Office Action Predictor
Last updated: April 15, 2026
Application No. 18/527,530

FERMENTATIVELY-PRODUCED RETINOID CONTAINING COMPOSITIONS, AND THE METHDOS OF MAKING AND USING THE SAME

Final Rejection §103§112
Filed
Dec 04, 2023
Examiner
WELLS, LAUREN QUINLAN
Art Unit
1622
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Dsm Ip Assets B.V.
OA Round
4 (Final)
43%
Grant Probability
Moderate
5-6
OA Rounds
2y 11m
To Grant
99%
With Interview

Examiner Intelligence

Grants 43% of resolved cases
43%
Career Allow Rate
92 granted / 213 resolved
-16.8% vs TC avg
Strong +58% interview lift
Without
With
+57.8%
Interview Lift
resolved cases with interview
Typical timeline
2y 11m
Avg Prosecution
79 currently pending
Career history
292
Total Applications
across all art units

Statute-Specific Performance

§101
1.0%
-39.0% vs TC avg
§103
34.3%
-5.7% vs TC avg
§102
14.6%
-25.4% vs TC avg
§112
27.4%
-12.6% vs TC avg
Black line = Tech Center average estimate • Based on career data from 213 resolved cases

Office Action

§103 §112
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 responsive to Applicant’s Arguments/Remarks and Amendment, filed 12/16/2025, which amended claims 1, 4, 12, 34, and 44, and cancelled claims 7, 43, and 47. Claims 1-5, 10, 12, 14, 17, 19, 21-24, 26, 28-30, 32-34, 36-37, 40, 42 and 44 are pending. Priority The instant application claims priority to the following: PNG media_image1.png 73 649 media_image1.png Greyscale Election/Restrictions Applicant elected without traverse, retinyl acetate as the retinoid component, retinyl palmitate as the fermentative residue, and crystalline as the structure, in the reply filed on 07/01/2024 and the phone call on 07/10/2024 (see Interview Summary dated 07/10/2024). In the course of the search, the election of species requirement was broadened to include retinyl palmitate as the retinoid component, and retinyl acetate, and ethanol as fermentative residues. Claims 10, 17, 19, 22, 26, 28-30, and 32-33, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Claims 1-5, 12, 14, 21, 23-24, 34, 36-37, 40, 42, and 44 have been examined on the merits herein. REJECTIONS WITHDRAWN The status for each rejection and/or objection in the previous Office Action is set out below. 35 U.S.C. § 112(b) Applicant’s amendment to claim 4 is sufficient to overcome this rejection. 35 U.S.C. § 112(d) The deletion of claims 7 is sufficient to overcome the rejection over this claim. Applicant’s amendment to claim 34 is sufficient to overcome the rejection over this claim. 35 U.S.C. § 103 over US PG-PUB 2020/0231993 to Balch; over US PG-PUB 2020/0231993 to Balch in view of KR0146221; and over US 2020/0231993 to Balch in view of KR0146221 and further in view of JP2001213970. Applicant’s amendment to independent claim 1 that deletes optionally in line 1 of the claim, is sufficient to overcome this rejection, since Balch does not teach dry crystalline forms, and there is no motivation to modify the form of the fermentation product of Balch to a dry crystalline form. Regarding the rejection of Balch in view of KR0146221, while KR ‘221 teaches liquid crystal cosmetic compositions comprising forms containing vitamin A palmitate, there is no motivation to select the liquid crystals of KR ‘221 as the composition form of Balch. Balch is directed toward methods of producing vitamin A. However, Balch does not teach the vitamin A as components of products, such as cosmetic or pharmaceutical compositions. KR ‘221 is specifically directed toward cosmetic compositions. An ordinary skilled artisan would not have been motivated to select a cosmetic composition form comprising vitamin A, as taught by KR ‘221, as the form of a composition in a process of making vitamin A, as taught by Balch. Moreover, the crystal vitamin A composition of KR ‘221 are liquid crystal cosmetic compositions and instant claim 1 recites a dry crystalline form. 35 U.S.C. § 103 over US 4,022,913 to Newmark in view of US 3,384,633 to Kardys Applicant’s amendment to independent claim 1 that deletes optionally in line 1 of the claim, is sufficient to overcome this rejection, since Newmark does not teach dry crystalline forms. Newmark specifically teaches its composition as stabilized against the formation of crystals by vitamin A palmitate (abstract; Col. 10, claim 1). Newmark teaches “These preparations contain a high potency of vitamin A activity, yet remain fluid and non-crystalline in the lipophilic solvent systems used to prepare such preparations” (Col. 1, lines 1-14). Thus, Newmark teaches away from a dry crystalline form. Moreover, the compositions of Newmark are liquid (Col. 10, claim 1; Col. 2, lines 56-63). REJECTIONS-NEW & MODIFIED In view of Applicant’s amendments to the claims that limit the composition to a “dry crystalline form,” the prior art rejections are new. In view of an amendment to claim 12, the 112(d) rejection is modified. Claim Interpretation -In claim 1, the phrase “dry crystalline form” is interpreted as a composition lacking any liquid component and behaving and appearing as a granular or powder composition. See [075] of the instant Specification. Claim Objections (New) Claim 1 is objected to because of the following informalities: -In claim 1, (2), the term “thereof” should be deleted. This term is a typo. The instant specification teaches fermentative residues as FAREs or fermentation carbon sources, or as “fermentative residues thereof” in reference to “a retinoid component comprising a mixture of cis-isomers and trans-isomers.” See [013], [014], [015], [023], [024], [029], [053], [054], [055], [059], [061], and [070], of the instant specification. Appropriate correction is required. Claim Rejections - 35 USC § 112(d) The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. (Maintained and Modified) Claims 12, 14 and 21 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. -While the amendment to claim 12, deletes the percent weights, it does not amended the “one or more FAREs” recitation. Claim 12 depends from 1, wherein claim 1 recites, “FARE” and “the FARE” (lines 5 and 12). Claim 12 recites, “wherein the fermentative residue comprises one or more FAREs.” Since claim 1 only recites a single FARE, claim 12 broadens the scope of instant claim 1 by reciting more than one FARE; claim 12 fails to further limit the subject matter of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. All other claims not specifically recited are rejected for depending from an indefinite claim and failing to cure the deficiency. 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 (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. 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. (New) Claims 1-5, 12, 21, 23-24, 34, 36, 40, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (Efficient two-step chemo-enzymatic synthesis of all-trans-retinyl palmitate with high substrate concentration and product yield, App Microbio and Biotech, published 2015, IDS of 07/24/2024) in view of Urwin (A structured Approach to Cope with Impurities during Industrial Crystallization Development, OPR&D, published 202, PTO-892) and Moynihan (Impurity Occurrence and Removal in Crystalline Products from Process Reactions, OPR&D, published 2017, PTO-892). Liu teaches an efficient two-step chemo-enzymatic synthesis of all-trans-retinyl palmitate with high substrate concentration and product yield. Lu teaches that after purification, all-trans retinyl palmitate was obtained with above 99% of purity (title, abstract; pg. 8892, Scheme 1). Lu teaches the all-trans-retinyl palmitate as a crystal (pg. 8893, Col. 2, 1st full paragraph). Lu teaches that after washing four times by distilled water, ethanol was almost completely removed and the yield of retinyl palmitate reached 97.3% (paragraph spanning pgs. 8896-8897). Lu teaches the following reaction scheme: PNG media_image2.png 164 1085 media_image2.png Greyscale (pg. 8892). Lu teaches 9-cis-retinyl palmitate and 13-cis-retinyl palmitate as determined in the all-trans-retinyl palmitate product (pg. 8894, Col. 1, 1st full paragraph). Thus, Lu teaches a crystal comprising about 97.3% retinyl palmitate, with approximately 99% all-trans-retinyl palmitate. Lu differs from that of instant claim 1 in that it does not explicitly teach a FARE or fermentation carbon source, and thus a ratio of the retinoid component to the FARE/fermentation carbon source of greater than 4:1. Urwin teaches a structured approach to cope with impurities during industrial crystallization development (title, abstract). Urwin teaches that the perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization, unwanted impurities routinely contaminate a crystallization product (abstract). Ideally, after crystallization, the resulting solid particulate product is composed of one single target compound with all other chemical entities remaining in the liquid phase for disposal. In reality, the majority of the impurity is rejected by the growing crystals, but some impurity compromises the final product purity. It is essential to remove residual impurity compounds to below a threshold concentration value (pg. 1443, “Introduction”). An array of mechanisms of impurity incorporation into a solid particular product exist—agglomeration, surface deposition, inclusions, cocrystal formation, and solid solution formation (pg. 1443, Col. 2, 1st full paragraph). Agglomerates occur when particles aggregate during a crystallization to form larger agglomerates, and pockets of impurity rich mother liquor become trapped between the intergrown particles (pg. 1443, Col. 2). Surface Deposition occurs when residual mother liquor that has not been adequately washed away is present on the crystal surface of the final product particles (pg. 1444, Col. 1). Inclusions occur through the inclusion of impurity rich mother liquor within the growth crystal (pg. 1444, Col. 1). Cocrystals occur from noncovalent interactions between multiple species (pg. 1444, Col. 2). Solid solutions form where there are substantial similarities between crystal structures and packing (pg. 1444, Col. 2). Moynihan teaches impurity occurrence and removal in crystalline products from process reactions (title). Moynihan teaches that the generation of impurities during process chemistry and crystallization, is part of the reality of manufacturing pharmaceuticals. FDA guidelines designate organics, inorganics, and residual solvents as likely impurities, wherein organic impurities can arise from starting materials, byproducts, intermediates, degradation products, reagents, solvents, ligands, catalysts, stereoisomers, and filter aids (pg. 689. Col. 1): PNG media_image3.png 244 487 media_image3.png Greyscale (pg. 702). Moynihan teaches that many impurities are satisfactorily removed by washing, recrystallization, or reslurrying. However, some impurities are not adequately removed by these processes, in which case adjustment of the reaction or extraction steps may be necessary (pg. 701, Col. 2, “Conclusions”). It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the crystallization process of Liu to arrive at ethanol and/or retinol (i.e., fermentative residues), and/or retinyl acetate (i.e., FARE), as instant component (2), to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because: -Liu teaches its final product in the form of a crystal, - Urwin teaches that perfect separation with optimal productivity, yield, and purity is very difficult to achieve, and that despite its high selectivity, in crystallization, unwanted impurities routinely contaminate a crystallization product (abstract), -Moynihan teaches impurities in crystal products as arising from residual solvent, starting products, intermediates, byproducts, degradation products, and more, and -Liu teaches ethanol as a solvent, retinyl acetate as a starting product, and retinol as an intermediate, - Moynihan teaches that many impurities are satisfactorily removed by washing, recrystallization, or reslurrying, but that some impurities are not adequately removed by these processes, in which case adjustment of the reaction or extraction steps may be necessary. In view of the solvent, starting product, and intermediate of Liu, an ordinary skilled artisan would reasonable expect ethanol, retinyl acetate, and/or retinol as impurities in its crystal. Moreover, in view of the teachings of Moynihan, an ordinary skilled artisan would have the skill to modify the amounts and the composition of particulate impurities by routine washing, recrystallization, reslurrying, and/or adjustment of reaction or extraction steps. Thus, an ordinary skilled artisan would have been motivated to minimize impurities to arrive at a crystalline retinyl palmitate product with maximized purity and yield, and hence potency for pharmacological or cosmetic use. Since Liu teaches a crystal comprising about 97.3% retinyl palmitate, the ratio of retinoid component to fermentative residue, is met. Regarding the 0.15 to 1.5wt.% of the FARE, in view of the teachings of Moynihan, which state that chemical techniques are known in the art to modify and minimize the amount of impurities, an ordinary skilled artisan would have been motivated to minimize the amount of starting product, i.e., retinyl acetate, as an impurity in the final retinyl palmitate crystal, and "[W]here 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." MPEP 2144.05(II). The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. Note: The phrases “fermentative” in reference to “residue” and “carbon source,” and the phrase “bio-based” in reference to carbon, in claims 1-3, 12, 24, 37, and 40, are interpreted as product-by-process limitations. Product-by-Process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps; once a product appearing to be substantially identical is found and a prior art rejection is made, the burden shifts to the applicant to show a nonobvious difference (MPEP 2113). As such, the ethanol, retinol, and retinyl acetate taught by Liu meets the limitation of both “a fermentative residue” and “a fermentation carbon source thereof,” and the components of the crystal of Liu meet the limitations of “bio-based carbon.” Regarding claims 2 and 23, ethanol is a fermentation carbon source (see [063] of the instant specification). Regarding claim 3, 40, 42, since the combination of Liu, Urwin, and Moynihan teaches the instantly claimed composition of claim 1, these limitations are met. See MPEP 2112.01, Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989). Regarding claims 4 and 5, retinyl palmitate meets the limitations of formula (I) when R is -CH2OR2, and R2 is alkanoyl. Regarding claim 12, retinyl acetate is a FARE. Regarding claim 21, since the composition does not comprise farnesol, the limitation of claim 21 is met. Regarding claim 24, Liu teaches a crystal comprising about 97.3% retinyl palmitate. In view of the teachings of Urwin and Moynihan, which state that chemical techniques are known in the art to modify and minimize the amount of impurities, an ordinary skilled artisan would have been motivated to minimize the amount of residual solvent, i.e., ethanol, and "[W]here 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." MPEP 2144.05(II). The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. Regarding claim 34, Liu teaches 99% all-trans-retinyl palmitate. Regarding claim 36, Lu teaches a crystal comprising about 97.3% retinyl palmitate, wherein the ratio of 97.3:2.7, which falls within the instantly claimed range. If the 2.7% contains components that are not FARE or fermentation carbon source, Urwin and Moynihan teach that chemical techniques are known in the art to modify and minimize the amount of impurities. As such, an ordinary skilled artisan would have been motivated to minimize the amount of fermentative residue in Liu to arrive at a product with an optimized amount of retinyl palmitate; "[W]here 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." MPEP 2144.05(II). The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. (New) Claims 14 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (Efficient two-step chemo-enzymatic synthesis of all-trans-retinyl palmitate with high substrate concentration and product yield, App Microbio and Biotech, published 2015, IDS of 07/24/2024), Urwin (A structured Approach to Cope with Impurities during Industrial Crystallization Development, OPR&D, published 202, PTO-892) and Moynihan (Impurity Occurrence and Removal in Crystalline Products from Process Reactions, OPR&D, published 2017, PTO-892), as applied to claims 1-5, 12, 21, 23-24, 34, 36, 40, and 42 above, and further in view of WO 2022/195013 to Reynaud (published 09/2022, IDS of 07/30/2024) and Choi (Microbial Production of Retinyl Palmitate and Its Application as a Cosmeceutical. Antioxidants, published 2020, PTO-892), Li (The multifaceted nature of retinoid transport and metabolism, HepatoBiliary Surg Nutr; published 2014, PTO-892). Liu, Urwin, and Moynihan are applied as discussed above and incorporated herein. Regarding claim 37, while the combination of Liu, Urwin, and Moynihan teaches the composition of instant claim 1, it differs from that of instant claim 37 in that it does not teach retinyl acetate as the retinoid component. Reynaud teaches a process for preparing a retinol composition, to prevent oxidation of retinol and enhance oxidative stability (title, abstract), wherein the process preferably produces 99% or 99.5% trans-retinol (pg. 4, lines 18-21). Reynaud teaches that the term retinol includes retinyl palmitate, retinyl acetate, and others (pg. 4, lines 22-25). Reynaud teaches that retinol may be obtained, through chemical synthesis or the use of biotechnology, such as fermentation (pg. 2, lines 4-8). Reynard teaches that the step of isolating retinol from the process may be achieved by an means known in the art (pg. 12, lines 17-19). Reynaud teaches that the culture/fermentation process can be easily adjusted and used by a person skilled in the art according to the microorganism (pg. 9, lines 24-25). Choi teaches that retinyl acetate can be produced from retinol (pg. 2, Fig. 1). It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the reaction process of Liu, to produce an all-trans-retinyl acetate product, from the retinol, to arrive at instant claim 37. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because: -Choi teaches that both retinyl palmitate and retinyl acetate can be produced from retinol, -Liu teaches a process of making retinyl palmitate from retinol, and -Li teaches all-trans forms as natural ligands for specific retinoic acid receptors, such as RARalpha, beta and gamma, that affect essential physiological processes (pg. 126). As such, an ordinary skilled artisan would have been motivated to make such a modification to predictably arrive at an all-trans-retinyl acetate that is optimized for to target RARalpha, beta, or gamma retinoic acid receptors. Regarding claim 14, since, as taught by Choi, retinyl palmitate and retinyl acetate are both retinyl esters that are known in the art as produced in chemical or formation reactions from retinol, an ordinary skilled artisan would reasonably expect retinyl palmitate to be a byproduct in a reaction producing retinyl acetate, since a) Urwin teaches that perfect separation with optimal productivity, yield, and purity is very difficult to achieve, and that despite its high selectivity, in crystallization, unwanted impurities routinely contaminate a crystallization product (abstract), b) Moynihan teaches impurities in crystal products as arising from residual solvent, starting products, intermediates, byproducts, degradation products, and more, c) retinyl palmitate can be a biproduct of reaction with retinol. (New) Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Liu (Efficient two-step chemo-enzymatic synthesis of all-trans-retinyl palmitate with high substrate concentration and product yield, App Microbio and Biotech, published 2015, IDS of 07/24/2024), Urwin (A structured Approach to Cope with Impurities during Industrial Crystallization Development, OPR&D, published 202, PTO-892) and Moynihan (Impurity Occurrence and Removal in Crystalline Products from Process Reactions, OPR&D, published 2017, PTO-892), as applied to claims 1-5, 12, 14, 21, 23-24, 34, 36, 40, and 42 above, and further in view of Egberg (Determination of all-trans and 13-cis Vitamin A in Food Products by High Pressure Liquid Chromatography, J. Agric. Food Chem., published 1977, PTO-892) Liu II (Targeting Particle Size Specification in Pharmaceutical Crystallization, OPR&D, published 11/2022, PTO-892) Liu, Urwin, and Moynihan are applied as discussed above and incorporated herein. While the combination of Liu, Urwin, and Moynihan teaches the composition of instant claim 1, it differs from that of instant claim 44 in that it does not teach particle size. Egberg teaches the determination of all-trans and 13-cis Vitamin A by high pressure liquid chromatography, in food products, such as vitamins (title, abstract; pg. 1127). Egberg teaches a vitamin a product with a particle size of 0.05-0.2mm, which is 50-200µm (pg. 1129, Col. 1). Liu II teaches targeting particle size specification in pharmaceutical crystallization (title). Liu II teaches that the goal of crystallization process in the pharmaceutical industry is to isolate the drug substances and intermediates as solid materials with targeted product attributes. Particle size is a common critical quality attribute of a drug substance as it affects downstream processability and drug release characteristics. A series of techniques have been applied for the prediction and control of particle size. A large particle size (greater than 250 µm) can be the targeted quality attribute for a drug compound. Large particles generally have good flowability and avoid the issues created by small particles. For a crystallization process targeting a large particle size, optimizing process parameters involve understanding and controlling the underlying mechanisms, such as nucleation and growth. For a seeded cooling crystallization in batch, the main parts include optimizing the cooling profile and a seeding strategy. Agitation is also critical to the final product particle size distribution (pgs. A-B, Introduction). In summary, Liu II teaches that interplay between nucleation, growth, breakage, and agglomeration significantly influence particle size distribution. A combination of proper techniques and optimized parameters result in a target particle size distribution (pg. J, Conclusion). It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the particle size of the combined crystals of Liu, Urwin, and Moynihan, to arrive at instant claim 44. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because: - Egberg teaches vitamin A products with a particle size of 0.05-0.2mm, which is 50-200µm, and -Liu II teaches that large particles have good flowability, and that it is known in the crystallization art to modify nucleation, growth, breakage, and/or agglomeration to optimize target particle size distribution. As such, an ordinary skilled artisan would have been motivated to make such a modification, to predictably arrive at a crystallized retinyl acetate composition with a particle size optimized for a targeted use in a drug or food product. Conclusion No claims are allowed. 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30. 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, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. 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. /LAUREN WELLS/Examiner, Art Unit 1622
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Prosecution Timeline

Dec 04, 2023
Application Filed
Jul 10, 2024
Examiner Interview (Telephonic)
Jul 23, 2024
Non-Final Rejection — §103, §112
Oct 24, 2024
Response Filed
Nov 04, 2024
Final Rejection — §103, §112
Apr 30, 2025
Request for Continued Examination
May 02, 2025
Response after Non-Final Action
Jul 09, 2025
Non-Final Rejection — §103, §112
Dec 16, 2025
Response Filed
Feb 27, 2026
Final Rejection — §103, §112
Apr 07, 2026
Response after Non-Final Action

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5-6
Expected OA Rounds
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Grant Probability
99%
With Interview (+57.8%)
2y 11m
Median Time to Grant
High
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Based on 213 resolved cases by this examiner. Grant probability derived from career allow rate.

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