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

• US 9,844,655 B2
• Filed: 02/12/2016
• Issued: 12/19/2017
• 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): Arnold, Ernst V
• Application Number:
  US15/043,052
• Publication Number:
  US 20160158516A1
• Time in Patent Office: 676 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 dosage to a patient, the method comprising:

providing a solid natalizumab dosage shaped as a tissue penetrating member; and

penetrating the tissue penetrating member into an intestinal wall after oral ingestion, wherein the natalizumab is released into the blood stream from the solid dosage natalizumab in the intestinal wall.

2. The method of claim 1, wherein the natalizumab released into the blood stream from the solid dosage natalizumab reaches a Cmax in a shorter time period than a time period to achieve a Cmax for an extravascularly injected dose of natalizumab.

3. The method of claim 2, wherein a tmax for the natalizumab released from the solid dosage natalizumab is less than about 80% of a tmax for the extravascularly injected dose of natalizumab.

4. The method of claim 2, wherein a tmax for the natalizumab released from the solid dosage natalizumab is less than about 50% of a tmax for the extravascularly injected dose of natalizumab.

5. The method of claim 2, wherein a tmax for the natalizumab released from the solid dosage natalizumab is less than about 30% of a tmax for the extravascularly injected dose of natalizumab.

6. The method of claim 2, wherein a tmax for the natalizumab released from the solid dosage natalizumab is less than about 10% of a tmax for the extravascularly injected dose of natalizumab.

7. The method of claim 1, wherein the tissue penetrating member is inserted into a wall of the small intestine.

8. The method of claim 1, wherein the solid natalizumab dosage is orally delivered in a swallowable capsule.

9. The method of claim 8, wherein penetrating the tissue penetrating member into the intestinal wall comprises operably coupling the tissue penetrating member to a delivery means having a first configuration wherein the tissue penetrating member is within the capsule, and a second configuration wherein the tissue penetrating member is advanced out of the capsule and into the intestinal wall.

10. The method of claim 9, wherein penetrating the tissue penetrating member into the intestinal wall comprises expanding at least one expandable balloon from the first to the second configuration.

11. The method of claim 1, wherein the solid dosage natalizumab comprises a biodegradable material which degrades within the intestinal wall to release natalizumab into the blood stream.

12. The method of claim 11, wherein the biodegradable material comprises PGLA, a sugar or maltose.

13. The method of claim 11, wherein the solid dosage natalizumab comprises at least one pharmaceutical excipient.

14. The method of claim 13, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

15. The method of claim 14, wherein the binder comprises PEG.

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

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

18. The method of claim 17, wherein the dose of natalizumab in the solid dosage natalizumab is about 3 mg.

19. The method of claim 1, further comprising retaining the solid dosage natalizumab within the intestinal wall after insertion.

20. The method of claim 19, wherein retaining comprises anchoring at least one of a barb or an inverse taper shape of the solid dosage natalizumab in the intestinal tissue.

21. The method of claim 1, wherein penetrating the tissue penetrating member comprises applying a force to the tissue penetrating member, wherein the tissue penetrating member has sufficient stiffness to be advanced completely into the intestinal wall by such application of force.

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

23. The method of claim 22, wherein the long-term release of natalizumab is up to about 40 days.

24. The method of claim 1, wherein the Cmax achieved by delivering the solid dosage natalizumab into the intestinal wall is at least about 10 times greater than the Cmax achieved when the preparation is delivered orally without insertion into the intestinal wall.