Claims for Patent: 9,630,930

Summary for Patent: 9,630,930

Title:	Diketopiperazine microparticles with defined specific surface areas
Abstract:	Disclosed herein are diketopiperazine microparticles having a specific surface area of less than about 67 m.sup.2/g. The diketopiperazine microparticle can be fumaryl diketopiperazine and can comprise a drug such as insulin.
Inventor(s):	Grant; Marshall L. (Newtown, CT), Stowell; Grayson W. (Gaylordsville, CT), Menkin; Paul (Branford, CT)
Assignee:	MannKind Corporation (Valencia, CA)
Application Number:	14/251,513
Patent Claims:	1. A method for forming diketopiperazine microparticles comprising: a) dissolving a diketopiperazine in a water-based solution; b) adding an acid solution to the water-based solution to precipitate the diketopiperazine microparticles out of the solution to form a microparticle suspension; c) adjusting manufacturing conditions to target production microparticles with a specific surface area (SSA) of 52 m.sup.2/g; d) and collecting the precipitate after washing with deionized water; wherein the precipitate comprises diketopiperazine microparticles having a SSA of 35 m.sup.2/g to 67 m.sup.2/g. 2. The method of claim 1 wherein the water-based diketopiperazine solution comprise ammonia. 3. The method of claim 1 wherein the acid solution comprises acetic acid. 4. The method of claim 1, wherein the water-based diketopiperazine solution and the acid solution are at a temperature of 14.degree. C. to 18.degree. C. 5. The method of claim 1, further comprising adding a solution comprising an active agent. 6. The method of claim 5 wherein the active agent comprises at least one of proteins, polypeptides, peptides, nucleic acids, organic macromolecules, synthetic organic compounds, polysaccharides and other sugars, fatty acids, lipids, or antibodies and fragments thereof. 7. The method of claim 5 wherein the active agent comprises at least one of vasoactive agents, neuroactive agents, hormones, anticoagulants, immunomodulating agents, cytotoxic agents, antibiotics, antiviral agents, antigens, infectious agents, inflammatory mediators, hormones, and cell surface antigens. 8. The method of claim 7 wherein the active agent comprises at least one of a cytokine, a lipokine, an enkephalin, an alkyne, a cyclosporin, an anti-IL-8 antibody, an IL-8 antagonist including ABX-IL-8; a prostaglandin including PG-12, an LTB receptor blocker including LY29311, BIIL 284, CP105696; insulin or analogs thereof, growth hormone or analogs thereof, parathyroid hormone (PTH) or analogs thereof, parathyroid hormone related peptide (PTHrP), ghrelin, an obestatin, an enterostatin, a granulocyte macrophage colony stimulating factor (GM-CSF), amylin, an amylin analog, glucagon-like peptide 1 (GLP-1), clopidogrel, PPACK (D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone), oxyntomodulin (OXM), peptide YY(3-36) (PYY), adiponectin, cholecystokinin (CCK), secretin, gastrin, glucagon, motilin, somatostatin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), IGF-1, growth hormone releasing factor (GHRF), integrin beta-4 precursor (ITB4) receptor antagonist, nociceptin, nocistatin, orphanin FQ2, calcitonin, CGRP, angiotensin, substance P, neurokinin A, pancreatic polypeptide, neuropeptide Y, delta-sleep-inducing peptide and vasoactive intestinal peptide. 9. The method of claim 5 wherein the active agent comprises a peptide. 10. The method of claim 9 wherein the active agent comprises insulin or an analog thereof. 11. The method of claim 9 wherein the active agent comprises GLP-1 or an analog thereof. 12. The method of claim 5 wherein the active agent is adsorbed to the microparticle. 13. The method of claim 12 wherein the SSA of the microparticle is reduced following adsorption of the active agent. 14. The method of claim 1 wherein the diketopiperazine is fumaryl diketopiperazine. 15. The method of claim 8 wherein the insulin is human insulin. 16. The method of claim 1 wherein collecting the precipitate comprises tangential flow filtration. 17. A method of forming diketopiperazine microparticles with an SSA of 35 m.sup.2/g to 67 m.sup.2/g within a 95% confidence limit comprising, feeding equal masses of 10.5 wt % acetic acid and 2.5 wt % diketopiperazine solutions at 14.degree. C. to 18.degree. C. through a high shear mixer. 18. The method of claim 17 further comprising adding a solution comprising an active agent to a suspension of the microparticles. 19. The method of claim 18, further comprising increasing the pH of the suspension of diketopiperazine microparticles to pH 4.5 with an aqueous ammonia solution. 20. The method of claim 18, further comprising increasing the concentration of ammonia in the suspension of diketopiperazine microparticles to yield a pH of from pH 3.5 to pH 4.5. 21. The method of claim 18 wherein the active agent comprises at least one of proteins, polypeptides, peptides, nucleic acids, organic macromolecules, synthetic organic compounds, polysaccharides and other sugars, fatty acids, lipids, or antibodies and fragments thereof.

Details for Patent 9,630,930

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	10/28/1982		2029-06-12
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	12/29/2015		2029-06-12
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	08/06/1998		2029-06-12
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	03/31/1994		2029-06-12
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	05/25/2018		2029-06-12
Novo Nordisk Inc.	NOVOLIN R	insulin human	Injection	019938	06/25/1991		2029-06-12