Anti-interleukin antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device

Abstract

Described are swallowable devices, preparations and methods for delivering therapeutic agents within the GI tract such as neutralizing proteins (NP), particularly antibodies which neutralize interleukins. Many embodiments provide a swallowable device e.g., a capsule for delivering various agents into the intestinal wall (IW). Embodiments also provide agent preparations that are configured to be contained within the capsule, advanced from the capsule into the 1W and degrade to release the agent into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW. Embodiments of the invention are particularly useful for the delivery of interleukin NP’ s (INP) for treatment of inflammatory conditions where such INP’s are poorly absorbed, tolerated and/or degraded within the GI tract.

What is claimed is: 
     
         1 . A therapeutic preparation comprising an anti-interleukin antibody (AI-antibody) in solid form, the preparation shaped as a solid tissue penetrating member configured to penetrate and be inserted into an intestinal wall after oral ingestion by an application of mechanical force on the tissue penetrating member at a location in the upper or mid portion of the small intestine prior to the peyer’s patches to avoid an immune response to the tissue penetrating member by the peyer’s patches, wherein after insertion, the tissue penetrating member is retained within the intestinal wall and releases the AI-antibody into the blood stream to attenuate a biological effect of an interleukin in the body; and wherein any adverse reaction from said release of the AI antibody is less than that associated with parenteral injected delivery of the AI-antibody. 
     
     
         2 . The preparation of  claim 1 , wherein the attenuated biological effect of the interleukin is a pro-inflammatory response. 
     
     
         3 . The preparation of  claim 1 , wherein the adverse reaction is one or more of of an injection site reaction, anaphylactic reaction, anaphylactic shock, edema, headache, immunogenic reaction, production of antibodies against the AI-antibody or reduced efficacy of the AI antibody. 
     
     
         4 . The preparation of  claim 1 , wherein the AI-antibody comprises an antibody to a member of the interleukin-17 family of cytokines. 
     
     
         5 . The preparation of  claim 4 , wherein the AI-antibody is one of secukinumab, Ixekizumab, or brodalumab. 
     
     
         6 . The preparation of  claim 1 , wherein the AI-antibody is released into the blood stream from the intestinal wall to achieve a C max  in a shorter time period than a time period to achieve a C max  for an extravascularly injected dose of the AI-antibody. 
     
     
         7 . The preparation of  claim 6 , wherein a t max  for the AI-antibody released from the tissue penetrating member is about 50% of a t max  for the extravascularly injected dose of AI-antibody. 
     
     
         8 . The preparation of  claim 6 , wherein a t max  for the AI-antibody released from the tissue penetrating member is about 10% of a t max  for the extravascularly injected dose of AI-antibody. 
     
     
         9 . The preparation of  claim 1 , wherein the extravascular injection is a subcutaneous injection or an intramuscular injection. 
     
     
         10 . The preparation of  claim 1 , wherein the preparation is adapted to be orally delivered in a swallowable capsule. 
     
     
         11 . The preparation of  claim 10 , wherein the preparation is adapted to be operably coupled to a delivery means having a first configuration and a second configuration, the preparation being contained within the capsule in the first configuration and advanced out of the capsule and into the intestinal wall in the second configuration. 
     
     
         12 . The preparation of  claim 11 , wherein the delivery means comprises at least one expandable balloon having an expanded and a non-expanded state and the first configuration is the non-expanded state and the second configuration is the expanded state. 
     
     
         13 . The preparation of  claim 1 , wherein the preparation comprises a biodegradable material which degrades within the intestinal wall to release the AI-antibody into the blood stream. 
     
     
         14 . The preparation of  claim 13 , wherein the biodegradable material comprises PGLA, polyethylene oxide, a sugar, or maltose. 
     
     
         15 . The preparation of  claim 1 , wherein the preparation comprises at least one of a binder, a preservative, or a disintegrant. 
     
     
         16 . The preparation of  claim 1 , wherein a weight percent of AI-antibody in the tissue penetrating member comprises between about 8 to 12%. 
     
     
         17 . The preparation of  claim 1 , wherein the AI-antibody is contained in the tissue penetrating member in a shaped section. 
     
     
         18 . The preparation of  claim 17 , wherein the shaped section has a cylinder or pellet shape. 
     
     
         19 . The preparation of  claim 6 , wherein the C max  achieved by delivering the preparation by insertion into the intestinal wall is substantially greater than a Cmax achieved when the preparation is delivered orally without insertion into the intestinal wall. 
     
     
         20 . The preparation of  claim 1 , wherein the preparation is configured to produce a long-term release of AI-antibody to produce a selectable t ½ . 
     
     
         21 . The preparation of  claim 20 , wherein the t ½  is about 40 days. 
     
     
         22 . The preparation of  claim 1 , wherein a dose of AI-antibody in the preparation is in a range from about 1 to 5 mg. 
     
     
         23 . The preparation of  claim 22 , wherein a dose of AI-antibody in the preparation is in a range from about 2 to 4 mg. 
     
     
         24 . A therapeutic preparation comprising an anti-interleukin antibody (AI-antibody), the preparation adapted for insertion and retention in an intestinal wall after oral ingestion by an application of mechanical force on the preparation at a location in the upper or mid portion of the small intestine prior to the peyer’s patches to avoid an immune response to the preparation by the peyer’s patches, wherein upon insertion, the preparation is degraded by fluids within the intestinal wall to release the AI-antibody into the bloodstream from the intestinal wall to achieve a t ½  that is greater than a t ½  for orally ingested AI-antibody that is not inserted into the intestinal wall and wherein any adverse reaction from said release of AI-antibody is less than that associated with parenteral injected delivery of AI-antibody. 
     
     
         25 . The preparation of  claim 24 , wherein the t ½  of the AI-antibody inserted into the intestinal wall is at least about 10 times greater than the t ½  for the orally ingested AI-antibody that is not inserted into the intestinal wall.