Methods for delivering entanercept preparations into a lumen of the intestinal tract using a swallowable drug delivery device

• US 10,300,010 B2
• Filed: 11/16/2017
• Issued: 05/28/2019
• Est. Priority Date: 12/23/2010
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc. (Sanofi )
• Original Assignee: RaNA Therapeutics Inc. (Sanofi )
• Inventors: Imran, Mir
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US15/815,499
• Publication Number:
  US 20180169003A1
• Time in Patent Office: 558 Days
• CPC Class Codes: A61B 17/12099 characterised by the location of the occluder
• CPC Class Codes: A61B 17/12136 Balloons
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 5/00 Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests vaccination appliances for veterinary use A61D1/025 ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug 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 intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Claims

1. A method for delivering Etanercept to a patient, the method comprising:

providing a solid Etanercept dosage shaped as a tissue penetrating member having a pointed tip, the tissue penetrating member configured to be carried by a swallowable capsule and penetrate and be inserted into an intestinal wall, wherein upon ingestion, the capsule advances to the small intestine of the patient; and

delivering the solid Etanercept dosage into the wall of the small intestine by an application of mechanical force upon a surface of the tissue penetrating member from an actuator operably coupled to the tissue penetrating member wherein upon insertion into the intestinal wall, the tissue penetrating member remains to release Etanercept into the blood stream from the intestinal wall by degradation of the of the tissue penetrating member.

2. A method as in claim 1, wherein actuator comprises an expandable member or an expandable balloon.

3. A method as in claim 1, wherein the Etanercept reaches a Cmax in a shorter time period than a time period to achieve a Cmax for an extravascularly injected dose of Etanercept.

4. A method as in claim 3, wherein a tmax for the Etanercept released from the solid dosage is less than about 50% of a tmax for the extravascularly injected dose of Etanercept.

5. A method as in claim 3, wherein a tmax for the Etanercept released from the solid dosage is less than about 30% of a tmax for the extravascularly injected dose of Etanercept.

6. A method as in claim 3, wherein a tmax for the Etanercept released from the solid dosage is less than about 10% of a tmax for the extravascularly injected dose of Etanercept.

7. A method as in claim 1, wherein the solid dosage Etanercept comprises a biodegradable material which degrades within the intestinal wall to release Etanercept into the blood stream.

8. A method as in claim 7, wherein the biodegradable material comprises PGLA, a sugar or maltose.

9. A method as in claim 1, wherein the solid dosage Etanercept comprises at least one pharmaceutical excipient.

10. A method as in claim 9, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

11. A method as in claim 10, wherein the binder comprises PEG.

12. The method of claim 1, wherein a weight percent of Etanercept in the solid dosage comprises between about 8 to 12%.

13. The method of claim 1, wherein a dose of Etanercept in the solid dosage is in a range from about 1 to 5 mg.

14. The method of claim 13, wherein the dose of Etanercept in the solid dosage is in a range from about 2 to about 4 mg.

15. A method as in claim 1, further comprising retaining the solid dosage Etanercept within the intestinal wall after insertion.

16. The method of claim 1, wherein the Etanercept solid dosage produces a long-term release of Etanercept.

17. The method of claim 16, wherein the long term release is over a period of about 6 to 24 hours.

18. The method of claim 1, further comprising:

using the dose of delivered Etanercept to treat an autoimmune disease in the patient.

19. The method of claim 18, where the autoimmune disease is rheumatoid arthritis.

20. The method of claim 18, where the autoimmune disease is psoriatic arthritis.

21. The method of claim 18, where the autoimmune disease is ankylosing spondylitis.

22. The method of claim 18, where the autoimmune disease is juvenile idiopathic arthritis.