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 .
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 (i.e., changing from AIA to pre-AIA ) 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.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-16 in the reply filed on 06/26/2026 is acknowledged.
The traversal is on the ground(s) that the claims of Groups I and II are linked by a single general inventive concept and share the same or corresponding special technical features, namely the production of a solid free- flowing, water-soluble granulated composition of ibuprofen-arginine salt and sucrose by spray-drying an aqueous solution of ibuprofen and L-arginine into a fluidized bed of sucrose carrier particles under defined conditions. Applicant argues that the process of claim 1 and the resulting compositions are interdependent, sharing the same inventive concept.
The Examiner disagrees. The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I-II lack unity of invention because even though the inventions of these groups require the technical features of a solid, water-soluble composition of granules consisting of an ibuprofen-arginine salt and sucrose, these technical features are not special technical features as they do not make a contribution over the prior art over Wang (CN 103304401 A) in view of Mullarney et al. (International Journal of Pharmaceutics 257 (2003) 227–236) (see restriction requirement dated 12/29/2025) (nor in view of Kim and Ou as discussed below).
The requirement is still deemed proper and is therefore made FINAL.
Claims 17-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Title Objection
The title should be brief but technically accurate and descriptive. The term “improved” should not be included in the title. See MPEP 606. The following title is suggested “Manufacturing process for granules of ibuprofen-arginine salt and sucrose”.
Claim Objections
Claim 1 is objected to because of the following informality:
In claim 1, line 2, Ibuprofen should be lowercase. Appropriate correction is required.
Claim Rejections - 35 USC § 112, Second Paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-4 and 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 3 recites the broad recitation “from about 1.5:1 mole to 1.05:1 mole”, and the claim also recites “particularly 1.15:1 mole to 1.05:1 mole” which is the narrower statement of the range/limitation.
Claim 9 recites the broad recitation “within the range 150 µm to 450 µm”, and the claim also recites (#100-40 mesh) and “such as “150 µm to 300 µm or 200 µm to 450 µm” which are the narrower statements of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. To overcome these rejections, “particularly” language, the parenthesis and “such as” language can be removed from the claims.
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 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.
Claim 1 is rejected under 35 U.S.C. 103 as being as being obvious over Kim (KR 100730393 B1) in view of Ou (CN 108057029 A).
Regarding claim 1, Kim discloses a method of producing a combination of ibuprofen, arginine, and water and spraying the solution into a fluidized bed of carrier particles to prepare solid granules (abstract; pg. 2, paragraph 8; pg. 3, middle). Kim discloses the spraying is performed by spray drying (English translation, pg. 2, paragraph 9). The compositions are flowable (pg. 2, bottom). The required components of the method disclosed by Kim are ibuprofen, arginine, a solvent (water preferred – pg. 3, paragraph 6), and a carrier excipient (abstract; pg. 2, bottom – pg. 3, top). Kim discloses the carrier excipient is at least one selected from the group consisting of microcrystalline cellulose, corn starch and colloidal silicon dioxide (pg. 2, bottom – pg. 3, top).
Kim does not disclose sucrose as the carrier excipient.
Ou teaches a pharmaceutical preparation where a zaltoprofen dosage (an NSAID) is produced by a spraying an excipient core (abstract; claim 1; claim 6). Kim teaches that the carrier excipient core is sucrose or microcrystalline cellulose (pg. 2, middle).
Generally, it is prima facie obvious to substitute a known equivalent into a composition, for the same purpose. See MPEP 2144.06. II. In the instant case, since Kim taught microcrystalline cellulose as a carrier excipient, it is prima facie obvious to substitute sucrose for microcrystalline cellulose based on its known equivalency as a carrier core to be used in an NSAID preparation produced by spraying as taught by Ou (pg. 2, middle).
Regarding the claim 1 limitation of the ibuprofen and arginine forming a salt, a chemical composition and its properties are inseparable. MPEP 2112.01 II. Therefore, because the prior art (Kim) discloses a composition with the same components (ibuprofen and arginine in water), the properties the applicant discloses and/or claims (salt formation) are reasonably expected to be necessarily present. Ibuprofen is a weak acid (carboxylic acid group) and arginine is a weak base (guanidino group), in aqueous solution, the carboxylic acid of ibuprofen would be expected to protonate the guanidinium of arginine, forming an ionic salt.
While Kim does not explicitly disclose that the arginine is L-arginine, L-arginine is the naturally occurring stereoisomer and “arginine” is generally known in biological and pharmaceutical contexts to refer to the L-isomer. Nevertheless, there is an obviousness of species when the prior art teaches genus. See MPEP 2144.08.
Claims 2-8 are rejected under 35 U.S.C. 103 as being as being obvious over Kim (KR 100730393 B1) in view of Ou (CN 108057029 A) and further in view of Tu (CN 101810568 A).
The 35 U.S.C. 103 rejection over Kim in view of Ou was previously discussed.
Kim does not disclose that the aqueous solution comprises a molar excess of L-arginine to ibuprofen (instant claim 2), that the ratio of L-arginine to ibuprofen in the aqueous solution is from about 1.5:1 mol to 1.05:1 mol (instant claim 3), that the aqueous solution comprises about 1.1 mol of L-arginine per 1.0 mol of ibuprofen (instant claim 4), that the water has a temperature of from 45-60 degrees C (instant claim 5), that the solution is incubated for a time sufficient for substantially all of the ibuprofen to react with L-arginine to form ibuprofen-arginine salt (instant claim 6), that the aqueous solution is prepared by first dissolving L-arginine in water then adding ibuprofen (instant claim 7), or that the aqueous solution is incubated for up to 60 minutes (instant claim 8).
Tu discloses a method for the preparation of an ibuprofen and arginine solution (abstract). The preparation method includes adding arginine to water and dissolving, then adding ibuprofen at a temperature of 50-60°C and stirring for 20 minutes (pg. 3, bottom – pg. 4). Tu teaches that the molar ratio of arginine to ibuprofen is 1:1 to 1.5:1 (claim 3). Tu teaches that the preparation method leads to an ibuprofen-arginine solution that has good stability, high safety, and good treatment effect (abstract).
Since Kim generally teaches a solution of arginine, ibuprofen and water, it would have been prima facie obvious to one of ordinary skill in the art to use the preparation method of Tu, within the teachings of Kim, because Tu teaches that this preparation method for the production of the ibuprofen-arginine solution leads to a product that has good stability, high safety, and good treatment effect (abstract).
The components in the final solution of Tu are arginine-ibuprofen, and water. While Tu discloses the use of activated carbon in the preparation method, the activated carbon is removed from the solution (pg. 3, bottom – pg. 4), therefore Tu meets the instantly claimed limitation of “preparing an aqueous solution consisting of ibuprofen, arginine, and water”.
Claims 2-4 are rendered prima facie obvious because Tu discloses that the molar ratio of arginine to ibuprofen is 1:1 to 1.5:1 (claim 3). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. See MPEP 2144.05 A.
Claim 5 is rendered prima facie obvious because Tu discloses the water temperature is 50-60°C (pg. 3, bottom – pg. 4). A prima facie case of obviousness exists because of overlap, as previously discussed.
Claims 6 and 8 are rendered prima facie obvious because Tu discloses incubating for 20 minutes (pg. 3, bottom – pg. 4). This would be reasonably expected to be sufficient for substantially all of the ibuprofen to react with the arginine especially as Tu discloses the preparation method allows for salt formation without the need for preparing in advance (pg. 3, first full paragraph from bottom; pg. 2, third full paragraph).
Claim 7 is rendered prima facie obvious because Tu discloses the preparation method includes adding arginine to water and dissolving then adding ibuprofen (pg. 3, bottom – pg. 4).
Claim 9 is rejected under 35 U.S.C. 103 as being as being obvious over Kim (KR 100730393 B1) in view of Ou (CN 108057029 A) and Tu (CN 101810568 A) and further in view of Ziaee et al. (European Journal of Pharmaceutical Sciences, 2019, 127:300-318).
The 35 U.S.C. 103 rejection over Kim in view of Ou and Tu was previously discussed.
Regarding claim 9, the combined teachings of the prior art do not disclose maintaining the claimed spray temperature.
Ziaee teaches that spray drying temperature influences the particle formation process which effects the gradient inside and outside the droplet and the final morphology of the powder such as surface roughness. Ziaee also teaches that the temperature effects the drying time, product stability, and yield (pg. 305, last paragraph – pg. 306).
The spray drying temperature is recognized in the art to have different effects (morphology, surface roughness, product stability, yield) based on the temperature used. Thus, the spray drying temperature is recognized to be result effective. As such, result effective variables can be optimized by routine experimentation, and it would have been prima facie obvious to optimize the spray drying temperature to achieve the desired characteristics (i.e., morphology, surface roughness, product stability, yield) See MPEP 2144.05.
Claims 10-13 is rejected under 35 U.S.C. 103 as being as being obvious over Kim (KR 100730393 B1) in view of Ou (CN 108057029 A) and further in view of Loh et al. (Expert Opin. Drug Deliv. 2011, 8(12):1645-1661).
The 35 U.S.C. 103 rejection over Kim in view of Ou was previously discussed.
Regarding claims 10-12, Kim does not disclose that the spraying occurs from one or more atomization nozzles using a top spray configuration of a bottom spray configuration.
Loh discloses that top-spray and bottom spray configurations are both known orientations of the spray nozzle for spray granulation for drug formation. Loh teaches that top spray is one of the most recognized and well-studied techniques and granules produced from top-spray granulation are characterized by low bulk density and porous surfaces that promote wicking of liquid into the interstitial voids of the granules, thereby promoting their dispersion and disintegration (pg. 1647, right column, top paragraph). Loh teaches that the bottom spray configuration has improved in recent years and is useful as a granulation technique (pg. 1647, right column, third paragraph). Loh teaches that the orientation determines not only the spray pattern of the binding liquid, but also the impingement and subsequent spread of the sprayed droplets on the powder particles. Consequently, this will exert an impact on the characteristics of the granules formed. (pg. 1647, left column, bottom).
Since Kim generally teaches spray granulation for drug formulation, it would have been prima facie obvious to one of ordinary skill in the art to spray from an atomization nozzle using a top or bottom spray configuration, within the teachings of Kim, because Loh teaches that top-spray and bottom spray configurations are both known orientations of the spray nozzle for spray granulation for drug formation. The ordinarily skilled artisan would have been motivated to use top spray because Loh teaches that top spray is one of the most recognized and well-studied techniques and granules produced from top-spray granulation are characterized by low bulk density and porous surfaces that promote wicking of liquid into the interstitial voids of the granules, thereby promoting their dispersion and disintegration (pg. 1647, right column, top paragraph). The ordinarily skilled artisan would have been motivated to use bottom spray because Loh teaches that the bottom spray configuration has improved in recent years and is useful as a granulation technique (pg. 1647, right column, third paragraph). Furthermore, it would not have been inventive for the skilled artisan to have discovered the optimum orientation via routine experimentation, especially as Loh teaches that the orientation determines the impingement and subsequent spread of the sprayed droplets on the powder particles which exerts an impact on the characteristics of the granules formed. (pg. 1647, left column, bottom).
Claim 13 is rendered prima facie obvious because Kim discloses drying the granules on the fluidized bed (pg. 3, middle paragraph).
Claim 14 is rejected under 35 U.S.C. 103 as being as being obvious over Kim (KR 100730393 B1) in view of Ou (CN 108057029 A) and Loh et al. (Expert Opin. Drug Deliv. 2011, 8(12):1645-1661) and further in view of Ziaee et al. (European Journal of Pharmaceutical Sciences, 2019, 127:300-318).
The 35 U.S.C. 103 rejection over Kim in view of Ou and Loh was previously discussed.
Regarding claim 14, Kim does not disclose that the granules are dried at a temperature of 40-60°C until the loss on drying is less than 1.0% w/w.
Ziaee teaches that drying temperature effects the yield of spray dried products and that optimizing the drying conditions improves drying resulting in higher yields (pg. 307, right column, third paragraph).
Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). In this case, the general condition of drying the granules on the fluidized bed has been taught by Kim (pg. 3, middle paragraph); as such, it would not have been inventive for the skilled artisan to have discovered the optimum temperature via routine experimentation, especially as Ziaee teaches that drying temperature effects the yield of spray dried products and optimizing the drying conditions improves drying resulting in higher yields (pg. 307, right column, third paragraph).
Furthermore, Ziaee teaches that residual water in the particles leads to shorter shelf-life and lower yield due to wall stickiness (pg. 310, left column, first paragraph). The ordinarily skilled artisan would be motivated to fully dry the particles in order to reduce the amount of residual water which Ziaee teaches leads to shorter shelf-life and lower yield due to wall stickiness (pg. 310, left column, first paragraph).
Claim 15 is rejected under 35 U.S.C. 103 as being as being obvious over Kim (KR 100730393 B1) in view of Ou (CN 108057029 A) and Loh et al. (Expert Opin. Drug Deliv. 2011, 8(12):1645-1661) and further in view of Kotamarthy (Processes, 2020, 8, 683) and O’Connell (Pharmaceutical Technology Europe, 2005, 17:5).
The 35 U.S.C. 103 rejection over Kim in view of Ou and Loh was previously discussed.
Regarding claim 15, Kim does not disclose that the granules are milled and sifted.
Kotamarthy teaches that milling is used in the pharmaceutical industry to ensure that oversized granules are broken into smaller sized granules that conform to product size specifications (pg. 1, first paragraph).
O’Connell teaches that the use of a sieve (i.e., sifting) in the pharmaceutical industry gets rid of oversized contamination to ensure that ingredients and finished products are quality assured during production and before use (pg. 1).
Since Kim generally teaches a pharmaceutical product, it would have been prima facie obvious to one of ordinary skill in the art to mill and sift the granules, within the teachings of the prior art, because Kotamarthy teaches that milling is used in the pharmaceutical industry to ensure that oversized granules are broken into smaller sized granules that conform to product size specifications (pg. 1, first paragraph) and O’Connell teaches that the use of a sieve (i.e., sifting) in the pharmaceutical industry gets rid of oversized contamination to ensure that ingredients and finished products are quality assured during production and before use (pg. 1).
Claim 16 is rejected under 35 U.S.C. 103 as being as being obvious over Kim (KR 100730393 B1) in view of Ou (CN 108057029 A), Loh et al. (Expert Opin. Drug Deliv. 2011, 8(12):1645-1661), Kotamarthy (Processes, 2020, 8, 683) and O’Connell (Pharmaceutical Technology Europe, 2005, 17:5), and further in view of Yang et al. (US 2014/0134245 A1).
The 35 U.S.C. 103 rejection over Kim in view of Ou, Loh, Kotamarthy, and O’Connell was previously discussed.
Regarding claim 16, Kim discloses that the granules are blended with at least one excipient to form a pharmaceutical composition (pg. 3, paragraph 10).
However, Kim does not disclose that the excipient is selected from the group consisting of sodium bicarbonate, aspartame, sodium saccharine and flavoring.
Yang discloses an ibuprofen tablet with a flavoring [abstract] [0031]. Yang teaches that the flavoring is blended with the other tablet ingredients and adds flavor to the mixture [0031] [0042]-[0044].
Since Kim generally teaches a pharmaceutical composition with ibuprofen, it would have been prima facie obvious to one of ordinary skill in the art to including a flavoring, within the teachings of Kim, because Yang teaches a flavoring agent in a pharmaceutical composition with ibuprofen. The ordinarily skilled artisan would have been motivated to use flavoring because Yang teaches that the flavoring adds flavor to the mixture [0031] [0042]-[0044].
The composition would be reasonably expected to be water soluble as the individual components (i.e., arginine-ibuprofen salt, sucrose) are water soluble.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ashlee E Wertz whose telephone number is (571)270-7663. The examiner can normally be reached Monday - Friday, 8 AM - 5 PM.
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, Sahana Kaup can be reached at 571-272-6897. 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. Unpublished application information in Patent Center is available to registered users. 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.
/ASHLEE E WERTZ/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
Prosecution Insights