Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device

• US 10,307,579 B2
• Filed: 12/05/2017
• Issued: 06/04/2019
• Est. Priority Date: 12/23/2010
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc.
• Original Assignee: RaNA Therapeutics Inc.
• Inventors: Imran, Mir
• Primary Examiner(s): Arnold, Ernst V
• Application Number:
  US15/832,464
• Publication Number:
  US 20180093084A1
• Time in Patent Office: 546 Days
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• 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 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2210/1042 Alimentary tract A61M2210/0618 takes precedence
• 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 29/02 Dilators made of swellable material balloon catheters for angioplasty A61M25/104
• 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 37/0015 by using microneedles
• 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 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2848 against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61

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 a natalizumab preparation into the wall of the small intestine, the method comprising:

swallowing a drug delivery device comprising a capsule, an actuator having a first configuration and a second configuration and the natalizumab preparation operably coupled to the actuator, the natalizumab preparation comprising a therapeutically effective dose of a natalizumab and being shaped as a solid tissue penetrating member, the preparation being contained within the capsule in the first configuration and advanced out of the capsule to penetrate into the intestinal wall in the second configuration; and

actuating the actuator responsive to a condition in the small intestine to penetrate and insert the natalizumab preparation shaped as a solid tissue penetrating member into the wall of the small intestine.

2. The method of claim 1, wherein the condition is a selected pH.

3. The method of claim 2, wherein the pH is above about 7.1.

4. The method of claim 1, wherein a weight percent of natalizumab in the natalizumab preparation is in a range between about 8 to 12%.

5. The method of claim 1, wherein a dose of natalizumab in the natalizumab preparation is in a range from about 1 to 5 mg.

6. The method of claim 5, wherein the dose of natalizumab in the natalizumab preparation is about 2-4 mg.

7. The method of claim 6, wherein the dose of natalizumab in the natalizumab preparation is about 3 mg.

8. The method of claim 1, wherein the natalizumab preparation comprises at least one pharmaceutical excipient.

9. The method of claim 8, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

10. The method of claim 1, further comprising retaining the natalizumab preparation within the intestinal wall after insertion.

11. The method of claim 10, wherein retaining comprises anchoring a portion of the natalizumab preparation in intestinal wall tissue.

12. The method of claim 1, wherein delivering the natalizumab preparation comprises applying a force to the natalizumab preparation.

13. The method of claim 12, wherein the natalizumab preparation is advanced completely into the intestinal wall by such application of force.

14. The method of claim 12, wherein the natalizumab preparation is advanced through the intestinal wall by such application of force.

15. The method of claim 14, wherein the force is a mechanical force applied to a surface of the natalizumab preparation.

16. The method of claim 1, wherein the natalizumab preparation produces a long term release of natalizumab up to about 40 days.

17. The method of claim 1, further comprising:

using the dose of delivered natalizumab to treat an autoimmune disease.

18. The method of claim 17, wherein the autoimmune disease is multiple sclerosis.

19. The method of claim 17, wherein the autoimmune disease is Crohn'"'"'s disease.