Indian Patents. 264646:METHOD OF PROMOTING BINDING OF ACTIVE AGENTS FOR CRYSTALLINE MICROPARTICLE SURFACES

Title of Invention	METHOD OF PROMOTING BINDING OF ACTIVE AGENTS FOR CRYSTALLINE MICROPARTICLE SURFACES
Abstract	Methods are provided for promoting the adsorption of an active agent to microparticles by modifying the structural properties of the active agent in order to facilitate favorable association to the microparticle.

Full Text	The persent application clais the benefit under 35 U.S.C. 119(e) to united states provisional application serial no. 60/717,524 filed on september 14 2005, and united states provissional................ We Claim: 1. A method of promoting binding of an active agent to a preformed crystalline microparticle in suspension comprising the steps of: i) obtaining a pre-formed microparticle comprised of a diketopiperazine; ii) modifying the chemical potential of the active agent wherein said modifying allows for an energetically favorable interaction between the active agent and microparticle independent of removal of solvent; and ii) adsorbing the active agent onto the surface of the microparticle. 2. The method of claim 1 wherein modifying the chemical potential comprises modifying the structure, flexibility, rigidity, solubility or stability of the active agent. 3. The method of claim 2 wherein modifying the chemical potential of the active agent comprises altering solution conditions. 4. The method of claim 3 wherein altering solution conditions comprises adding an active agent modifier to the solution. 5. The method of claim 4 wherein the active agent modifier is selected from the group consisting of salts, surfactants, ions, osmolytes, alcohols, chaotropes, kosmotropes, acid, base, and organic solvents. 6. The method of claim 5 wherein said salt is sodium chloride. 7. The method of claim 1 further comprising a step of dissolving the active agent in a fluid phase of the suspension of microparticles and changing the pH of the fluid phase. 8. The method of claim 7 wherein the pH is changed prior to the addition of active agent. 9. The method of claim 7 wherein the pH is changed subsequent to the addition of active agent. 10. The method of claim 5 wherein the active agent modifier improves the structural stability or pharmacodynamics of the active agent. 11. The method of claim 1 wherein the active agent is a protein, peptide, polypeptide, small molecule, or nucleic acid molecule. 12. The method of claim 11 wherein the active agent is selected from the group consisting of insulin, ghrelin, growth hormone, and parathyroid hormone (PTH). 13. The method of claim 11 wherein the active agent comprises an antibody or antibody fragment. 14. The method of claim 11 wherein the small molecule is a hydrophobic molecule. 15. The method of claim 14 wherein the small molecule is cyclosporin A. 16. The method of claim 11 wherein the small molecule is an ionizable molecule. 17. The method of claim 2 wherein modifying the chemical potential of the active agent comprises modulating one or more energetically favorable interactions with the microparticle surface. 18. The method of claim 17 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises an electrostatic interaction. 19. The method of claim 17 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises a hydrophobic interaction. 20. The method of claim 17 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises a hydrogen bonding interaction. 21. The method of claim __1 wherein the diketopiperazine is fumaryl diketopiperazine. 22. The method of claim 1 further comprising a step for removing the solvent. 23. A process for preparing a drug delivery composition comprising an active agent and a crystalline microparticle comprising the steps of: providing an active agent solution comprising an active agent molecule; modifying the chemical potential of the active agent; providing a microparticle in a suspension or powder wherein the microparticle comprises a diketopiperazine; and combining said active agent solution with said microparticle suspension or powder. 24. The process of claim 23 wherein modifying the chemical potential of the active agent allows for interaction between the active agent and microparticle. 25. The process of claim 23 wherein modifying the chemical potential of the active agent comprises adding an active agent modifier to the solution. 26. The process of claim 25 wherein the active agent modifier is selected from the group consisting of salts, surfactants, ions, osmolytes, alcohols, chaotropes, kosmotropes, acid, base, and organic solvents. 27. The process of claim 26 wherein the active agent modifier decreases the solubility of the active agent molecule. 28. The process of claim 26 wherein the active agent modifier promotes association between the active agent and a microparticle. 29. The process of claim 26 wherein the active agent modifier improves the structural stability of the active agent molecule. 30. The process of claim 23 wherein the diketopiperazine is fumaryl diketopiperazine.

Full Text

The persent application clais the benefit under 35 U.S.C. 119(e) to united states provisional application serial no. 60/717,524 filed on september 14 2005, and united states provissional................

We Claim:
1. A method of promoting binding of an active agent to a preformed
crystalline microparticle in suspension comprising the steps of:
i) obtaining a pre-formed microparticle comprised of a diketopiperazine;
ii) modifying the chemical potential of the active agent wherein said modifying allows for an energetically favorable interaction between the active agent and microparticle independent of removal of solvent; and
ii) adsorbing the active agent onto the surface of the microparticle.
2. The method of claim 1 wherein modifying the chemical potential comprises modifying the structure, flexibility, rigidity, solubility or stability of the active agent.
3. The method of claim 2 wherein modifying the chemical potential of the active agent comprises altering solution conditions.
4. The method of claim 3 wherein altering solution conditions comprises adding an active agent modifier to the solution.
5. The method of claim 4 wherein the active agent modifier is selected from the group consisting of salts, surfactants, ions, osmolytes, alcohols, chaotropes, kosmotropes, acid, base, and organic solvents.
6. The method of claim 5 wherein said salt is sodium chloride.
7. The method of claim 1 further comprising a step of dissolving the active agent in a fluid phase of the suspension of microparticles and changing the pH of the fluid phase.
8. The method of claim 7 wherein the pH is changed prior to the addition of active agent.
9. The method of claim 7 wherein the pH is changed subsequent to the addition of active agent.
10. The method of claim 5 wherein the active agent modifier improves the structural stability or pharmacodynamics of the active agent.

11. The method of claim 1 wherein the active agent is a protein, peptide, polypeptide, small molecule, or nucleic acid molecule.
12. The method of claim 11 wherein the active agent is selected from the group consisting of insulin, ghrelin, growth hormone, and parathyroid hormone (PTH).
13. The method of claim 11 wherein the active agent comprises an antibody or antibody fragment.
14. The method of claim 11 wherein the small molecule is a hydrophobic molecule.
15. The method of claim 14 wherein the small molecule is cyclosporin A.
16. The method of claim 11 wherein the small molecule is an ionizable molecule.
17. The method of claim 2 wherein modifying the chemical potential of the active agent comprises modulating one or more energetically favorable interactions with the microparticle surface.
18. The method of claim 17 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises an electrostatic interaction.
19. The method of claim 17 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises a hydrophobic interaction.
20. The method of claim 17 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises a hydrogen bonding interaction.
21. The method of claim __1 wherein the diketopiperazine is fumaryl diketopiperazine.
22. The method of claim 1 further comprising a step for removing the solvent.
23. A process for preparing a drug delivery composition comprising an active agent and a crystalline microparticle comprising the steps of:

providing an active agent solution comprising an active agent molecule;
modifying the chemical potential of the active agent;
providing a microparticle in a suspension or powder wherein the microparticle comprises a diketopiperazine; and
combining said active agent solution with said microparticle suspension or powder.
24. The process of claim 23 wherein modifying the chemical potential of the active agent allows for interaction between the active agent and microparticle.
25. The process of claim 23 wherein modifying the chemical potential of the active agent comprises adding an active agent modifier to the solution.
26. The process of claim 25 wherein the active agent modifier is selected from the group consisting of salts, surfactants, ions, osmolytes, alcohols, chaotropes, kosmotropes, acid, base, and organic solvents.
27. The process of claim 26 wherein the active agent modifier decreases the solubility of the active agent molecule.
28. The process of claim 26 wherein the active agent modifier promotes association between the active agent and a microparticle.
29. The process of claim 26 wherein the active agent modifier improves the structural stability of the active agent molecule.
30. The process of claim 23 wherein the diketopiperazine is fumaryl diketopiperazine.

Documents:

1921-delnp-2008-Abstract-(07-01-2015).pdf

1921-delnp-2008-Abstract-(12-09-2014).pdf

1921-delnp-2008-Claims-(07-01-2015).pdf

1921-DELNP-2008-Claims-(11-09-2009).pdf

1921-delnp-2008-Claims-(12-09-2014).pdf

1921-delnp-2008-Correspondence Others-(07-01-2015).pdf

1921-delnp-2008-Correspondence Others-(11-10-2012).pdf

1921-delnp-2008-Correspondence Others-(12-09-2014).pdf

1921-DELNP-2008-Correspondence-251114.pdf

1921-DELNP-2008-Correspondence-Others-(11-09-2009).pdf

1921-delnp-2008-Correspondence-Others-(26-12-2012).pdf

1921-delnp-2008-Description (Complete)-(12-09-2014).pdf

1921-delnp-2008-Form-1-(07-01-2015).pdf

1921-delnp-2008-form-13-(11-09-2009).pdf

1921-DELNP-2008-Form-18-(11-09-2009).pdf

1921-delnp-2008-Form-2-(07-01-2015).pdf

1921-delnp-2008-Form-2-(12-09-2014).pdf

1921-delnp-2008-Form-3-(12-09-2014).pdf

1921-delnp-2008-Form-3-(26-12-2012).pdf

1921-delnp-2008-GPA-(12-09-2014).pdf

1921-delnp-2008-Others-(07-01-2015).pdf

1921-delnp-2008-Petition-137-(12-09-2014).pdf

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Patent Number

264646

Indian Patent Application Number

1921/DELNP/2008

PG Journal Number

03/2015

Publication Date

16-Jan-2015

Grant Date

13-Jan-2015

Date of Filing

05-Mar-2008

Name of Patentee

MANNKIND CORPORATION

Applicant Address

28903 North Avenue Paine Valencia CA 91355 USA

Inventors:

#	Inventor's Name	Inventor's Address
1	HOKENSON, Mark	28337 Mayfair Dr. Valencia CA 91354 USA
2	OBERG, Keith, A.	25850 El Gato Place Valencia CA 91355 USA

PCT International Classification Number

A61K 9/16

PCT International Application Number

PCT/US2006/035822

PCT International Filing date

2006-09-14

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	60/744,882	2006-04-14	U.S.A.
2	60/717,524	2005-09-14	U.S.A.