Methods and devices for treating a disease with biotherapeutics

Abstract

This disclosure features methods and devices for treating diseases with orally-delivered biotherapeutics.

1 .- 935 . (canceled) 
     
     
         936 . A method of treating a disease or condition in a subject in need thereof, the method comprising:
 trans-epithelially administering a dispensable substance to the gastrointestinal (GI) tract of the subject, wherein the trans-epithelial administration comprises:
 orally administering an ingestible device comprising the dispensable substance to the subject, wherein the ingestible device is configured for trans-epithelial delivery of the dispensable substance to the GI tract of the subject, and the dispensable substance comprises a pharmaceutical formulation comprising a therapeutically effective amount of a tumor necrosis factor alpha (TNF-alpha) inhibitor; and 
 releasing the dispensable substance from the ingestible device as at least one jet to a desired location of the GI tract of the subject; 
   wherein the disease is responsive to treatment with the TNF-alpha inhibitor.   
     
     
         937 . The method of  claim 936 , wherein the trans-epithelial administration directly delivers the dispensable substance to the submucosa of the GI tract of the subject. 
     
     
         938 . The method of  claim 936 , wherein the desired location of the GI tract is the small intestine. 
     
     
         939 . The method of  claim 936 , wherein the desired location of the GI tract is the jejunum. 
     
     
         940 . The method of  claim 936 , wherein the trans-epithelial administration provides systemic uptake of the TNF-alpha inhibitor that is at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 30% relative to intravenous or subcutaneous administration of the same amount of the TNF-alpha inhibitor. 
     
     
         941 . The method of  claim 936 , wherein the trans-epithelial administration provides an area under the curve (AUC) of the TNF-alpha inhibitor in systemic circulation over time (AUCTE) that is at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 30% of the AUC in systemic circulation over time provided by intravenous administration of the same amount of the TNF-alpha inhibitor (AUCIV) or by subcutaneous administration of the same amount of the TNF-alpha inhibitor (AUCSC). 
     
     
         942 . The method of  claim 936 , wherein the trans-epithelial administration provides a maximum plasma concentration (Cmax) of the TNF-alpha inhibitor in systemic circulation ((Cmax)TE) that is at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 30% of the Cmax in systemic circulation provided by intravenous administration of the same amount of the TNF-alpha inhibitor ((Cmax)IV) or by subcutaneous administration of the same amount of the TNF-alpha inhibitor ((Cmax)SC). 
     
     
         943 . The method of  claim 936 , wherein the pharmaceutical formulation is a liquid solution or suspension. 
     
     
         944 . The method of  claim 936 , wherein the dispensable substance has a peak fluid pressure of from about 200 psig to about 400 psig, about 275 psig to about 375 psig, about 275 psig to about 350 psig, or about 275 psig to about 325 psig 
     
     
         945 . The method of  claim 936 , wherein the at least one jet has a mean jet velocity of from about 20 m/s to about 30 m/s, or about 20 m/s, about 21 m/s, about 22 m/s, about 23 m/s, about 24 m/s, about 25 m/s, about 26 m/s, about 27 m/s, about 28 m/s, about 29 m/s or about 30 m/s. 
     
     
         946 . The method of  claim 936 , wherein the volume of the dispensable substance released from the ingestible device is from about 50 microliters to about 800 microliters, about 50 microliters to about 500 microliters, from about 100 microliters to about 450 microliters, from about 200 microliters to about 400 microliters, from 250 microliters to about 400 microliters, or from about 300 microliters to about 400 microliters. 
     
     
         947 . The method of  claim 946 , wherein the volume of the dispensable substance released from the ingestible device is from about 200 microliters to about 400 microliters. 
     
     
         948 . The method of  claim 936 , wherein releasing the dispensable substance from the ingestible device as at least one jet to a desired location of the GI tract of the subject is at a peak jet power of about 1 Watt to about 3 Watts, about 1.3 Watts to about 2.8 Watts, or about 1.5 Watts to about 2.5 Watts. 
     
     
         949 . The method of  claim 936 , wherein the disease or condition is selected from the group consisting of gastrointestinal, respiratory, musculoskeletal, inflammatory, dermatologic, ocular, neurologic, psychiatric, cardiovascular, immune, autoimmune, infection, hematologic, genitourinary/sexual function, cancer, endocrine, metabolic, and combinations thereof. 
     
     
         950 . The method of  claim 949 , wherein the disease or condition is inflammatory bowel disease. 
     
     
         951 . The method of  claim 950 , wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. 
     
     
         952 . The method of  claim 949 , wherein the disease or condition is an inflammatory, immune, or autoimmune disease or condition selected from allergy, asthma, coeliac disease, glomerulonephritis, chronic peptic ulcer, tuberculosis, rheumatoid arthritis, juvenile rheumatoid arthritis, spondylarthritis, psoriasis, psoriatic arthritis, hidradenitis suppurativa, pyoderma gangrenosum, ankylosing spondylitis, Uveitis (UV), periodontitis, ulcerative colitis and Crohn's disease, sinusitis, active hepatitis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver fibrosis, liver cirrhosis, alcoholic fatty liver disease, alcoholic hepatitis, alcoholic liver disease, systemic lupus erythematosus (SLE, Lupus), preperfusion injury, multiple sclerosis (MS), transplant rejection, graft versus host disease, dermatomyositis, interstitial lung disease, lupus nephritis, motor neurone disease, osteoarthritis, myasthenia gravis, polymyositis, cholecystitis, scleroderma, Sjoegrens syndrome, Wegener granulomatosis, and combinations thereof. 
     
     
         953 . The method of  claim 936 , wherein the TNF-alpha inhibitor is selected from the group consisting of certolizumab pegol, etanercept, golimumab, infliximab, opinercept, ozoralizumab and tulinercept; and biosimilars thereof. 
     
     
         954 . The method of  claim 936 , wherein the TNF-alpha inhibitor is adalimumab or a biosimilar thereof. 
     
     
         955 . The method of  claim 936 , wherein the TNF-alpha inhibitor has a molecular weight of at least about 20 kDa, at least about 30 kDa, at least about 40 kDa, at least about 50 kDa or at least about 60 kDa.