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 .
Detailed Action
This office action is in response to applicant’s communication filed on 7/6/16.
Applicant's election of Group 1, claims 1-8, in the reply filed on 3/23/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.03(a)).
Claims 9-10 are withdrawn from consideration being drawn to the non-elected invention. As a result, claims 1-8 are being examined in this Office Action.
Priority
The applicant claims benefit as follows:
PNG
media_image1.png
166
462
media_image1.png
Greyscale
Claim Rejections – 35 USC 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148
USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 1 03(a) are summarized as follows:
Applicant Claims
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue, and resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-10 are rejected under 35 U.S.C. 103(a) as being unpatentable over Moller et al. (AU 689531, pub date 4/2/1998, text cited herein; which corresponds to US 5869101) in view of Gong et al. (CN 109956860, pub date 7/2/2019, the English translation is used herein), and further in view of Pitt et al. (“Particle design via spherical agglomeration: A critical review of controlling parameters, rate processes and modelling,” Powder Technology, 2018).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Moller et al. teaches a process for producing S(+)-ibuprofen particles having improved flow properties, wherein granular crystalline S(+)-ibuprofen is molten, finely distributed in a medium in which the S(+)-ibuprofen is substantially insoluble, preferably cold water, and rapidly chilled to obtain a fine-grained crystalline primary structure, whereupon the product obtained in agglomerates as a secondary structure is filtered out and dried. (Moller, AU 689531, p. 2, first full paragraph; p. 18, claim 1; p. 20, abstract).
Moller et al. further teaches that the molten active substance solidifies and crystallizes in particle shape, that the particles obtained are substantially spheroid and have good pourability, and that the particles can be directly pressed into tablets or packed into capsules. (Moller, p. 2, first full paragraph).
Moller et al. also teaches that the obtained granules usually do not need to be comminuted, and that it is possible to influence particle size by variation of process parameters. (Moller, p. 2, first full paragraph; p. 3, first full paragraph).
Moller et al. teaches that the amount of shearing action exerted on the medium decisively determines the particle size and dissolution velocity of the S(+)-ibuprofen agglomerate obtained. (Moller, p. 3, second full paragraph).
Moller et al. teaches adding the molten S(+)-ibuprofen to the medium under intensive stirring action, and using high-speed apparatus, such as ultra-turrax or turbo-stirring apparatus. (Moller, p. 4, first full paragraph; p. 15, claims 4-5).
Moller et al. further teaches that the molten S(+)-ibuprofen can be added to the medium in one single pouring step, continuously drop by drop, or injected into the non-solvent medium by means of a heated nozzle. (Moller, p. 6, Example 1; p. 7, Example 5; p. 8, Example 6; p. 15, claims 6-7).
Moller et al. also teaches the use of cold water as the medium in which the S(+)-ibuprofen is substantially insoluble, and teaches that the quantity of cold water should amount to 3 to 7 times, preferably 5 times, the quantity by weight of S(+)-ibuprofen. (Moller, p. 4, second full paragraph; p. 16, claims 11-12).
Moller’s examples use 100 g ibuprofen with 500 g water, 10 kg ibuprofen with 50 kg water, 200 g ibuprofen with 1000 g water, and 300 g ibuprofen with 1.5 kg water, each corresponding to a water:ibuprofen ratio of 5:1, which reads on applicant’s claimed water:ibuprofen range. (Moller, p. 6, Examples 1-2; p. 7, Examples 4-5; p. 8, Example 7).
Moller et al. further teaches that the product has a primary structure of irregularly shaped spheroid crystallites and a secondary structure of agglomerated crystallites having a diameter less than 1 mm and being substantially spheroid. (Moller, p. 12, “Structure characteristics of S(+)-ibuprofen”; p. 17, claim 19).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Moller et al. is deficient in the sense that it does not teach applicant’s particular crystallization conditions and product targets.
Gong et al. teaches a preparation method of ibuprofen spherical crystal, wherein at 75-85 degrees centigrade ibuprofen is used in an ibuprofen-water mixed system, stirring is performed until liquid-liquid phase separation occurs and ibuprofen droplets are dispersed in water, the system is cooled to 1-30 degrees centigrade and continuously stirred until crystallization, and the product is filtered, washed and dried to obtain spherical crystalline ibuprofen. (Gong, p. 1, Abstract; p. 3, Summary; p. 6, claim 1). Gong et al. teaches that ibuprofen has a melting point of 75-77 degrees centigrade and is insoluble in water. (Gong, p. 2, Background). Gong et al. further teaches that different ibuprofen preparations require different crystal habits and particle sizes, and that spherical ibuprofen crystals are desirable because they have high flowability, uniform particles, stability, and good coating and pressing performance. (Gong, p. 2, Background). Gong et al. also teaches that particle size can be adjusted by changing the stirring speed, and that with a 150 mL solution volume, a stirring speed of 250 to 600 rpm provides ibuprofen spherical crystal product having an average particle diameter of about 500-1000 microns. (Gong, p. 3, Summary).
Gong et al.’s examples teach preparing ibuprofen spherical crystals at 75 degrees centigrade, 80 degrees centigrade, and 85 degrees centigrade, cooling to 1 degrees centigrade, 5 degrees centigrade, 20 degrees centigrade, or 30 degrees centigrade, using stirring speeds of 600 rpm, 450 rpm, 300 rpm, and 250 rpm, and filtering, washing, and drying the product. (Gong, pp. 4-6, Examples 1-4).
Gong et al.’s examples further teach spherical particles having average particle sizes of 500 microns, 700 microns, 800 microns, and 1000 microns, angles of repose of 29, 29, 30, and 31 degrees, and tap densities of 0.47, 0.55, 0.50, and 0.51 g/cm3, respectively. (Gong, pp. 4-6, Examples 1-4).
Gong et al. further teaches that the ibuprofen spherical crystal particles have high flowability, an angle of repose between 29 and 31 degrees, and a tap density of 0.47 to 0.55 g/cm3. (Gong, p. 1, Abstract; p. 3, Summary).
Pitt et al. teaches that spherical agglomeration is a particle design technique where crystallization and agglomeration occur simultaneously to yield agglomerated crystals in compacted, spherical form. Pitt et al. teaches that this route improves API handling and tabletability and reduces the need for further downstream processing during pharmaceutical manufacture. (Pitt, p. 2, Abstract; p. 2, Introduction).
Pitt et al. further teaches that crystallization provides an opportunity to tailor micromeritic properties, such as size, size distribution, surface area, morphology, and polymorphic form, as well as functional properties, such as strength, flowability, solubility, and dissolution profile. (Pitt, p. 3, first paragraph).
Pitt et al. teaches that larger, free-flowing particles are required for efficient tableting, and that spherical agglomeration improves micromeritic and functional properties without requiring additional granulation. (Pitt, pp. 3-4).
Pitt et al. also teaches that spherically agglomerated particles have been reported to improve bulk density, flowability, compactibility, and compressibility, and that improved compressibility of ibuprofen agglomerates compared to single crystals is associated with the isotropic texture of the agglomerates. (Pitt, pp. 4-5).
Pitt et al. further teaches that operational parameters affecting precipitation, agglomeration, and resultant particle properties include solvent addition method, bridging liquid amount and addition method, agitation rate, temperature, residence time, particle concentration, initial particle size and morphology, and feed rate. (Pitt, pp. 7 and 10-20).
Pitt et al. teaches that feed rate and injection time affect agglomerate size because faster injection can increase dispersion into smaller droplets, resulting in smaller agglomerates. (Pitt, p. 12, last full paragraph).
Pitt et al. teaches that temperature affects nucleation and crystal growth, and influences agglomerate size, bulk density, and sphericity. (Pitt, pp. 13-14).
Pitt et al. also teaches that the agitation rate influences droplet dispersion and size, agglomerate size, agglomerate growth, porosity, compressive strength, sphericity, flowability, nucleation, and breakage. (Pitt, pp. 18-20).
Pitt et al. further teaches that residence time affects agglomerate size, sphericity, porosity, and strength, and that continued agitation can lead to compaction and an increase in agglomerate density. (Pitt, p. 20).
Since Moller et al. teaches melting ibuprofen, distributing the molten ibuprofen in cold water under stirring, rapidly chilling the molten ibuprofen, and filtering and drying to obtain substantially spheroidal ibuprofen agglomerates having improved pourability and flow properties, it would have been reasonable to expect this to read on applicant’s method of heating ibuprofen to a molten liquid state, dropping the molten ibuprofen into water under stirring conditions, crystallizing the ibuprofen, and post-treating the crystal slurry. Even if Moller et al. does not expressly recite every claimed process parameter, Moller et al. expressly recognizes that particle size is affected by process parameters and that shearing action decisively determines the particle size and dissolution velocity of the obtained ibuprofen agglomerates. (Moller, p. 3, first and second full paragraphs). Thus, the claimed process parameters would have been obvious to optimize because they are known result-effective variables.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Therefore, it would be prima facie obvious to one of ordinary skill in the art at the time of the invention, to modify the process of Moller et al. with the ibuprofen spherical crystallization conditions and product targets taught by Gong et al., and with the process-variable optimization teachings of Pitt et al., because Moller et al. and Gong et al. are both directed to preparing ibuprofen particles or ibuprofen spherical crystals with improved flowability and suitability for direct tableting or capsule filling. Gong et al. confirms that ibuprofen has a melting point in the claimed heating range, is insoluble in water, and forms spherical crystals in water under stirring and cooling conditions. Pitt et al. confirms that spherical agglomeration and spherical crystallization were known particle design techniques used to improve flowability, compressibility, compactibility, and tableability, and that temperature, agitation, feed/addition conditions, residence time, and droplet/particle formation were known variables affecting the final agglomerate size, density, porosity, strength, sphericity, and flowability.
It would have been obvious to pressurize the molten ibuprofen and pass it through a liquid distributor having selected holes because Moller et al. already teaches finely distributing molten ibuprofen, adding the melt drop by drop, and injecting the melt into the non-solvent medium by means of a heated nozzle.
Using pressure and a liquid distributor would merely be a predictable way to feed and finely distribute a molten liquid into water to control droplet size. This is especially true since Pitt et al. teaches that feed rate, injection time, droplet dispersion, and agitation affect the final agglomerate size and properties.
It would also have been obvious to use higher stirring during molten ibuprofen addition and lower stirring during crystal growth because Moller et al. teaches intensive stirring and high-speed stirring tools, Gong et al. teaches stirring speeds of 250-600 rpm for ibuprofen spherical crystal formation, and Pitt et al. teaches that agitation rate controls droplet dispersion, agglomerate size, porosity, compressive strength, sphericity, flowability, nucleation, and breakage.
Also, with regard to applicant's limitations regarding the bulk density, tap density, particle size, and angle of repose, it is the position of the examiner that one of ordinary skill in the art, at the time of the invention, would through routine and normal experimentation determine the optimization of these limitations to provide the best effective variable depending on the result desired. Because Moller et al. teaches diameters of spheroidal ibuprofen agglomerates and improved pourability/flow properties, Gong et al. teaches diameters of ibuprofen spherical crystal particles, angles of repose and tap densities and Pitt et al. teaches that bulk density, flowability, compactibility, compressibility, porosity, sphericity, and agglomerate strength are affected by spherical agglomeration, the examiner asserts that the bulk density, tap density, particle size, and angle of repose are art recognized result-effective variables. Thus it would be obvious in the optimization process to optimize the bulk density, tap density, particle size, and angle of repose. The applicant does not show any unusual and/or unexpected results for the limitations stated. Note that the prior art provides the same effect desired by the applicant, the formation of spherical ibuprofen crystals with high bulk density for the chemical industry.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer Cho Sawyer whose telephone number is (571) 270 1690. The examiner can normally be reached on Monday-Friday 9 AM - 6 PM PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-274-1690.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Jennifer Cho Sawyer
Patent Examiner
Art Unit: 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
Prosecution Insights