PROCESS AND APPARATUS FOR THE MANUFACTURE OF SOLID MICROPARTICLES

DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Response to Amendment Claims 1 – 15 are pending. Claims 11 – 15 are withdrawn. Claims 1 - 10 maintained rejected. Claims 1, 3, and 8 are currently amended. In view of the amendment, filed on 07/17/2026, the following rejections are withdrawn from the previous office action, mailed on 04/21/2026. Rejection of claims 1-10 under 35 U.S.C. 112(b) Rejection of claims 1-10 under 35 U.S.C. 103 as being unpatentable over Sievers et al. (US 6,630,121) in view of Chickering, III et al. (US 6,962,006) Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or non-obviousness. Claim(s) 1 - 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sievers et al. (US 6,630,121) in view of Chickering, III et al. (US 6,962,006) and further in view of Reverchon (US 2004/0178529). As to claim 1, Sievers et al. (US ‘121) disclose a process for the manufacture of solid microparticles (see the abstract) comprising: a) providing a fluid mixture comprising one or more molecules of interest (col. 24, claim 12 and col. 25, lines 13-15: a pharmaceutically active substance), one or more compounds selected from the group consisting of lipids, lipid-polymer compounds and polymers (claim 6: excipients which are often of polymeric nature like PEG or starch; col. 5, lines 47-60), and water (col. 4, lines 5-6); b) mixing (col. 4, lines 10-12) the fluid mixture of step a) with supercritical or near supercritical carbon dioxide (CO2) (col. 7, lines 1-4) from a carbon dioxide reservoir 10 (col. 10, line 63) and supercritical nitrogen (col. 7, lines 10-21) from nitrogen reservoir 30 (col. 11, lines 26-27, and Fig. 1) to provide a dispersion of the fluid mixture of step a) and the supercritical nitrogen and the CO2 (according to page 17, line 19, in specification of the instant application, examples of “desiccating gas” is nitrogen, and also according to page 17, line 21, of the specification, the term “plasticizing gas” refers to CO2); [AltContent: textbox (A nozzle (orifice of pressure restrictor 25))][AltContent: arrow][AltContent: arrow][AltContent: textbox (Desiccating gas (N2) source )][AltContent: arrow][AltContent: textbox (Plasticizing gas (CO2) source)] PNG media_image1.png 254 417 media_image1.png Greyscale c) ejecting the dispersion obtained in step b) through a nozzle (orifice of pressure restrictor 25, col. 11, lines 15-18) thereby creating a capillary or pre-atomized flow (col. 7, line 66); and [AltContent: arrow][AltContent: arrow][AltContent: textbox (A gas flow to obtain the solid microparticles)] PNG media_image2.png 417 406 media_image2.png Greyscale d) contacting the capillary or pre-atomized flow obtained (in a drying tube 45, col. 11, lines 24-36, in step c) with a fluid of CO2 (the supercritical fluid is carbon dioxide CO2, col. 7, lines 1-4) to prepare fine dry particles (the gas may be chosen so as to react with the molecule of interest in the course of drying; col. 7, lines 22-29). Also, Sievers et al. (US ‘121) disclose the supercritical fluid is carbon dioxide (CO2) (col. 16, lines 5-10 and lines 13-17) because carbon dioxide is endogenous and relatively non-toxic (col. 7, lines 1-4), however, fail to disclose, as to step d), the supercritical fluid CO2 is swirling or spiraling flow to obtain the solid microparticles, as claimed in claim 1. In the analogous art, Chickering, III et al. (US ‘006) disclose a method for making particles comprising: (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material, through at least one atomizer and into a primary drying chamber having a drying gas inlet, a discharge outlet, and a drying gas flowing therethrough, to form droplets comprising the solvent and the bulk material, wherein the droplets are dispersed in the drying gas; (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form particles dispersed in the drying gas, the particles dispersed in the drying gas being a feed-stream; and (c) flowing the particles of the feed-stream through a jet mill to deagglomerate or grind the particles, wherein the bulk material comprises a pharmaceutical agent. (See col. 25, lines 7-22) [AltContent: textbox (A swirling or spiraling gas flow movement within the drying apparatus (20))] [AltContent: arrow][AltContent: arrow] PNG media_image3.png 420 663 media_image3.png Greyscale Further, Chickering, III et al. (US ‘006) disclose a liquid feed and an atomization gas (e.g., air, nitrogen, etc.) are fed through an atomizer 14. The atomized droplets of solvent and bulk material are formed in the primary drying chamber 12. A drying gas is fed through an optional heater 18 and into a primary drying chamber 12. In the primary drying chamber, the droplets are dispersed in the drying gas, and at least a portion of the solvent is evaporated into the drying gas to solidify the droplets and form a feed a feed-stream of particles dispersed in the drying gas. This feed-stream then exits the primary drying chamber 12 through outlet 16 and enters (optional) secondary drying apparatus (20), which includes a coiled tube through which the feed-stream flows. (col. 6, lines 1-14) Also, Chickering, III et al. (US ‘006) teach the centrifugal force created causes the particles to be thrown toward the wall, and the drying gas falls downward along the wall and then spirals upward through the center when it reaches the bottom, producing a double vortex. (col. 8, lines 33-37) Therefore, as to claim 1, Chickering, III et al. (US ‘006) disclose a swirling or spiraling gas flow movement within the secondary drying apparatus (20) to obtain desired solid fine particles (col. 8, lines 33-37 and Fig. 2). It would have been obvious for one of ordinary skill, prior to the time of applicant’s invention, to modify the operation in step d), as taught by Sievers et al. (US ‘121), through providing a swirling or spiraling movement for the flow in order to improve the efficiency of evaporation of the solvent into the drying gas to solidify the droplets and forming particles dispersed in the drying gas, as suggested by Chickering, III et al. (US ‘006): col. 1, lines 60-64. Sievers et al. (US ‘121) disclose the supercritical fluid is carbon dioxide (CO2) because carbon dioxide is endogenous and relatively non-toxic (col. 7, lines 1-4), Sievers et al. (US ‘121) is silent on explicitly reciting the supercritical carbon dioxide (CO2) is a dense CO2, however, a supercritical CO2 is actually another name for a dense CO2 as evidenced by teaching of Reverchon (US ‘529) where in page 4, lines 1-6 recites “the solubilization in this solution of dense carbon dioxide (compressed, liquid or supercritical)”. Further, Sievers et al. (US ‘121) is silent on reciting that the dense carbon dioxide (CO2) has a pressure in the range of 45 to 65 bar and a temperature of 20 ̊C to 30 ̊C, as claimed in claim 1. In another analogous art, Reverchon (US ‘529) discloses carbon dioxide assisted atomization process at pressures between 60 and 80 bar (preferably between 60 and 70 bar) and at temperatures between 70 ̊C and 100 ̊C. (preferably, between 70 and 80 ̊C). (See ¶ [0052]) Therefore, as to claim 1, Reverchon (US ‘529) discloses CO2 having a pressure in the range of 60 to 65 bar and a temperature of 20 ̊C to 30 ̊C. It would have been obvious for one of ordinary skill in the art, prior to the time of applicant’s invention, to modify the dense CO2, as taught by modified Sievers et al. (US ‘121), through providing a CO2 with a pressure in the range of 20 ̊C to 30 ̊C in order to assure that the maximum quantity of carbon dioxide is dissolved in the liquid, thus, maximizing the process performance, as suggested by Reverchon (US ‘529): ¶ [0015]. As to claim 2, Chickering, III et al. (US ‘006) teach the one or more lipids, lipid-polymer compounds and polymers of the fluid mixture of step a) is selected of poly-oxylglycerides (col. 14, line 48, and col. 16, line 24) As to claim 3, Sievers et al. (US ‘121) disclose the fluid mixture of step a) is in a form of an emulsion (col. 6, line 45), microemulsion (col. 14, lines 21-22), suspension, solution, or concentrated solution (col. 14, lines 19-21) mixture. As to claim 4, Sievers et al. (US ‘121) teach the molecule of interest is hygroscopic. (col. 19, line 27) As to claim 5, Sievers et al. (US ‘121) disclose the desiccating gas (supercritical nitrogen; col. 7, lines 10-21) and/or plasticizing gas (supercritical carbon dioxide CO2) of step b) is selected from the group consisting of nitrogen, CO2 and a mixture thereof. According to page 17, line 19, in specification of the instant application, examples of “desiccating gas” is nitrogen, and also according to page 17, line 21, of the specification, the term “plasticizing gas” refers to CO2. Sievers et al. (US ‘121) does not disclose the desiccating gas and/or plasticizing gas of step b) is provided at a pressure of from 0.2 to 16 bar, as claimed in claim 6, or the expanding liquid or dense CO2 is provided at a pressure before expansion of from 15 to 70 bar However, Chickering, III et al. (US ‘006), as to claim 6, disclose the desiccating gas and/or plasticizing gas is provided at a pressure of from 0.2 to 16 bar (col. 10, lines 6-7: these gas pressures, preferably dry nitrogen, is between 0 and 10 bar, more preferably between 2 and 8 bar), or as to claim 7, Chickering, III et al. (US ‘006) disclose the expanding liquid or dense CO2 is provided at a pressure before expansion of from 15 to 70 bar. (col. 10, lines 6-7) It would have been obvious for one of ordinary skill, prior to the time of applicant’s invention, to modify the pressure of the desiccating gas and/or plasticizing gas in step b), as taught by Sievers et al. (US ‘121), so to be at a pressure of from 0.2 to 16 bar in order to efficiently control the particle production throughput through adjusting the pressure of desiccating gas and/or plasticizing gas, as suggested by Chickering, III et al. (US ‘006): col. 10, lines 7-10. It would have been obvious for one of ordinary skill, prior to the time of applicant’s invention, to modify the expanding liquid or dense CO2 in step d), as taught by Sievers et al. (US ‘121), so to be at a pressure of before expansion of from 15 to 70 bar in order to efficiently control the particle production throughput through adjusting the pressure of desiccating gas and/or plasticizing gas, as suggested by Chickering, III et al. (US ‘006): col. 10, lines 7-10. As to claim 8, Sievers et al. (US ‘121) disclose the capillary or pre-atomized flow obtained in step c) and the expanding liquid or dense CO2 swirling or spiraling flow that are contacted in step d) are ejected at an angle of from 0° to 90° with respect to each other. (col. 13, lines 66-67 and col. 14, lines 1-5: the angle of the conical tip may be varied from very acute to very sharp (from about 5 degrees from the plane of the body of the restrictor to about 89 degrees from the plane of the body of the restrictor) As to claim 9, Sievers et al. (US ‘121) teach the fluid mixture of step a) is provided at a temperature of from 4° C. to 250° C. (col. 17, lines 6-14), step b) is carried out at a temperature of from 20° C. to 250° C. (col. 17, lines 6-14), step c) is carried out at a temperature of from 20° C. to 250° C. (col. 15, lines 31-34), and/or step d) is carried out at a temperature of from −20° C. to +35° C (col. 17, lines 6-14). As to claim 10, Sievers et al. (US ‘121) disclose the process is performed continuous. (col. 15, lines 43-47) Response to Arguments Applicant’s arguments with respect to claim(s) 1 – 10 have been considered but are moot in view of the above new grounds of the rejections. Arguments are mainly directed to the newly added claimed subject matter to amended claim 1 and that neither references of Sievers et al. (US ‘121) and Chickering, III et al. (US ‘006) disclose those newly added limitation to claim 1. However, in the above new grounds of the rejections, a new prior art of Reverchon (US ‘529) is introduced that fully addresses the newly added limitation to claim 1, and therefore, the presented arguments are moot in view of above new grounds of the rejections. Finally, Examiner would like to suggest if Applicant’s Counsel believes that an interview can benefit the prosecution of the instant application, Applicant’s Counsel is kindly invited to contact the undersigned examiner. Conclusion Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Relevant Prior Art The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Shekunov et al. (US 7,208,106) disclose a method of forming particles comprising: providing a solution comprising a solute dispersed or dissolved in a solvent; contacting the solution with a first compressed or liquefied gas at an initial temperature to form a mixture; expanding the mixture at a first temperature to form droplets; contacting the droplets with an extracting fluid at a second temperature at which the solvent is extracted from the droplets to form particles comprising the solute; and separating the particles from the extracting fluid and solvent. (see col. 11, last paragraph, and col. 12, first paragraph) Reverchon et al. (US 7,276,190) disclose a process for producing micro and/or nano particles of solids with a mean diameter ranging between 0.01 and 100 micrometers, the process comprising the steps of: solubilizing a solid in a liquid solvent or a mixture of liquid solvents, the liquid solvent or the mixture of liquid solvents having very low or zero solubility in carbon dioxide under conditions with temperature between 30 and 100.degree. C. and pressure between 50 and 240 bar; solubilizing a dense carbon dioxide in the liquid solvent or the mixture of liquid solvents, the dense carbon dioxide being compressed, liquid or supercritical, wherein solubilization takes place in a saturation chamber loaded with high surface packings at process conditions with temperature between 30 and 100.degree. C. and pressure between 50 and 240 bar; injecting a thus obtained solution through a thin wall injector into a precipitation vessel operated at pressures near atmospheric pressure; and recovering produced powders. (See col. 7, claim 1) Correspondence Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEYED MASOUD MALEKZADEH whose telephone number is (571)272-6215. The examiner can normally be reached M-F 8:30AM-5:00PM. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SUSAN D. LEONG can be reached at (571)270-1487. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /SEYED MASOUD MALEKZADEH/ Primary Examiner Art Unit 1754 09/26/2026