• Patients \> 18 years and ≤ 82 years old.

• Patient that meet three (3) or more of the five (5) following criteria.

∙ Dyspnea ≥ 5 on a visual analog scale

‣ Respiratory rate ≥ 24 breaths per minute

‣ Heart rate ≥ 95 beats per minute

‣ Resting SaO2 \< 92% breathing ambient air of the patient's usual oxygen prescription and/or change in saturation \> 3% from baseline

‣ CRP ≥ 10 mg/L

• Established diagnosis of COPD with PFTs showing FEV1/FVC \< 70% or FEV1/VC ratio below the 5th percentile of the predicted value.\[14\]

• Subjects must have adherence with triple therapy \[Inhaled Corticosteroid (ICS), Long-acting beta2-adrenergic agonist (LABA), Long-acting muscarinic antagonist (LAMA)\] for greater than 90 Days prior to consideration of participation in this study.

• With triple therapy onboard, the subject must have ≥ 2 steroid-requiring exacerbations (defined by increased respiratory symptoms of increased cough, dyspnea, sputum, sputum purulence, wheeze, chest tightness) requiring treatment with systemic steroids within the past 12 months OR one exacerbation requiring inpatient hospitalization

• Medically stable with no acute hospitalizations for non-COPD related events within the last 3 months

• Expected life expectancy \> 1 year

• Stable Cardiovascular Disease, with no planned intervention

• No history of pulmonary embolism or embolic event

⁃ Hepatic function \< Class B Child-Pugh criteria

⁃ Renal insufficiency with eGFR \> 60 mL/min/1.73m2

⁃ No history of DVT or thrombotic events

⁃ No history of prior organ transplant

⁃ Female subjects of childbearing potential will need to have a negative pregnancy test performed within 14 days prior to study procedure (if applicable) and be adherent to an accepted method of contraception.

⁃ Male subject will need to adhere to barrier contraception during the course of the trial and for 1 month after completion of the final injection of Cuvitru.

⁃ Ability to sign informed consent