or abnormal Q waves.). In the case of a QTcF (corrected QT interval by Fredericia) interval > 450 ms (men) or > 480 ms (women; subjects with bundle branch block) or PR interval outside the range of 120 to 220 ms, the assessment may be repeated once for eligibility determination at Screening or Baseline.Donation or loss of 450 mL or more of his or her blood volume (including plasmapheresis) or transfusion of any blood product within 90 days prior to dosing.Known uncontrolled hypertension.Note: Uncontrolled hypertension is noted as blood pressure > 160 / 100 mmHg despite antihypertensive therapy within 3 months of randomization.27. Clinical signs and symptoms consistent with COVID-19, e.g., fever, dry cough, dyspnea, sore throat, fatigue, new smell or taste disorder or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening.28. In the opinion of the investigator, inability to tolerate corticosteroid taper.29. Concurrent systemic steroid use for non-sarcoidosis conditions.30. Concurrent known auto-immune disease requiring treatment.31. Participation in another clinical trial of an investigational agent within 3 months (small molecule) I 6 months (biologies) or 5 half-lives (if known) of the agent, whichever is longer.32. Any condition that required hospitalization within the 3 months prior to Day 1 or is likely to require so during the study.33. Clinically significant abnormalities in the Screening physical exam, medical history, vital signs, ECG, or clinical laboratory tests that are not known to be due to concurrent sarcoidosis, and in the opinion of the Investigator and Medical Monitor should preclude the subject’s participation in the clinical study.Lifestyle Considerations:

[0756] During this study, subjects will be asked to:

[0757] 1. Refrain from consumption of red wine and Seville oranges from screening visit until after the final dose. In addition, subjects should also avoid consuming grapefruit or grapefruit juice (pomelos, exotic citrus fruits, or grapefruit hybrids) and any drug or diet that may interact with drug metabolizing enzymes activity from screening visit until after the final dose. This is essential as grapefruit enhances cortisol availability and will interfere with corticosteroid tapering essential for the study endpoint.

[0758] 2. Minimize interactions with household contacts who may be immunocompromised.

[0759] 3. Be vaccinated for COVID-19 at least 2 weeks prior to participation, defined as the initial 2-vaccine course of the Moderna or Pfizer vaccines, or a single J& J vaccine.Screen Failures

[0760] Screen failures are defined as subjects who consent to participate in the clinical trial but are not subsequently randomized or assigned to the study intervention or entered in the study.

[0761] A minimal set of screen failure information is required to ensure transparent reporting of screen failure subjects, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory authorities. Minimal information includes demographics, screen failure details, and eligibility criteria.

[0762] Individuals who do not meet the criteria for participation in this trial (screen failure) may be rescreened once at the discretion of the Investigator in consultation with the medical monitor. Rescreened subjects should be assigned the same subject number as for the initial screening.Treatment Failures

[0763] If the subject experiences the following, they will be considered a treatment failure:

[0764] 1. Addition of background second-line antimetabolite therapy. Note, antimetabolite therapy dose may be adjusted to avoid toxicity.

[0765] 2. Greater than 1 rescue period of corticosteroids.

[0766] 3. Breakthrough extrapulmonary disease requiring systemic treatment (topical and ophthalmic therapy for concurrent cutaneous and ocular disease are allowed).

[0767] 4. Inability to reach expected taper dose of 5 mg by Week 12.

[0768] 5. Inability to maintain taper dose or lower by Week 24 (Part B).

[0769] 6. Inability to taper steroids to targeted maintenance dose by Week 12 or Week 24 after rescue period.

[0770] 7. Rescue period requiring treatment longer than 2 weeks.

[0771] 8. Permanent drug discontinuation due to at least two Grade 3 or one Grade 4 toxicity considered by the Investigator to be associated with XTMAB-16 treatment (discontinuation of study drug will be considered treatment failure for analysis purposes).Study Intervention(s) and Concomitant Therapy

[0772] Study interventions will be conducted as outlined in Table 10:Table 10: Study Treatment Formulation and PreparationAbbreviations: IV = intravenous; mg = milligram; SWFI = sterile water for injection. Source: Pharmacy ManualDosing and Administration: Part A Dose Escalation:

[0773] During Part A, multiple doses and frequencies will be explored in an ascending fashion. To identify the recommended Phase 2 dose for Part B, the dose level groups will be enrolled both sequentially and in parallel by dose density as described below, and the cumulative safety data will be reviewed on an ongoing basis by the DSMC,

[0774] Part A will consist of 32 subjects in 4 cohorts of 8 subjects each, randomized in a 3:1 fashion (6 active, 2 placebo). First cohort at 2 mg / kg Q4W dose group will start enrolling the subjects initially. After the completion of a safety assessment of at least 4 subjects at this dose group who have completed 3 doses, it will be considered safe to proceed with dosing in the second and third cohort at 4 mg / kg Q4W and 2 mg / kg Q2W in parallel, as the dose density of these regimens are considered equal.

[0775] After the completion of a safety assessment of at least 4 subjects in both 4 mg / kg Q4W and 2 mg / kg Q2W dose groups (completion of 3 doses in the Q4W cohort and 6 doses of the Q2W cohort), it will be considered safe to proceed with dosing in the fourth cohort at 4 mg / kg Q2W.

[0776] The DSMC may make independent decisions about the safety of both 4 mg / kg Q4W and 2 mg / kg Q2W dose groups in the second and third cohort to decide if it is safe to go to the next dose group.

[0777] The escalation scheme will be conducted according to the schema illustrated in FIG. 4.

[0778] Enrollment will not pause between cohorts unless the minimum follow-up in a cohort has not been achieved and will enroll continuously while regular safety reviews occur. Following regular safety data reviews, at the discretion of the DSMC, dose escalation and enrollment in all dose groups may be paused for a complete safety evaluation if any safety signals or DLTs are identified. Criteria for a DLT are as follows: any prolonged Grade 2 (defined as continuous at Grade 2 (or higher) for more than 3weeks) or any Grade 3 or higher adverse event that is considered related to study drug and is not attributable to worsening of concurrent illness.

[0779] Stopping criteria for a safety signal that may warrant the DSMC to request additional safety review during the dose escalation phase are as follows:

[0780] 1. Any SAE assessed as related to study drug

[0781] 2. Any signs of serious infection such as TB, bacterial sepsis or invasive fungal infection, or lymphoma diagnosis

[0782] 3. Grade 3 hypersensitivity or anaphylaxis

[0783] The completion of extended DSMC safety review may result in resuming enrollment, proceeding with dose escalation, expanding the current dose level cohort, or terminating enrollment. Dose escalation will continue in this manner until the highest planned dose level is complete or a DSMC decision to discontinue enrollment due to safety. An unscheduled PK sample, ECG or clinical laboratory data analysis may be performed to support the safety assessment, if needed, in the event of a safety signal of concern.Dose Selection: Part B (POC)

[0784] At the completion and review of data by the DSMC from Part A of this study, a dose level and frequency will be determined for the Part B POC portion of the study. Dose determination will be guided by observed meaningful relevant PK parameters (Ctrough, AUC), observed relationship of PK and in vitro measures of pharmacologic activity, observed change in clinically meaningful biomarkers (ACE, sIL 2R, CRP, IL-1b), observed clinical benefit (ability to reduce background oral corticosteroid use, change in QoL and Pulmonary endpoints), and observed safety signals and DLTs per cohort. An exploratory efficacy and / or PK data analysis may be performed to select the recommended Phase 2 dose for Part B, if needed.Oral Corticosteroid Taper Protocol: Part A (MAD)

[0785] During Part A of the study, two weeks after completion of the first dose and prior to the second administered dose for subjects assigned to Q2W dosing schedule, subjects will begin tapering corticosteroids from their starting dose to a target dose of 5 mg / day of prednisone, or equivalent, or less, to be completed on or before Week 12. The corticosteroid will be tapered depending on the starting dose as shown in Table 39.The subject’s corticosteroid dosage may be further titrated below 5 mg / day or discontinued when feasible.

[0786] In cases where the subject has had > 5% absolute worsening of FVC% (at 2 visits at least 7 days apart), subjects may have their oral corticosteroid dose increased at the investigator’s discretion during the rescue therapy period of two weeks. Symptomatic flare will be confirmed by a change of score by > 4-point fall of King’s Sarcoidosis Questionnaire Lung Module (KSQ-Lung) and / or a decrease in Leicester Cough Questionnaire (LCQ) score by > 1 point, or the investigator determines a rescue dose of corticosteroids is warranted due to worsening cough, shortness of breath, exercise intolerance, or worsening symptoms. Subjects should be evaluated in clinic when possible or via telehealth.

[0787] If an increase in steroid dose is not clinically indicated, steroid rescue therapy is not mandated in the event of worsening cough or worsening dyspnea or change in FVC. Subjects who require an increase in their steroid dose at any time in the study should continue to receive study drug and follow through to the end of the study. Subject will document steroid doses in a diary, which will be reviewed at scheduled telephone contacts and site visits.

[0788] For subjects who require a corticosteroid rescue therapy between Baseline and Week 12, a taper may continue after the acute event resolves at the investigator’s discretion. The steroid taper must be completed by Week 12, regardless of rescue therapy, to be considered a treatment success. Inability to taper after rescue therapy will constitute a treatment failure. Subjects will be allowed up to one corticosteroid rescue therapy between Baseline and Week 12 to be considered responsive to treatment, however, subjects may be given additional corticosteroid rescue therapy if determined necessary by the Investigator.Table 11: Corticosteroid Taper Protocol by Start Dose Part A (MAD)Abbreviations: MAD = multiple ascending dose; mg = milligram.A The doses reflected in the table are prednisone doses.Oral Corticosteroid Taper Protocol: Part B (POC)

[0789] During Part B of the study, two weeks after completion of the first dose and prior to the second administered, subjects will begin tapering corticosteroids from their starting dose to a target dose of 5 mg / day of prednisone, or equivalent, or less, to be completed on or before Week 12 and maintained through Week 24 (Table 12). The corticosteroid will be tapered depending on the starting dose, and at the investigator’s discretion. At the investigator’s discretion, subject’s corticosteroid dosage may be further titrated below 5 mg / day or discontinued when feasible.

[0790] In cases where the subject has had >5% absolute worsening of FVC% (at 2 visits at least 7 days apart), subjects may have their corticosteroid dose increased at the investigator’s discretion during the rescue therapy period of two weeks. Symptomatic flare will be confirmed by a change of score by > 4-point fall of KSQ-Lung and / or a decrease in LCQ score by > 1 point, or the investigator determines a rescue dose of corticosteroids is warranted due to worsening cough, shortness of breath, exercise intolerance, or worsening symptoms. Subjects should be evaluated in clinic or via telehealth.

[0791] If an increase in steroid dose is not clinically indicated, steroid rescue therapy is not mandated in the event of worsening cough or worsening dyspnea or change in FVC. Subjects who require an increase in their steroid dose at any time in the study should continue to receive blinded investigational product and follow through to the end of the study. Subjects will document steroid doses in a diary, which will be reviewed at relevant scheduled telephone contacts and site visits.

[0792] For subjects who require a corticosteroid rescue therapy between Baseline and Week 12, a taper may continue after the acute event resolves at the investigator’sdiscretion. The steroid taper must be completed by Week 12 and maintained through Week 24, regardless of rescue therapy, to be considered a treatment success. Inability to taper after rescue therapy will constitute a treatment failure. Subjects will be allowed up to one corticosteroid rescue therapy to be considered responsive to treatment, however, subjects may be given additional corticosteroid rescue therapy if determined necessary.Table 12: Corticosteroid Taper Protocol by Start Dose Part B (POC)Abbreviations: mg = milligram; POC = proof of concept.A The doses reflected in the table are prednisone doses.Formulation of XTMAB-16

[0793] The XTMAB-16 for injection (drug product) manufacturing process is comprised of formulation, filtration, fill, semi stoppering, lyophilization, full-stoppering, and seal steps. The drug product is sterilized by filtration prior to aseptic filling. No impurities are introduced during drug product manufacturing.

[0794] The lyophilized drug product, XTMAB-16, is supplied as a sterile, white to off-white, lyophilized powder or lyophilized cake (100 mg XTMAB-16 per vial) in 20 mL vial for reconstitution with 10 mL of sterile water for injection (SWFI) and IV infusion. The reconstituted solution concentration is 10 mg / mL. With a pH of 5.8 to 6.2. The reconstituted solution is diluted with sterile 0.9% sodium chloride injection, United States Pharmacopeia (USP) to the range between 0.4 mg / mL and 4 mg / mL for infusion.

[0795] The matching placebo has the same formulation as the drug product except it contains no XTMAB-16.Randomization and Blinding

[0796] In both Part A (MAD) and Part B (POC) of this study, subjects will be randomly assigned to treatment (XTMAB-16 or placebo) and treatment assignment will be double-blind; all study staff will be blind to subject treatment assignment for the duration of the study. The infusion solution containing active drug and placebo will be indistinguishable in appearance. All study assessments and causality will be performed, if possible, prior to unblinding.Prior and Concomitant Therapy

[0797] Prior medication history for up to a year before screening will be collected. The use of concomitant medication is allowed during the study unless specified in the inclusion or exclusion criteria or study procedures. The name of the medication, indication, dose, and duration of use will be recorded on the eCRF. If a new concomitant therapy is started due to an adverse event, the adverse event must be recorded on the eCRF.

[0798] Concomitant corticosteroid dose will be self-recorded in a subject diary and verified by site personnel at each in person or telephone visit.

[0799] Subjects will receive concomitant treatment with methotrexate, azathioprine, mycophenolate, leflunomide, chloroquine, or hydroxychloroquine for at least 3 months before screening that has been at a stable dose for 4 weeks before screening. All efforts should be made to maintain stable background therapy at the screening dose through the intervention period.

[0800] Subjects will also receive treatment with 7.5 to 25 mg / day of oral prednisone, or equivalent, during the screening period, which will be weaned during the duration of the study period.Study Assessments and Procedures: Efficacy Assessments

[0801] Planned time points for all efficacy assessments are provided in the SoA. Study Assessments and Procedures: Quality of Life Measures

[0802] All Quality of Life assessments are to be performed before other study procedures at each designated visit and are to be completed in the same order at each designated visit. The order of Quality of Life Measurements will be outlined in the electronic Clinical Outcome Assessments (eCOA) Site Manual.Study Assessments and Procedures: King’s Sarcoidosis Questionnaire

[0803] The King’s Sarcoidosis Questionnaire (KSQ) is an online 29-item questionnaire to be completed by sarcoidosis subjects. The KSQ is split into 5 sections: general health status, lungs, medication, skin, and eyes. Results are given as a number between 1 to 100 with higher numbers indicating better health. The questionnaire takes approximately 10 minutes to complete. The minimal clinically important difference (MCID) for KSQ remains unclear in sarcoidosis.Study Assessments and Procedures: Leicester Cough Questionnaire

[0804] The Leicester Cough Questionnaire (LCQ) is a 19-item self-completed quality of life measure of chronic cough which is responsive to change. Items on the scale are divided into 3 domains, physical, psychological, and social. Items are scored on a 7-point Likert scale. A total score (range 3 to 21) is also calculated by adding the domain scores together, with higher scores indicating better quality of life. The questionnaire takes 5 to 10 minutes to complete. The MCID for chronic cough is 1.3. Study Assessments and Procedures: Short Form-36

[0805] The Short Form-36 (SF-36) is a 36-item, subject-reported survey of subject health. The SF-36 includes one multi-item scale that assesses eight health concepts: 1 ) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Study Assessments and Procedures: Fatigue Assessment Scale

[0806] The Fatigue Assessment Scale (FAS) contains 10 specific fatigue questions that have been validated in sarcoidosis subjects. On each question, one of 5 answer categories may be chosen, from never to always: 1 = never; 2 = sometimes (about monthly or less); 3 = regularly (about a few times a month); 4 = often (aboutweekly); 5 = always (about every day). An answer to each question has to be given, even if the person does not have any complaints at the moment. Scores on questions 4 and 10 should be recoded (1 = 5, 2 = 4, 3 = 3, 4 = 2, 5 = 1). Subsequently, the total FAS score may be calculated by summing the scores on all questions (the recoded scores for question 4 and 10). The sum of questions 3 and 6 to 9 indicates mental fatigue, and the sum of the questions 1, 2, 4, 5 and 10 indicates physical fatigue. The minimal score is 10, and the maximal score is 50. Scores of > 22 are considered to represent substantial fatigue. A change in the FAS score of 4 points is considered to be the MCID. The FAS takes approximately 5 to 10 minutes to complete.Study Assessments and Procedures: Patient Global Assessment

[0807] The patient global assessment (PGA) is a subject-reported outcome instrument used to gauge the subject’s well-being and is scored using a visual analogue scale (VAS). The MCID in sarcoidosis remains unclear in randomized controlled trials. A previously reported MCID for PGA in sarcoidosis was < 7 cm, 7 to 10 cm.Study Assessments and Procedures: Steroid Toxicity Questionnaire

[0808] Glucocorticoids (GCs) are associated with clinically important toxicities in sarcoidosis subjects, associated with both the cumulative dose and duration of treatment. The Steroid Toxicity Questionnaire (STQ) is a simple 12 question tool used to characterize the toxicity associated with steroid use using a 4-point scale. The MCID remains unclear in sarcoidosis.Study Assessments and Procedures: Modified Medical Research Council Dyspnea Scale

[0809] The modified Medical Research Council (mMRC) Dyspnea Scale is a five-level rating scale based on the subject’s perception of dyspnea in daily activities, ranging from none (Grade 0) to very severe dyspnea (Grade 4). The score is the number that best fits the subject’s level of activity.Study Assessments and Procedures: Pulmonary Function Tests

[0810] Pulmonary function tests (PFTs), including FVC, forced expiratory volume in 1 second (FEV1), and FEV1 / FVC ratio, are to be determined by spirometry at the time points designated in SoA. Spirometry testing will be performed according to the ATS / ERS guidelines. The spirometer (SpiroSphere) and associated equipment besupplied to each site for the study. The same spirometry equipment must be used for all assessments performed for a subject. All subjects at all visits will be evaluated throughout the entire trial. Where possible the same technician should perform all maneuvers for an individual subject. All staff conducting the spirometry tests must have received appropriate training and pass two proficiency tests which must be documented. Spirometry ideally is to be performed with the subject in a seated position for at least 2 minutes with a tight seal around the mouth and wearing nose-clips or manual occlusion of the nostrils; the subject is to remain seated with head slightly elevated throughout the test procedure. If the testing is undertaken with the subject in another position, this must be documented in the report. It is recommended that the test be performed at least 1 hour after a light meal, avoid smoking and / or vaping and / or water pipe use within 1 hour before testing, avoid consuming intoxicants within 8 hours before testing, avoid wearing clothing that substantially restricts full chest and abdominal expansion and refrain from vigorous exercise within 1 hour of testing. If treated with bronchodilators, subjects should withhold medications prior to spirometry according to guidelines listed in Table 13. Spirometry is to be performed in the same manner across all assessment time points.Table 13: Guidelines for Withholding Bronchodilator MedicationsAbbreviations: LABA = long-acting 02 agonists; LAMA = long-acting muscarinic antagonists; SABA = short acting 2 agonists; SAMA = short-acting muscarinic antagonists.Study Assessments and Procedures: 6 Minute Walk Distance

[0811] The 6-minute walk distance (6MWD) will record the distance walked in six minutes, the level of oxygenation using a pulse oximeter and the level of dyspnea using a ten point dyspnea scale (Borg score). A standardized protocol for the six-minute walk will be done for all sites and must be performed in the same manner across all timepoints.Study Assessments and Procedures: High-resolution computed tomography

[0812] High-resolution computed tomography (HRCT) is the modality of choice for evaluating the features of thoracic sarcoidosis. It depicts the characteristic features of the parenchymal nodules and lesions, their distribution, the associated changes, and atypical features accurately. It also helps in guiding the appropriate therapy by differentiating active lesions from irreversible fibrosis.Safety and Other Assessments

[0813] Planned timepoints for all safety and other assessments are provided in the SoA (Table 44-Table 51).Safety and Other Assessments: Physical Examination

[0814] A complete physical examination will include assessments of general appearance, skin; head / neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary (optional), lymphatic, and musculoskeletal systems; extremities; eyes (inspection and vision control); nose; throat; and neurologic status. An abbreviated physical examination will include assessments of general appearance; head, ears, eyes, nose, and throat; cardiovascular; respiratory; and gastrointestinal systems (including the abdomen). A targeted physical examination may be conducted at any time at the Investigator’s discretion and should be limited to systems of clinical relevance (i.e., cardiovascular, respiratory, lymph nodes, liver).Safety and Other Assessments: Height and Weight

[0815] Height (cm) will be measured only at Screening. Weight will be measured in kilograms at every visit according to the SoA.Safety and Other Assessments: Vital Signs

[0816] Oral, tympanic, or temporal body temperature, respiratory rate, pulse, and systolic and diastolic blood pressure (BP) will be assessed. The method of bodytemperature assessment chosen should be recorded and consistent throughout the study. If oral temperatures (°C) are taken, subjects will have had no recent hot or cold beverages or smoking.

[0817] During the infusion, systolic / diastolic blood pressure and pulse should be measured in a semi-supine / semi-reclined position. For all other readings, blood pressure and pulse will be taken in a supine position after 10 to 15 minutes rest. During the infusion, vital signs should be collected per the study site’s standard of care intervals.

[0818] Respiratory rate (breaths / min) will be taken after at least 5 minutes rest; breaths are counted for 30 seconds and multiplied by 2. Respiration rate will be taken once during the ECG. During the infusion, respiration rate will be taken in a semi-supine / semi-reclined position.Safety and Other Assessments: Electrocardiograms

[0819] Standard 12-lead ECGs will be recorded as the subject has been resting in the supine position for at least 10 minutes. ECGs will be collected in triplicate at the timepoints noted the SoA (Table 44-Table 51) with approximately 1 minute between each ECG; all other ECGs will be collected as single recordings. Additional ECGs will be performed at the discretion of the Investigator.

[0820] The Investigator will be responsible for reviewing the ECG to assess whether the ECG is within the reference limits and to determine clinical significance of the results. If necessary, the Investigator has the right to override the interpretation and intervals as measured by the ECG machine. Respiration rate will be taken once during the ECG. The ECG will be assessed for the following measures: P wave, QRS complex, U wave, QRS duration, QT interval, T wave, ST segment, RR interval, PR interval, and qualitative results.Safety and Other Assessments: Clinical Laboratory Evaluation

[0821] Clinical laboratory assessments will be collected under appropriate conditions defined by the clinical unit’s standard of practice at the time points specified in the SoA.

[0822] The central lab will be used to perform all clinical laboratory tests excluding urine pregnancy dipstick, which will be assessed by the site staff. The Investigator should take immediate action for any safety concerns based on laboratory results.

[0823] Record any clinically relevant changes occurring during the study in the EDC system. The laboratory reports must be filed with the source documents. Clinically significant abnormal laboratory findings are those that are not associated with an underlying disease, unless judged by the Investigator to be more severe than expected for the subject’s condition.

[0824] All laboratory tests with values considered clinically significantly abnormal during participation in the study, including the subject’s last EOS visit, should be repeated until the values return to normal or Baseline or are no longer considered clinically significant or follow-up is no longer needed per the judgment of the Investigator or Medical Monitor.

[0825] If such values do not return to normal / Baseline within a period of time judged reasonable by the Investigator, the etiology should be identified, and the Sponsor notified.Safety and Other Assessments: Computed Tomography Scan

[0826] Images of the Computed Tomography (CT) scan will be centrally read and assessed by a three -point Likert scale (worse to better) by the central reader.Pharmacokinetics

[0827] Whole blood samples will be collected for measurement of serum concentrations of XTMAB-16. Instructions for the collection and handling of biological samples will be provided by the Sponsor in a separate laboratory manual. The actual date and time (24-hour clock) of each sample will be recorded in the eCRF. Samples will be used to evaluate the serum concentration and PK of XTMAB-16. Each serum sample will be divided into 2 aliquots (1 each for primary and back-up).

[0828] Measurement of concentrations of XTMAB-16 will be performed using a validated assay method under the supervision of the Sponsor or qualified designee. The analytical methods used to measure concentrations of XTMAB-16 will be described in a separate bioanalytical report. Only samples that are within the window of sample stability will be analyzed

[0829] While PK samples must be collected from subjects assigned to the placebo arm to maintain the blinding of treatment assignment, PK assay results for these subjects are not needed for the safety conduct or proper interpretation of this trial and most samples will therefore not be analyzed. Personnel responsible for performing PK analysis will be unblinded to subjects’ treatment assignments to identify appropriate PK samples to be analyzed. Samples from subjects assigned to placebo may be analyzed upon request (i.e., to evaluate a possible error in dosing).

[0830] Any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal or investigational product, whether or not related to the medicinal or investigational product.Clinical Laboratory Tests

[0831] Additional tests may be performed at any time during the study. Nonlimiting examples of such are outlined in Table 14.Table 14: Clinical Laboratory ParametersAbbreviations: HIV = human immunodeficiency virus; SoA = schedule of activities; WOCBP = women of childbearing potential.a Tryptase will be assessed only at Baseline (for all subjects) and in the event a subject experiences anaphylaxis within 4 hours after end of infusion (sample to be collected as soon as is reasonable after treatment).Adverse Event of Special Interest (AES I)

[0832] An AE (serious or non-serious) of scientific and medical concern specific to the Sponsor’s study drug or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor may be appropriate. An AESI might require further investigation in order to characterize and understand it. Depending on the nature of the AESI, rapid communication between the Sponsor and Regulatory Authorities might also be warranted.Biomarkers

[0833] Whole blood samples will be collected for measurement of exploratory circulating biomarkers according to Table 60. Instructions for the collection and handling of biological samples will be provided by the Sponsor in a separate laboratory manual. The actual date and time (24-hour clock time) of each sample will be recorded in the eCRF. Data collected from analyses of circulating biomarkers may be used to correlate exposure to safety or efficacy aspects related to concerns arising during or after the study.

[0834] Measurement of circulating biomarkers will be performed using a fit-for-purpose qualified assay method under the supervision of the Sponsor or qualified designee. The analytical methods used to measure these biomarker endpoints will be described in separate bioanalytical reports. Only samples that are within the window of sample stability will be analyzed.

[0835] Circulating biomarkers that will be evaluated include ACE, interleukin-6 (IL-6), sIL 2R, soluble tumor necrosis factor a (sTNFa), C- reactive protein (CRP), calcitrioland IL-1 b. ACE is a common biomarker used in the diagnosis of sarcoidosis. sIL 2R, a surrogate marker for T cell activation, may be elevated in some sarcoidosis subjects, and has been shown to have a high and superior sensitivity and specificity, compared to ACE, for diagnosing sarcoidosis in subjects. IL-6 is commonly elevated in subjects with sarcoidosis and may be involved in the initiation and maintenance of alveolitis by activating and causing the proliferation of T cells. TNFa induces IL-6 through the nuclear factor k B pathway and, thus, inhibition of TNFa through XTMAB-16 is likely to be reflected in a change in IL-6 circulating levels. Acute tissue injury in the lung, initiated by IL-1 b converts to fibrotic changes. IL-1 b may be a target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling, like sarcoidosis.Immunogenicity

[0836] Antibodies to XTMAB-16 will be evaluated in serum samples collected from all subjects according to Table 9. Additionally, serum samples should also be collected at safety follow-up visits from subjects who discontinue from the study or choose to not rollover into the long term open label safety study. Persistence of ADA status will be measured as defined below.

[0837] Transient ADA response:

[0838] (i) T reatment-induced ADA detected only at one sampling time point during the treatment or follow-up observation period (excluding the last sampling time point, which ought to be considered persistent unless shown to be undetectable at a later time), or

[0839] (ii) Treatment-induced ADA detected at two or more sampling time points during the treatment (including follow-up period if any), where the first and last ADApositive samples (irrespective of any negative samples in between) are separated by a period less than 16 weeks, and the subject’s last sampling time point is ADA-negative.

[0840] Persistent ADA response:

[0841] (i) Treatment-induced ADA detected at two or more sampling time points during the treatment (including follow-up period if any), where the first and last ADApositive samples (irrespective of any negative samples in between) are separated by a period of 16 weeks or longer, or

[0842] (ii) Treatment-induced ADA incidence only in the last sampling time point of the treatment study period or at a sampling time point with less than 16 weeks before an ADA-negative last sample.

[0843] Instructions for the collection and handling of biological samples will be provided by the Sponsor in a separate laboratory manual. These samples will be tested by the Sponsor or Sponsor’s designee. Each serum sample will be divided into 2 aliquots (1 each for primary and a back-up).

[0844] Serum samples will be tested in a multi-tiered approach. A validated screening assay for antibodies binding to XTMAB-16 will be initially used to assess serum samples. Samples that are determined putative positive for ADA in the screening assay will then be subjected to a confirmatory assay to demonstrate that antibodies are specific to XTMAB-16. Samples that are identified as positive in the confirmatory assay will be further characterized in a validated tier assay and titer of confirmed positive samples will be reported. Other analyses may be performed to verify the stability of antibodies to study treatment and / or to further characterize the immunogenicity of study treatment. Serum samples will be screened for antibodies binding to XTMAB-16 and the titer of confirmed positive samples will be reported.

[0845] The detection and characterization of antibodies to XTMAB-16 will be performed using a validated assay method under the supervision of the Sponsor or qualified designee. The analytical methods used to measure immunogenicity will be described in a separate bioanalytical report. Only samples which are within the window of sample stability will be analyzed.

[0846] Samples that are confirmed positive for antibodies binding to XTMAB-16 with a positive titer may be further characterized and / or evaluated for their ability to neutralize the activity of the study treatment using a validated assay method.Summary of Statistical Considerations

[0847] Summary statistics for continuous variables will consist of number of nonmissing observations (n), mean, standard deviation (SD), minimum, median, and maximum, unless specified otherwise. For categorical variables, the number and percentage of subjects in each category will be presented. When appropriate, 95%confidence intervals (Cl) will be provided. Primary analysis set for Part A is SAS and for Part B is FAS, unless specified otherwise.

[0848] The data will be summarized in tabular form by treatment group combined across cohort in Part A and by treatment group in Part B. In Part A the 2 placebo subjects in each cohort will be combined into a placebo group of 8 subjects.

[0849] Baseline will be defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study treatment.

[0850] Baseline for corticosteroid (prednisone or equivalent) dose will be the dosing value established at the time of receiving the study treatment on day 1.General Calculation or Derivation of Efficacy Variables

[0851] Percentage Reduction from Baseline in Prednisone Dose:

[0852] The percentage reduction from baseline in prednisone, or equivalent, dose for a given timepoint, defined as: {(Baseline dose- timepoint dose) / baseline dose} *100%

[0853] Proportion of Subjects with Prednisone Dose < 5 mg / day:

[0854] For each treatment group for a particular timepoint, the number of subjects with prednisone, or equivalent, dose <5 mg / day will be calculated. The proportion of such subjects will be calculated for each treatment group for a given timepoint as: (Number of subjects with prednisone, or equivalent, dose < 5 mg / day at given timepoint / number of subjects in treatment group)

[0855] Proportion of Subjects with > 50% Reduction from Baseline in the Prednisone Dose:

[0856] For an individual subject, if the above calculation results in a value of 50% or greater, that subject will be classified as having at least a 50% reduction in daily prednisone, or equivalent, dose. The proportion of such subjects will be calculated for each treatment group as: (Number of subjects with > 50% reduction at given timepoint / number of subjects in treatment group).Analysis of the Primary Endpoints: Part A (MAD)

[0857] There is no primary efficacy endpoint for Part A of the study.

[0858] To observe the primary safety endpoint, the frequencies of treatment-emergent adverse events (TEAEs) and the number of subjects with TEAEs will be summarized overall and for applicable categories (e.g., seriousness, treatment-related, severity) by treatment group across cohorts in Part A in the SAS population. Observed DLT, rate of AESI will also be summarized by dose levels and frequencies.

[0859] PK, PD, ADA, reduction in dose of corticosteroid, QoL and pulmonary data will be observed and summarized descriptively to determine the recommended Phase 2 dose for Part B.

[0860] For PK endpoint, plasma concentrations of XTMAB-16 will be summarized in tabular form for at least minimal key PK parameters of interest (Ctrough and AUC over the dosing interval). PK methods and the analysis will be described in a standalone PK analysis plan

[0861] For PD endpoint, biomarkers at each biomarker sampling time point will be summarized with absolute and percentage change descriptively for ACE, sIL 2R, GRP, IL-1 b and Calcitriol.

[0862] Reduction in dose of corticosteroid will be summarized with absolute and percentage change descriptively over the time.

[0863] Quality of life and pulmonary data will be summarized with absolute and percentage change descriptively over the time from baseline for mean percent change in FVC%, KSQ General, KSQ-L scores, LSQ and STQ scores.Analysis of the Primary Endpoints: Part B (POC)

[0864] For the primary efficacy endpoint [targeted tapered dose of corticosteroid (maximum dose of prednisone 5 mg / day or equivalent) responders] for Part B of the study, a 1 -sided 95% confidence interval (Cl) approach for the difference of proportion of subjects having targeted tapered dose of corticosteroid (using the point estimate of the difference between XTMAB-16 vs Placebo) by Week 12 will be used to test for the superiority of XTMAB-16 in the FAS population. The proportion and their 95% Cl using Clopper-Pearson test will also be displayed. Cochran Mantel Haenszel test (CMH) stratified for the stratification factor (baseline dose of prednisone or equivalent) will also be performed. This analysis will be performed on FAS population.

[0865] The categories of response are defined as follows:

[0866] Responder: For subjects who require a corticosteroid rescue therapy between Baseline and Week 12, a taper may continue after the acute event resolves at the investigator’s discretion. The steroid taper must be completed by Week 12 regardless of corticosteroid rescue therapy, to be considered as a responder.

[0867] Non-Responder: Inability to taper after rescue therapy by Week 12 will be considered as a non-responder.Estimand Framework

[0868] An addendum to International Council for Harmonization (ICH) E9 (R1) introduces the concept of an estimand which translates the trial objective into a precise definition of the treatment effect that is to be estimated. For Part B primary endpoint, the description of the estimand includes four attributes: the population, the variable (or endpoint) to be obtained for each subject, the specification of how to account for intercurrent events (ICE) and the population-level summary for the variable. These attributes are described in Table 15.Table 15: Estimand Framework

[0869] The categories of response in Estimand framework are defined as follows:

[0870] Responder: For subjects who require a corticosteroid rescue therapy between Baseline and Week 12, a taper may continue after the acute event resolves at the investigator’s discretion. The steroid taper must be completed by Week 12 regardless of corticosteroid rescue therapy, to be considered as a responder.

[0871] Non-Responders: Inability to steroid taper by Week 12 will be considered as a non-responder, if the subjects have the following events reported:

[0872] i. Receipt of more than one corticosteroid rescue therapy

[0873] ii. Extrapulmonary disease requiring systemic treatment other than topical cutaneous and ophthalmic treatment

[0874] Hi. Addition of background sarcoidosis concomitant medications noted in Inclusion criterion 6

[0875] iv. Discontinuation of study drug due to any reasonAnalysis of the Secondary Endpoint(s): Part A (MAD)

[0876] Part A will be summarized for Efficacy, PK, Biomarker and Immunogenicity secondary endpoints.

[0877] (i) Efficacy:

[0878] Number and proportion of subjects who achieve the targeted tapered dose of corticosteroid (maximum dose of prednisone 5 mg / day or equivalent) and subjects who achieve at least 50% reduction in dose of corticosteroid by Week 12 will be summarized by treatment group and by combining active treatment groups in Part A. The proportion and their 95% Cl using Clopper-Pearson test will also be displayed.

[0879] Absolute and change from baseline for reduction in dose of corticosteroid will also be summarized descriptively over the time by treatment group and by combining active treatment groups in Part A.

[0880] The efficacy analysis will be performed on FAS population.

[0881] (ii) Pharmacokinetics:

[0882] Plasma concentrations of XTMAB-16 will be analyzed by either noncompartmental and / or population PK methods and the analysis will be described in a standalone PK analysis plan. At a minimum, key PK parameters of interest (Ctroughand AUC over the dosing interval) will be estimated and descriptively summarized. Additional evaluations may include an assessment of dose proportionality and estimated time to achieve steady-state.

[0883] Consideration of stratification by key covariates of interested (e.g., ADA confirmed positive status) may be performed as data permits.

[0884] (iii) Biomarker:

[0885] Biomarkers at each biomarker sampling time point will be summarized with descriptive statistics (N, mean, SD, coefficient of variation (CV)%, geometric mean, geometric CV%, median, minimum, and maximum) and listed over the time by treatment group. Biomarker-Time Profile plots for individual and combined mean (+ / - SD) will be generated as appropriate.

[0886] Absolute and percent change in biomarkers from Baseline to EOI, Week 2, 4, 8, and 12 for the following parameters: IL-6, sTNFa.

[0887] (iv) Immunogenicity:

[0888] Anti-drug antibodies and nAb at each sampling time point will be summarized with descriptive statistics (N, mean, SD, GV, geometric mean, geometric GV, median, minimum, and maximum) by treatment group.

[0889] Number and percentage of subjects who test positive for XTMAB-16 ADA at Baseline, Week 4, Week 8, and Week 12 and number and percentage who test positive for XTMAB-16 nAb at Baseline, Week 4, Week 8, and Week 12 by treatment group will be displayed. The transient and persistent positive status will also be summarized by number and percentages for follow-up assessments.Analysis of the Secondary Endpoint(s): Part B (POO)

[0890] Part B will be summarized for Safety, Efficacy, PK, Biomarker and Immunogenicity secondary endpoints.

[0891] (i) Efficacy:

[0892] Statistical analysis for difference in proportion of subjects who achieve at least 50% reduction by Week 12 and difference in proportion of subjects able to maintain steroid reduction at Week 24 will be performed similar to primary endpoint analysis forPart B by treatment group. The proportion and their 95% Cl using Clopper-Pearson test will also be displayed.

[0893] Absolute and change from baseline for reduction in dose of corticosteroid will also be summarized descriptively over the time. Number and percentage for targeted tapered dose of corticosteroid (maximum prednisone 5 mg / day or equivalent) over the timepoint 12 weeks onwards will also be summarized by treatment group.

[0894] The analysis will be performed on FAS population.

[0895] A sensitivity analysis may be performed excluding treatment discontinuation before 12-week taper assessment for primary efficacy endpoint.

[0896] (ii) Pharmacokinetics:

[0897] Plasma concentrations of XTMAB-16 will be analyzed by either noncompartmental and / or population PK methods and the analysis will be described in a standalone PK analysis plan. At a minimum, key PK parameters of interest (Ctrough and AUC over the dosing interval) will be estimated and descriptively summarized. Additional evaluations may include an assessment of dose proportionality and estimated time to achieve steady-state.

[0898] Consideration of stratification by key covariates of interested (e.g., ADA confirmed positive status) may be performed as data permits.

[0899] (iii) Biomarker:

[0900] Biomarkers at each biomarker sampling time point will be summarized with descriptive statistics (N, mean, SD, CV%, geometric mean, geometric CV%, median, minimum, and maximum) and listed over the time. Biomarker-Time Profile plots for individual and combined mean (± SD) will be generated as appropriate.

[0901] Absolute and percent change in biomarkers from Baseline to Week 12 and Week 24 for the following parameters: ACE, IL-6, sIL 2R, sTNFct, CRP, Calcitriol (vitamin D 1, 25), IL-1 b.

[0902] (iv) Immunogenicity:

[0903] Anti-drug antibodies and nAb at each sampling time point will be summarized with descriptive statistics (N, mean, SD, CV, geometric mean, geometric CV, median, minimum, and maximum).

[0904] Number and percentage of subjects who test positive for XTMAB-16 ADA at Baseline to Week 24 and number and c...

Claims

1. CLAIMS2.I / We claim:

1. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time.

2. A method of reducing or tapering concurrent corticosteriod use in a subject with sarcoidosis relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time.

3. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

4. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6),and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

5. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

6. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises9.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;10.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;11.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;12.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;13.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;14.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;15.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;16.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;17.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;18.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

7. A method of reducing or tapering concurrent corticosteriod use in a subject with sarcoidosis relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises20.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;21.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;22.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;23.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;24.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;25.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;26.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;27.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;28.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;29.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

8. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a quality of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ), a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises31.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;32.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4; (iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;33.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;34.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;35.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;36.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;37.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;38.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;39.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;40.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

9. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;42.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;43.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;44.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;45.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;46.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;47.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;48.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;49.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;50.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;51.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

10. A method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, the method comprising administering to the subject a dose of about 2 mg / kg or 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the compositionimproves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises53.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;54.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;55.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;56.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;57.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;58.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;59.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;60.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;61.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;62.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;63.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

15.

11. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks.

12. A method of reducing or tapering concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks.

13. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to a control or baseline.

14. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline.

15. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylatedwith one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

16. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises69.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;70.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;71.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;72.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;73.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;74.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;75.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;76.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;77.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;78.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

17. A method of reducing or tapering concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises80.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;81.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;82.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;83.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;84.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;85.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;86.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;87.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;88.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;89.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

18. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises91.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;92.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;93.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;94.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;95.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;96.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8; (vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;97.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;98.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;99.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;100.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

19. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises102.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;103.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;104.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;105.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;106.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;107.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;108.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;109.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;110.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;111.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

20. A method of treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, the method comprising administering to the subject a dose of about 4 mg / kg of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline and wherein the anti-TNFa antibody comprises113.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;114.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;115.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;116.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;117.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;118.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;119.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;120.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;121.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;122.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

21. The method of any one of claims 1 -10, wherein the dose is about 2 mg / kg of the composition.

22. The method of any one of claims 1 -10, wherein the dose is about 4 mg / kg of the composition.

23. The method of any one of claims 1-10, wherein the method comprises administering to the subject about 2 mg / kg of the composition once every 2 weeks for the first period of time.

24. The method of any one of claims 1-10, wherein the method comprises administering to the subject about 4 mg / kg of the composition once every 2 weeks for the first period of time.

25. The method of any one of claims 1-10, wherein the method comprises administering to the subject about 2 mg / kg of the composition once every 4 weeks for the first period of time.

26. The method of any one of claims 1-10, wherein the method comprises administering to the subject about 4 mg / kg of the composition once every 4 weeks for the first period of time.

27. The method of any one of claims 1-26, wherein the anti-TNFo antibody comprises a complementarity determining region (CDR) 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, or 15, or YA.

28. The method of any one of claims 1-26, wherein the anti-TNFo antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16.

29. The method of any one of claims 1-26, wherein the anti-TNFo antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

30. The method of any one of claims 1-26, wherein the anti-TNFo antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16, and wherein the anti-TNFo antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

31. The method of any one of claims 1-30, wherein the anti-TNFo antibody comprises an asparagine-linked glycosylation site within a constant Fc region on at least one of the heavy chains.

32. The method of claim 31, wherein the anti-TNFa antibody comprises an asparagine-linked glycosylation site within the constant Fc region on both of the heavy chains.

33. The method of any one of claims 1 -32, wherein the anti-TNFa antibody is sialylated at Asn 297.

34. The method of any one of claims 1-33, wherein the anti-TNFa antibody comprises no N-Glycolylneuraminic acid (Neu5Gc).

35. The method of any one of claims 1 -34, wherein the anti-TNFa antibody is an immunoglobulin G (IgG) antibody.

36. The method of clam 35, wherein the IgG antibody is an IgG 1 antibody.

37. The method of claim 36, wherein the IgG1 antibody comprises a kappa isotype.

38. The method of any one of claims 1 -37, wherein the anti-TNFa antibody is a chimeric antibody.

39. The method of any one of claims 1-38, wherein the anti-TNFa antibody comprises a C-terminal lysine on at least one of the heavy chains.

40. The method of claim 39, wherein the anti-TNFa antibody comprises a C-terminal lysine on both of the heavy chains.

41. The method of claim 39 or 40, wherein the C-terminal lysine is not clipped.

42. The method of any one of claims 1-41, wherein the composition is administered by an infusion.

43. The method of claim 42, wherein the infusion is an intravenous (IV) infusion.

44. The method of claim 42 or 43, wherein the infusion is administered over a period of at least about 2 hours.

45. The method of any one of claims 1-10, wherein the first period of time is about 6 weeks to about 24 weeks.

46. The method of claim 45, wherein the first period of time is about 8 weeks.

47. The method of claim 45, wherein the first period of time is about 12 weeks.

48. The method of any one of claims 1-47, wherein the subject receives a cumulative dose of about 6 mg / kg to about 30 mg / kg of the composition during the first period of time.

49. The method of claim 48, wherein the subject receives a cumulative dose of about 6 mg / kg of the composition during the first period of time.

50. The method of claim 48, wherein the subject receives a cumulative dose of about 8 mg / kg of the composition during the first period of time.

51. The method of claim 48, wherein the subject receives a cumulative dose of about 12 mg / kg of the composition during the first period of time.

52. The method of claim 48, wherein the subject receives a cumulative dose of about 16 mg / kg of the composition during the first period of time.

53. The method of any one of claims 1 -52, wherein the subject is administered at least 3 doses of the composition.

54. The method of any one of claims 1 -52, wherein the subject is administered at least 4 doses of the composition.

55. The method of any one of claims 1 -52, wherein the subject is administered at least 6 doses of the composition.

56. The method of any one of claims 1 -52, wherein the subject is administered at least 3 doses over a 12-week period of time.

57. The method of any one of claims 1 -52, wherein the subject is administered at least 6 doses over a 12-week period of time.

58. The method of any one of claims 1-57, wherein administration of the composition reduces a level of one or more transcripts selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL6), interleukin 2 receptor (IL2R), tumor necrosis factor alpha (TNFa), C-Reactive Protein (CRP), interleukin 1B (IL1B), interleukin 12 (IL12), interleukin 18 (IL18), interferon gamma (IFNG), interleukin 8 (IL8), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JunB), mitogen-activated protein kinase (MKP1), TNF alpha induced protein 1 (TNFAIP1), TNF alpha induced protein 2 (TNFAIP2), TNF alpha induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL32), intercellular adhesion molecule 1 (ICAM-1), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1A member 1 (SCGB1A1), serum amyloid A1 (SAA1), and vascular adhesion molecule 1 (VCAM-1), relative to a control.

59. The method of claim 58, wherein the level of the one or more transcripts is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

60. The method of any one of claims 1-59, wherein administration of the composition reduces a level of one or more proteins selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL-6), interleukin 2 receptor (IL-2R), tumor necrosis factor alpha (TNF-α), C-Reactive Protein (CRP), interleukin 1B (IL-1B), interferon gamma (IFN-γ), interleukin 8 (IL-8), interleukin 12 (IL-12), interleukin 18 (IL-18), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JUNB), mitogen-activated protein kinase phosphatase 1 (MKP-1), TNF alpha-induced protein 1 (TNFAIP1), TNF alpha-induced protein 2 (TNFAIP2), TNF alpha-induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL-32), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1A member 1 (SCGB1A1), serum amyloid A1 (SAA1), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) relative to a control.

61. The method of claim 60, wherein the level of the one or more proteins is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

62. The method of any one of claims 1-61, wherein administration of the composition improves a Forced Vital Capacity (FVC) measurement in the subject relative to the control or baseline.

63. The method of claim 62, wherein the FVC measurement is improved by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

64. The method of any one of claims 1-63, wherein administration of the composition improves a King’s Sarcoidosis Questionnaire (KSQ) score in the subject relative to the control or baseline.

65. The method of claim 64, wherein the KSQ score is increased by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control.

66. The method of any one of claims 1-65, wherein administration of the composition improves a Leicester Cough Questionnaire (LCQ) score in the subject relative to the control or baseline.

67. The method of claim 66, wherein the LCQ score is increased by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 points relative to the control or baseline.

68. The method of any one of claims 1-67, wherein administration of the composition improves a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

69. The method of claim 68, the STQ score is reduced by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

70. The method of any one of claims 1-69, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP) in the subject relative to the control or baseline.

71. The method of claim 70, wherein the CRP level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

72. The method of any one of claims 1-71, wherein administration of the composition decreases or stabilizes a level of Angiotensin Converting Enzyme (ACE) in the subject relative to the control or baseline.

73. The method of claim 72, wherein the ACE level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

74. The method of any one of claims 1-73, wherein administration of the composition decreases or stabilizes a level of Soluble lnterleukin-2 receptor (slL-2) in the subject relative to the control or baseline.

75. The method of claim 74, wherein the slL-2 level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

76. The method of any one of claims 1-75, wherein administration of the composition decreases or stabilizes a level of Interleukin-6 (IL-6) in the subject relative to the control or baseline.

77. The method of claim 76, wherein the IL-6 level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

78. The method of any one of claims 1-77, wherein administration of the composition decreases or stabilizes a level of Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

79. The method of claim 78, wherein the sTNFa level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

80. The method of any one of claims 1-79, wherein administration of the composition improves a Patient Global Assessment (PGA) score in the subject relative to the control or baseline.

81. The method of claim 80, wherein the PGA score is improved by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

82. The method of any one of claims 1-81, wherein administration of the composition improves a Fatigue Assessment Scale (FAS) score in the subject relative to the control or baseline.

83. The method of claim 82, wherein the FAS score is reduced by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

84. The method of any one of claims 1-83, wherein administration of the composition improves a Modified Medical Research Council (mMRC) Dyspnea Scale score in the subject relative to the control or baseline.

85. The method of claim 84, wherein the mMRC Dyspnea score is improved by at least about 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

86. The method of any one of claims 1-85, wherein administration of the composition improves a 6 Minute Walk Distance (6MWD) in the subject relative to the control or baseline.

87. The method of claim 86, wherein the 6MWD is improved by about 3 min, 5 min, 10 min, 20 min, or 30 min relative to the control or baseline.

88. The method of any one of claims 1-87, wherein administration of the composition improves a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

89. The method of any one of claims 1-88, wherein administration of the composition improves a Short Form Survey (SF-36) score in the subject relative to the control or baseline.

90. The method of claim 89, wherein the SF-36 score is increased by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control or baseline.

91. The method of any one of claims 1-90, wherein administration of the composition reduces corticosteriod use in the subject relative to the control or baseline.

92. The method of claim 91, wherein corticosteriod use in the subject is reduced by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

93. The method of any one of claims 1-92, wherein the subject has one or more of acute sarcoidosis, chronic sarcoidosis, progressive sarcoidosis, pulmonary sarcoidosis, remitting sarcoidosis, refractory sarcoidosis, advanced sarcoidosis, ocular sarcoidosis, cutaneous sarcoidosis, or neurosarcoidosis.

94. The method of any one of claims 1-93, wherein the subject has received an anti-inflammatory medication.

95. The method of any one of claims 1 -93, wherein the subject is receiving an anti-inflammation medication.

96. The method of claim 95, wherein the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline, thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab.

97. The method of claim 96, wherein the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone.

98. The method of any one of claims 1-97, wherein administration of the composition does not result in adverse events (AEs) in the subject relative to control or baseline.

99. The method of any one of claims 1-98, wherein administration of the composition does not result in treatment-emergent adverse events (TEAEs) in the subject relative to the control.

100. The method of any one of claims 1-99, wherein administration of the composition does not result in serious adverse events (SAEs) in the subject relative to the control.

101. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time.

102. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in reducing or tapering concurrentcorticosteriod use in a subject with sarcoidosis relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time.

103. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis a subject with sarcoidosis relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King's Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

104. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

105. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scaleassessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

106. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises199.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;200.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;201.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;202.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;203.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;204.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;205.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;206.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;207.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;208.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

107. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in reducing or tapering concurrent corticosteriod use in a subject with sarcoidosis relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises210.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;211.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;212.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;213.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;214.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;215.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;216.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;217.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;218.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12; (x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;219.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

108. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a quality of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ), a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises221.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;222.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;223.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;224.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;225.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;226.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;227.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10; (viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;228.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;229.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;230.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

109. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in a method of treating or reducing sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises232.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;233.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;234.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;235.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6; (v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;236.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;237.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;238.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;239.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;240.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;241.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

110. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises243.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;244.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;245.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;246.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;247.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;248.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;249.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;250.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;251.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;252.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

111. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks.

112. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in reducing or tapering concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks.

113. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, and wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to a control or baseline.

114. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject once every 4 weeks for a period of 12 weeks, and wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline.

115. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, and wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

116. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises257.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;258.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;259.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;260.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;261.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;262.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;263.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;264.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;265.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;266.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;267.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

15.

117. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in reducing or tapering concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;268.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;269.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;270.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;271.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;272.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;273.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;274.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;275.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;276.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;277.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

15.

118. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises278.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;279.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;280.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;281.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;282.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;283.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;284.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;285.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;286.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;287.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

119. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises289.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;290.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;291.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;292.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;293.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;294.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;295.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;296.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;297.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;298.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

120. A composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for use in treating or reducing sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline and wherein the anti-TNFa antibody comprises300.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;301.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;302.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;303.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;304.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;305.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;306.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;307.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;308.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;309.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15121. The composition of any one of claims 101-110, wherein the dose is about 2 mg / kg of the composition.

122. The composition of any one of claims 101-110, wherein the dose is about 4 mg / kg of the composition.

123. The composition of any one of claims 101-110, wherein about 2 mg / kg of the composition is administered to the subject once every 2 weeks for the first period of time.

124. The composition of any one of claims 101-110, wherein about 4 mg / kg of the composition is administered to the subject once every 2 weeks for the first period of time.

125. The composition of any one of claims 101-110, wherein about 2 mg / kg of the composition is administered to the subject once every 4 weeks for the first period of time.

126. The composition of any one of claims 101-110, wherein about 4 mg / kg of the composition is administered to the subject once every 4 weeks for the first period of time.

127. The composition of any one of claims 101-126, wherein the anti-TNFa antibody comprises a complementarity determining region (CDR) 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, or 15, or YA.

128. The composition of any one of claims 101-126, wherein the anti-TNFa antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16.

129. The composition of any one of claims 101-126, wherein the anti-TNFa antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

130. The composition of any one of claims 101-126, wherein the anti-TNFa antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16, and wherein the anti-TNFa antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

131. The composition of any one of claims 101-130, wherein the anti-TNFa antibody comprises an asparagine-linked glycosylation site within a constant Fc region on at least one of the heavy chains.

132. The composition of claim 131, wherein the anti-TNFa antibody comprises an asparagine-linked glycosylation site within the constant Fc region on both of the heavy chains.

133. The composition of any one of claims 101-132, wherein the anti-TNFa antibody is sialylated at Asn 297.

134. The composition of any one of claims 101-133, wherein the anti-TNFa antibody comprises no N-Glycolylneuraminic acid (Neu5Gc).

135. The composition of any one of claims 101-134, wherein the anti-TNFa antibody is an immunoglobulin G (IgG) antibody.

136. The composition of claim 135, wherein the IgG antibody is an lgG1 antibody.

137. The composition of claim 136, wherein the IgG1 antibody comprises a kappa isotype.

138. The composition of any one of claims 101-137, wherein the anti-TNFa antibody is a chimeric antibody.

139. The composition of any one of claims 101-138, wherein the anti-TNFa antibody comprises a C-terminal lysine on at least one of the heavy chains.

140. The composition of any one of claims 101-138, wherein the anti-TNFa antibody comprises a C-terminal lysine on both of the heavy chains.

141. The composition of claim 139 or 140, wherein the C-terminal lysine is not clipped.

142. The composition of any one of claims 101-141, wherein the composition is administered by an infusion.

143. The composition of claim 142, wherein the infusion is an intravenous (IV) infusion.

144. The composition of claim 142 or 143, wherein the infusion is administered over a period of at least about 2 hours.

145. The composition of any one of claims 101 -110, wherein the first period of time is about 6 weeks to about 24 weeks.

146. The composition of claim 145, wherein the first period of time is about 8 weeks.

147. The composition of claim 145, wherein the first period of time is about 12 weeks.

148. The composition of any one of claims 101-147, wherein the subject receives a cumulative dose of about 6 mg / kg to about 30 mg / kg of the composition during the first period of time.

149. The composition of claim 148, wherein the subject receives a cumulative dose of about 6 mg / kg of the composition during the first period of time.

150. The composition of claim 148, wherein the subject receives a cumulative dose of about 8 mg / kg of the composition during the first period of time.

151. The composition of claim 148, wherein the subject receives a cumulative dose of about 12 mg / kg of the composition during the first period of time.

152. The composition of claim 148, wherein the subject receives a cumulative dose of about 24 mg / kg of the composition during the first period of time.

153. The composition of any one of claims 101-152, wherein the subject is administered at least 3 doses of the composition.

154. The composition of any one of claims 101-152, wherein the subject is administered at least 4 doses of the composition.

155. The composition of any one of claims 101-152, wherein the subject is administered at least 6 doses of the composition.

156. The composition of any one of claims 101-152, wherein the subject is administered at least 3 doses over a 12-week period of time.

157. The composition of any one of claims 101-152, wherein the subject is administered at least 6 doses over a 12-week period of time.

158. The composition of any one of claims 101 -157, wherein administration of the composition reduces a level of one or more transcripts selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL6), interleukin 2 receptor (IL2R), tumor necrosis factor alpha (TNFa), C-Reactive Protein (CRP), interleukin 1B (IL1B), interleukin 12 (IL12), interleukin 18 (IL18), interferon gamma (IFNG), interleukin 8 (IL8), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JunB), mitogen-activated protein kinase (MKP1), TNF alpha induced protein 1 (TNFAIP1), TNF alpha induced protein 2 (TNFAIP2), TNF alpha induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL32), intercellular adhesion molecule 1 (ICAM-1), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1A member 1 (SCGB1A1), serum amyloid A1 (SAA1), and vascular adhesion molecule 1 (VCAM-1), relative to a control.

159. The composition of claim 158, wherein the level of the one or more transcripts is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

160. The composition of any one of claims 101 -159, wherein administration of the composition reduces a level of one or more proteins selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL-6), interleukin 2 receptor (IL-2R), tumor necrosis factor alpha (TNF-a), C-Reactive Protein (CRP), interleukin 1B (IL-1 B), interferon gamma (IFN-y), interleukin 8 (IL-8), interleukin 12 (IL-12), interleukin 18 (IL-18), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JUNB), mitogen-activated protein kinase phosphatase 1 (MKP-1), TNF alpha-induced protein 1 (TNFAIP1), TNF alphainduced protein 2 (TNFAIP2), TNF alpha-induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL-32), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1 A member 1 (SCGB1 A1 ), serum amyloid A1 (SAA1 ), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) relative to a control.

161. The composition of claim 160, wherein the level of the one or more proteins is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

162. The composition of any one of claims 101 -161, wherein administration of the composition improves a Forced Vital Capacity (FVC) measurement in the subject relative to the control or baseline.

163. The composition of claim 162, wherein the FVC measurement is improved by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

164. The composition of any one of claims 101 -163, wherein administration of the composition improves a King’s Sarcoidosis Questionnaire (KSQ) score in the subject relative to the control or baseline.

165. The composition of claim 164, wherein the KSQ score is increased by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control.

166. The composition of any one of claims 101 -165, wherein administration of the composition improves a Leicester Cough Questionnaire (LCQ) score in the subject relative to the control or baseline.

167. The composition of claim 166, wherein the LCQ score is increased by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 points relative to the control or baseline.

168. The composition of any one of claims 101 -167, wherein administration of the composition improves a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

169. The composition of claim 168, the STQ score is reduced by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

170. The composition of any one of claims 101 -169, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP) in the subject relative to the control or baseline.

171. The composition of claim 170, wherein the CRP level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

172. The composition of any one of claims 101-171, wherein administration of the composition decreases or stabilizes a level of Angiotensin Converting Enzyme (ACE) in the subject relative to the control or baseline.

173. The composition of claim 172, wherein the ACE level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

174. The composition of any one of claims 101 -173, wherein administration of the composition decreases or stabilizes a level of Soluble lnterleukin-2 receptor (slL-2) in the subject relative to the control or baseline.

175. The composition of claim 174, wherein the slL-2 level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

176. The composition of any one of claims 101 -175, wherein administration of the composition decreases or stabilizes a level of Interleukin-6 (IL-6) in the subject relative to the control or baseline.

177. The composition of claim 176, wherein the IL-6 level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

178. The composition of any one of claims 101 -177, wherein administration of the composition decreases or stabilizes a level of Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

179. The composition of claim 178, wherein the sTNFa level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

180. The composition of any one of claims 101 -179, wherein administration of the composition improves a Patient Global Assessment (PGA) score in the subject relative to the control or baseline.

181. The composition of claim 180, wherein the PGA score is improved by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

182. The composition of any one of claims 101 -181, wherein administration of the composition improves a Fatigue Assessment Scale (FAS) score in the subject relative to the control or baseline.

183. The composition of any one of claims 182, wherein the FAS score is reduced by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

184. The composition of any one of claims 101 -183, wherein administration of the composition improves a Modified Medical Research Council (mMRC) Dyspnea Scale score in the subject relative to the control or baseline.

185. The composition of claim 184, wherein the mMRC Dyspnea score is improved by at least about 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

186. The composition of any one of claims 101 -185, wherein administration of the composition improves a 6 Minute Walk Distance (6MWD) in the subject relative to the control or baseline.

187. The composition of claim 186, wherein the 6MWD is improved by about 3 min, 5 min, 10 min, 20 min, or 30 min relative to the control or baseline.

188. The composition of any one of claims 101 -187, wherein administration of the composition improves a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

189. The composition of any one of claims 101 -188, wherein administration of the composition improves a Short Form Survey (SF-36) score in the subject relative to the control or baseline.

190. The composition of claim 189, wherein the SF-36 score is increased by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control or baseline.

191. The composition of any one of claims 101 -190, wherein administration of the composition reduces corticosteriod use in the subject relative to the control or baseline.

192. The composition of any one of claims 191, wherein corticosteriod use in the subject is reduced by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

193. The composition of any one of claims 1 -192, wherein the subject has one or more of acute sarcoidosis, chronic sarcoidosis, progressive sarcoidosis, pulmonary sarcoidosis, remitting sarcoidosis, refractory sarcoidosis, advanced sarcoidosis, ocular sarcoidosis, cutaneous sarcoidosis, or neurosarcoidosis.

194. The composition of any one of claims 1-193, wherein the subject has received an anti-inflammatory medication.

195. The composition of any one of claims 1-194, wherein the subject is receiving an anti-inflammation medication.

196. The composition of claim 195, wherein the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline, thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab.

197. The composition of claim 196, wherein the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone.

198. The composition of any one of claims 1 -197, wherein administration of the composition does not results in adverse events (AEs) in the subject relative to control or baseline.

199. The method of any one of claims 1-198, wherein administration of the composition does not result in treatment-emergent adverse events (TEAEs) in the subject relative to the control.

200. The method of any one of claims 1-199, wherein administration of the composition does not result in serious adverse events (SAEs) in the subject relative to the control.

201. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time.

202. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to reduce or taper concurrent corticosteriod use in a subject with sarcoidosis relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time.

203. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King's Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

204. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

205. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

206. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in asubject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises385.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;386.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;387.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;388.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;389.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;390.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;391.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;392.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;393.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;394.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;395.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

15.

207. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to reduce or taper concurrent corticosteriod use in a subject with sarcoidosis relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, and wherein the anti-TNFa antibody comprises396.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;397.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;398.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;399.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;400.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;401.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;402.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;403.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;404.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;405.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;406.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

15.

208. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a quality of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ), a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises407.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;408.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;409.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;410.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;411.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;412.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;413.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;414.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;415.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;416.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

209. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or about 4 mg / kg of the composition is administered to the subject about once every 2 weeks or about once every 4 weeks for a first period of time, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;418.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;419.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;420.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;421.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;422.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;423.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;424.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA; (ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;425.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;426.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

210. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject in need thereof relative to a control, wherein a dose of about 2 mg / kg or 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a first period of time, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline, and wherein the anti-TNFa antibody comprises428.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;429.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;430.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;431.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;432.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7; (vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;433.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;434.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;435.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;436.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;437.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

211. Use of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks.

212. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to reduce or taper concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks.

213. Use of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a periodof 12 weeks, and wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid Toxicity Questionnaire (STQ) score in the subject relative to a control or baseline.

214. Use of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject once every 4 weeks for a period of 12 weeks, and wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline.

215. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules for to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, and wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

216. Use of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises444.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3; (ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;445.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;446.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;447.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;448.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;449.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;450.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;451.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;452.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;453.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

217. Use of a composition comprising an anti-TNFa antibody sialylated with one or more N-acetylneuraminic acid molecules to reduce or taper concurrent corticosteroid use in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, and wherein the anti-TNFa antibody comprises (i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;455.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;456.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;457.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;458.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;459.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;460.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;461.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;462.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;463.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

218. Use of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Forced Vital Capacity (FVC) measurement, a King’s Sarcoidosis Questionnaire (KSQ) score, a Leicester Cough Questionnaire (LCQ) score, and a Steroid ToxicityQuestionnaire (STQ) score in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises465.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;466.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;467.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;468.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;469.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;470.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;471.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;472.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;473.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;474.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;475.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15.

219. Use of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of thecomposition is administered to the subject about once every 4 weeks for a period of 12 weeks, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP), Angiotensin Converting Enzyme (ACE), Soluble Interleukin-2 receptor (sIL-2), Interleukin-6 (IL-6), and Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to a control or baseline, and wherein the anti-TNFa antibody comprises477.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;478.(ii) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;479.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;480.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;481.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;482.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;483.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;484.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;485.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;486.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13;487.(xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

15.

220. Use of a composition comprising an anti-TNFα antibody sialylated with one or more N-acetylneuraminic acid molecules to treat or reduce sarcoidosis in a subject having a diagnosis of pulmonary sarcoidosis, wherein a dose of about 4 mg / kg of the composition is administered to the subject about once every 4 weeks for a period of 12 weeks, wherein administration of the composition improves one or more of a Patient Global Assessment (PGA) score, a Fatigue Assessment Scale (FAS) score, a Modified Medical Research Council (mMRC) Dyspnea Scale score, a 6 Minute Walk Distance (6MWD), and a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline and wherein the anti-TNFa antibody comprises488.(i) a first CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 3;489.(II) a second CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 4;490.(iii) a third CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 5;491.(iv) a fourth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 6;492.(v) a fifth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 7;493.(vi) a sixth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 8;494.(vii) a seventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 10;495.(viii) an eighth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to YA;496.(ix) a ninth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 12;497.(x) a tenth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 13; (xi) an eleventh CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 14; and (xii) a twelfth CDR having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 15221. The use of any one of claims 201 -210, wherein the dose is about 2 mg / kg of the composition.

222. The use of any one of claims 201 -210, wherein the dose is about 4 mg / kg of the composition.

223. The use of any one of claims 201-210, wherein about 2 mg / kg of the composition is administered to the subject once every 2 weeks for the first period of time.

224. The use of any one of claims 201-210, wherein about 4 mg / kg of the composition is administered to the subject once every 2 weeks for the first period of time.

225. The use of any one of claims 201-210, wherein about 2 mg / kg of the composition is administered to the subject once every 4 weeks for the first period of time.

226. The use of any one of claims 201-210, wherein about 4 mg / kg of the composition is administered to the subject once every 4 weeks for the first period of time.

227. The use of any one of claims 201-226, wherein the anti-TNFa antibody comprises a complementarity determining region (CDR) 100% identical to SEQ ID NO: 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, or 15, or YA.

228. The use of any one of claims 201-226, wherein the anti-TNFα antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16.

229. The use of any one of claims 201-226, wherein the anti-TNFα antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

230. The use of any one of claims 201-226, wherein the anti-TNFα antibody comprises a variable heavy (VH) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 16, and wherein the anti-TNFα antibody comprises a variable light (VL) domain having an amino acid sequence at least about 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 9.

231. The use of any one of claims 201-230, wherein the anti-TNFα antibody comprises an asparagine-linked glycosylation site within a constant Fc region on at least one of the heavy chains.

232. The use of claim 231, wherein the anti-TNFα antibody comprises an asparagine-linked glycosylation site within the constant Fc region on both of the heavy chains.

233. The use of any one of claims 201-232, wherein the anti-TNFα antibody is sialylated at Asn 297.

234. The use of any one of claims 201-233, wherein the anti-TNFα antibody comprises no N-Glycolylneuraminic acid (Neu5Gc).

235. The use of any one of claims 201-234, wherein the anti-TNFα antibody is an immunoglobulin G (IgG) antibody.

236. The use of claim 235, wherein the IgG antibody is an IgG 1 antibody.

237. The use of claim 236, wherein the IgG1 antibody comprises a kappa isotype.

238. The use of any one of claims 201-237, wherein the anti-TNFa antibody is a chimeric antibody.

239. The use of any one of claims 201-238, wherein the anti-TNFa antibody comprises a C-terminal lysine on at least one of the heavy chains.

240. The use of any one of claims 201-238, wherein the anti-TNFa antibody comprises a C-terminal lysine on both of the heavy chains.

241. The use of claim 239 or 240, wherein the C-terminal lysine is not clipped.

242. The use of any one of claims 201-241, wherein the composition is administered by an infusion.

243. The use of claim 242, wherein the infusion is an intravenous (IV) infusion.

244. The use of claim 242 or 243, wherein the infusion is administered over a period of at least about 2 hours.

245. The use of any one of claims 201-210, wherein the first period of time is about 6 weeks to about 24 weeks.

246. The use of claim 245, wherein the first period of time is about 8 weeks.

247. The use of claim 245, wherein the first period of time is about 12 weeks.

248. The use of any one of claims 201-247, wherein the subject receives a cumulative dose of about 6 mg / kg to about 30 mg / kg of the composition during the first period of time.

249. The use of claim 248, wherein the subject receives a cumulative dose of about 6 mg / kg of the composition during the first period of time.

250. The use of claim 248, wherein the subject receives a cumulative dose of about 8 mg / kg of the composition during the first period of time.

251. The use of claim 248, wherein the subject receives a cumulative dose of about 12 mg / kg of the composition during the first period of time.

252. The use of claim 248, wherein the subject receives a cumulative dose of about 24 mg / kg of the composition during the first period of time.

253. The use of any one of claims 201 -252, wherein the subject is administered at least 3 doses of the composition.

254. The use of any one of claims 201 -252, wherein the subject is administered at least 4 doses of the composition.

255. The use of any one of claims 201 -252, wherein the subject is administered at least 6 doses of the composition.

256. The use of any one of claims 201 -252, wherein the subject is administered at least 3 doses over a 12-week period of time.

257. The use of any one of claims 201 -252, wherein the subject is administered at least 6 doses over a 12-week period of time.

258. The use of any one of claims 201-257, wherein administration of the composition reduces a level of one or more transcripts selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL6), interleukin 2 receptor (IL2R), tumor necrosis factor alpha (TNFa), C-Reactive Protein (CRP), interleukin 1 B (IL1B), interleukin 12 (IL12), interleukin 18 (IL18), interferon gamma (IFNG), interleukin 8 (IL8), monocyte chemoattractant protein-1 (MCP-1), chemokineligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JunB), mitogen-activated protein kinase (MKP1), TNF alpha induced protein 1 (TNFAIP1), TNF alpha induced protein 2 (TNFAIP2), TNF alpha induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL32), intercellular adhesion molecule 1 (ICAM-1), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1A member 1 (SCGB1A1), serum amyloid A1 (SAA1 ), and vascular adhesion molecule 1 (VCAM-1 ), relative to a control.

259. The use of claim 258, wherein the level of the one or more transcripts is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

260. The use of any one of claims 201-259, wherein administration of the composition reduces a level of one or more proteins selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), interleukin 6 (IL-6), interleukin 2 receptor (IL-2R), tumor necrosis factor alpha (TNF-α), C-Reactive Protein (CRP), interleukin 1B (IL-1B), interferon gamma (IFN-γ), interleukin 8 (IL-8), interleukin 12 (IL-12), interleukin 18 (IL-18), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 1 (CXCL1), chemokine ligand 2 (CXCL2), chemokine ligand 3 (CXCL3), early growth response 1 (EGR1), JunB proto-oncogene (JUNB), mitogen-activated protein kinase phosphatase 1 (MKP-1), TNF alpha-induced protein 1 (TNFAIP1), TNF alpha-induced protein 2 (TNFAIP2), TNF alpha-induced protein 3 (TNFAIP3), syndecan 4 (SDC4), superoxide dismutase 2 (SOD2), cytochrome c oxidase subunit II (COX2), interleukin 32 (IL-32), Krebs von den Lungen-6 (KL-6), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-X-C Motif Chemokine Ligand 9 (CXCL9), Chitotriosidase 1 (CHIT1), secretoglobin family 1A member 1 (SCGB1A1), serum amyloid A1 (SAA1), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) relative to a control.

261. The use of claim 260, wherein the level of the one or more proteins is reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control.

262. The use of any one of claims 201-261, wherein administration of the composition improves a Forced Vital Capacity (FVC) measurement in the subject relative to the control or baseline.

263. The use of claim 262, wherein the FVC measurement is improved by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

264. The use of any one of claims 201-263, wherein administration of the composition improves a King’s Sarcoidosis Questionnaire (KSQ) score in the subject relative to the control or baseline.

265. The use of claim 264, wherein the KSQ score is increased by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control.

266. The use of any one of claims 201-265, wherein administration of the composition improves a Leicester Cough Questionnaire (LCQ) score in the subject relative to the control or baseline.

267. The use of claim 266, wherein the LCQ score is increased by at least about o.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 points relative to the control or baseline.

268. The use of any one of claims 201-267, wherein administration of the composition improves a Steroid Toxicity Questionnaire (STQ) score in the subject relative to the control or baseline.

269. The use of claim 268, the STQ score is reduced by at least about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

270. The use of any one of claims 201-269, wherein administration of the composition decreases or stabilizes a level of one or more of C-Reactive Protein (CRP) in the subject relative to the control or baseline.

271. The use of claim 270, wherein the CRP level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

272. The use of any one of claims 201-271, wherein administration of the composition decreases or stabilizes a level of Angiotensin Converting Enzyme (ACE) in the subject relative to the control or baseline.

273. The use of claim 272, wherein the ACE level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

274. The use of any one of claims 201-273, wherein administration of the composition decreases or stabilizes a level of Soluble lnterleukin-2 receptor (slL-2) in the subject relative to the control or baseline.

275. The use of claim 274, wherein the slL-2 level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

276. The use of any one of claims 201-275, wherein administration of the composition decreases or stabilizes a level of Interleukin-6 (IL-6) in the subject relative to the control or baseline.

277. The use of claim 276, wherein the IL-6 level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

278. The use of any one of claims 201-277, wherein administration of the composition decreases or stabilizes a level of Soluble Tumor Necrosis Factor Alpha (sTNFa) in the subject relative to the control or baseline.

279. The use of claim 278, wherein the sTNFa level is reduced by about 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

280. The use of any one of claims 201-279, wherein administration of the composition improves a Patient Global Assessment (PGA) score in the subject relative to the control or baseline.

281. The use of claim 280, wherein the PGA score is improved by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

282. The use of any one of claims 201-281, wherein administration of the composition improves a Fatigue Assessment Scale (FAS) score in the subject relative to the control or baseline.

283. The use of any one of claims 282, wherein the FAS score is reduced by at least about 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

284. The use of any one of claims 201-283, wherein administration of the composition improves a Modified Medical Research Council (mMRC) Dyspnea Scale score in the subject relative to the control or baseline.

285. The use of claim 284, wherein the mMRC Dyspnea score is improved by at least about 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 20 points relative to the control or baseline.

286. The use of any one of claims 201-285, wherein administration of the composition improves a 6 Minute Walk Distance (6MWD) in the subject relative to the control or baseline.

287. The use of claim 286, wherein the 6MWD is improved by about 3 min, 5 min, 10 min, 20 min, or 30 min relative to the control or baseline.

288. The use of any one of claims 201-287, wherein administration of the composition improves a Likert scale assessment of High-resolution computed tomography (HRCT) in the subject relative to the control or baseline.

289. The use of any one of claims 201-288, wherein administration of the composition improves a Short Form Survey (SF-36) score in the subject relative to the control or baseline.

290. The use of claim 289, wherein the SF-36 score is increased by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 points relative to the control or baseline.

291. The use of any one of claims 201-290, wherein administration of the composition reduces corticosteriod use in the subject relative to the control or baseline.

292. The composition of any one of claims 291, wherein corticosteriod use in the subject is reduced by about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% relative to the control or baseline.

293. The use of any one of claims 201-292, wherein the subject has one or more of acute sarcoidosis, chronic sarcoidosis, progressive sarcoidosis, pulmonary sarcoidosis, remitting sarcoidosis, refractory sarcoidosis, advanced sarcoidosis, ocular sarcoidosis, cutaneous sarcoidosis, or neurosarcoidosis.

294. The use of any one of claims 201-293, wherein the subject has received an anti-inflammatory medication.

295. The use of any one of claims 201 -294, wherein the subject is receiving an anti-inflammation medication.

296. The use of claim 295, wherein the anti-inflammatory medication is selected from the group consisting of a corticosteroid, methotrexate, azathioprine, pentoxifylline, thalidomide, leflunomide, mycophenolate, cyclophosphamide, chloroquine, repository corticotropin (RCI), hydroxychloroquine, efzofitimod, rituximab, adalimumab, golimumab, namilumab, and infliximab.

297. The use of claim 296, wherein the corticosteroid is selected from the group consisting of prednisone, prednisolone, dexamethasone, hydrocortisone, methylprednisolone, betamethasone, cortisone, fludrocortisone, and triamcinolone.

298. The use of any one of claims 201-297, wherein administration of the composition does not results in adverse events (AEs) in the subject relative to control or baseline.

299. The use of any one of claims 201-298, wherein administration of the composition does not result in treatment-emergent adverse events (TEAEs) in the subject relative to the control.

300. The use of any one of claims 201-299, wherein administration of the composition does not result in serious adverse events (SAEs) in the subject relative to the control.

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