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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 1/28/2026 has been entered and considered. Rejections and/or objections not reiterated from the previous office action mailed 10/29/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Status of the Claims
Claims 17, 20, and 22-23 are pending and under consideration in this action. Claims 16, 18-19, and 21 were canceled in the amendment filed 1/28/2026.
Priority
This application is a CON of U.S. 17/269,766, filed 02/19/2021, which is a U.S. national phase application PCT/JP2019/032722, filed 08/21/2019. PCT/JP2019/032722 claims priority from Japanese Application No. JP2018-154760, filed 08/21/2018, as reflected in the filing receipt mailed on 08/31/2021. Acknowledgment is made of applicant' s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The claims to the benefit of priority are acknowledged and the effective filing date of claims 17, 20, and 22-23 is 08/21/2018.
Claim Objections
Claims 17 and 22 are objected to because of the following informalities:
Claims 17 and 22 recite the phrases “predicting a critical degree of supersaturation (ScT,x)” and “a critical degree of supersaturation Sc(T,x)” in lines 2 and 4 of the claims, respectively. The critical degree of supersaturation should be abbreviated as either “(ScT,x)” or “Sc(T,x)” for consistency.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 17, 20, and 22-23 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.
Claims 17 and 22 recite the phrase “wherein the predicting of the critical degree of supersaturation comprises a step of inputting data including information based on descriptors on a compound obtained as a spherulite and at least one of information based on descriptors on a solvent used for crystallization and a solution temperature during crystallization into a predictive model of a critical degree of supersaturation required to obtain the spherulite of the compound, and outputting a predictive value of a critical degree of supersaturation from the predictive model” in lines 18-23 of the claims. The metes and bounds of the claim are rendered indefinite due to the lack of clarity. The Specification discloses that the predictive model can use principal component analysis (PCA) followed by partial least squares regression (PLSR) (Example 18, Para. [0166]-[0171] and Example 32, Para. [0185]-[0195]) or an unmodified AlexNet in which the outer layer is replaced by Support Vector Regression (Example 33, Para. [0196]). The limitation recites steps of inputting data and outputting a predictive value. However, it is unclear what parameters are necessary such that the model operates to provide the output predictive critical degree of supersaturation using, for example PCA+PLSR. Therefore, the metes and bounds of the invention are not clearly defined. Clarification of the metes and bounds of the claims through clearer claim language is respectfully requested. Claims 20 and 23 are also rejected due to their dependency from claims 17 and 22.
Claims 17 and 22 also recite the limitations “predicting a critical degree of supersaturation (ScT,x) required to obtain a spherulite of a compound” and “determining, based on the following equation: a critical degree of supersaturation Sc(T,x) = C*/Cs, a concentration C* to be achieved…” in lines 2-6 of the claims. The metes and bounds of the claim are rendered indefinite due to the lack of clarity. It is unclear whether the critical degree of supersaturation predicted in the “predicting” step is used in the formula in the “determining” step. The specification (see Para. [0043]) discloses that the “critical degree of supersaturation" in the method of the present invention may be an actual measured value obtained by the measurement method described herein or a predictive value outputted from the predictive model of a critical degree of supersaturation described herein. Recitation of “said critical degree of supersaturation” or “the critical degree of supersaturation” in the “determining” step would use the critical degree of supersaturation from the “predicting” step. However, as claimed, “a critical degree of supersaturation” recited in the “determining” could be the measured or predicted value, rendering the metes and bounds of the claim unclear. Claims 20 and 23 are also rejected due to their dependency on claims 17 and 22.
Claims 17 and 22 also recite the phrase “a concentration C* to be achieved in a mixed solvent system having the solvent ratio x of the predetermined good solvent and the predetermined poor solvent” in lines 5-6 of the claim. The terms “good solvent” and “poor solvent” in claims 17 and 22 are relative terms which renders the claim indefinite. The terms “good solvent” and “poor solvent” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification (see at least Para. [0048]-[0051]) discloses that the supersaturated solution can be prepared by dissolving the compound in a good solvent, and changing the ratio of good solvent to poor solvent for crystallization. However, the specification does not provide, for example, any parameters defining a good solvent vs. a poor solvent for a respective compound. Claims 20 and 23 are also rejected due to their dependence from claims 17 and 22.
Claims 17 and 22 also recite the limitations “having the solvent ratio x of the predetermined good solvent and the predetermined poor solvent” and “…while maintaining or relaxing the supersaturated state” in lines 5-6 and 17 of the claims, respectively. There is insufficient antecedent basis for this limitation in the claim, since there is no prior mention of this “the solvent ratio”, “the predetermined good solvent”, “the predetermined poor solvent”, and “the supersaturated state” earlier in the claim. This rejection can be overcome by amendment of claims 17 and 22 to recite “having a solvent ratio x of a predetermined good solvent and a predetermined poor solvent” and “…while maintaining or relaxing a supersaturated state”. Claims 20 and 23 are also rejected due to their dependence from claims 17 and 22.
Applicant is kindly reminded that any amendment must find adequate support in the Specification as originally filed.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 17, 20, and 22-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite both (1) mathematical concepts (mathematical relationships, formulas or equations, or mathematical calculations) and (2) mental processes, i.e., concepts performed in the human mind (including observations, evaluations, judgements or opinions) (see MPEP § 2106.04(a)).
Step 1:
In the instant application, claims 17, 20, and 22-23 are directed towards a process, which falls into one of the categories of statutory subject matter (Step 1: YES).
Step 2A, Prong One:
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong One). The following instant claims recite limitations that equate to one or more categories of judicial exceptions:
Claims 17 and 22 recite a mathematical concept (i.e., using a model to predict a critical degree of supersaturation; it is noted that the model could combine principal component analysis with partial least squares regression (see example 18, Para. [0166]-[0171])) in “predicting a critical degree of supersaturation (ScT,x) required to obtain a spherulite of a compound, wherein the predicting of the critical degree of supersaturation comprises a step of inputting data including information based on descriptors on a compound obtained as a spherulite and at least one of information based on descriptors on a solvent used for crystallization and a solution temperature during crystallization into a predictive model of a critical degree of supersaturation required to obtain the spherulite of the compound, and outputting a predictive value of a critical degree of supersaturation from the predictive model”; and a mathematical concept in “determining, based on the following equation: a critical degree of supersaturation Sc(T,x) = C*/Cs, a concentration C* to be achieved in a mixed solvent system having the solvent ratio x of the predetermined good solvent and the predetermined poor solvent, wherein Cs is a measured solubility depending on a temperature T and a solvent ratio x, C* is a concentration to be achieved at a temperature T and the solvent ratio x, and the solvent ratio x is a ratio of a predetermined good solvent to a predetermined poor solvent”.
Claims 20 and 22 recite a mental process (i.e., a judgement of descriptors to include in the model) in “wherein the descriptors are selected from the group consisting of constitutional indices, Ring descriptors, topological indices, walk and path counts, …, 2D Monte Carlo descriptors, 3D Monte Carlo descriptors, quantum-chemical descriptors, and combinations thereof”.
These recitations are similar to the concepts of collecting information, and displaying certain results of the collection and analysis is Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)), and organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships.
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification, and are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Specifically, the steps recited in claims 17 and 22 involve nothing more than determining a critical degree of supersaturation using a predictive model and performing a calculation using a formula. The step reciting “using a predictive model” is, under the BRI, performed using mathematical operations. The instant Specification (see example 18, Para. [0166]-[0171]) discloses that the predictive model combines principal component analysis with partial least squares regression. Therefore, the claimed steps are not further defined beyond something that reads on performing calculations using a computer as a tool. As such, said steps are directed to judicial exceptions. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application (Step 2A, Prong One: YES).
Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). The following independent claims recite limitations that equate to additional elements:
Claim 17 recites “dissolving a solute at a concentration that does not cause nucleation based on a solubility in the good solvent to prepare a solution”; “adding the poor solvent to the solution and controlling an amount of the solvent such that an overall concentration of the solution becomes equal to or greater than the concentration C* to be achieved”; and “precipitating and growing spherulites while maintaining or relaxing the supersaturated state”.
Claim 22 recites “dissolving a solute at a concentration that does not cause nucleation, based on a solubility in a mixed solvent having a solvent ratio x, to prepare a solution”; “adding an acid, a base, or an inorganic salt to the solution and controlling an amount of solvent such that an overall concentration of the solution becomes equal to or greater than the target concentration C*”; and “precipitating and growing spherulites while maintaining or relaxing the supersaturated state”.
Regarding the above cited limitations in claims 17 and 22 of (i) dissolving a solute at a concentration that does not cause nucleation based on a solubility in the good solvent / in the mixed solvent having solvent ratio x, to prepare a solution (claims 17 and 22); (ii) adding the poor solvent to the solution and controlling an amount of the solvent such that an overall concentration of the solution becomes equal to or greater than the concentration C* to be achieved (claim 17); (iii) precipitating and growing spherulites while maintaining or relaxing the supersaturated state (claims 17 and 22); and (iv) adding an acid, a base, or an inorganic salt to the solution and controlling an amount of solvent such that an overall concentration of the solution becomes equal to or greater than the target concentration C* (claim 22). These limitations equate to extra-solution activity steps because the limitations are recited at a high level of generality to physically produce the spherulite of a compound. The instant claim steps recite nothing more than data gathering using routine laboratory elements. The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity (see MPEP 2106.05(d)(II)): determining the level of a biomarker in blood by any means (Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017)); and detecting DNA or enzymes in a sample (Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017)).
Additionally, as described above under 112(b) rejections above, since it is unclear if the critical degree of supersaturation in the predicting step is used in the subsequent steps, the recited limitations (i)-(iv) do not incorporate all uses of the recited judicial exceptions (see MPEP § 2106.05(f)). As such, claims 17, 20, and 22-23 are directed to an abstract idea (Step 2A, Prong Two: NO).
Step 2B:
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The instant independent claims recite the same additional elements described in Step 2A, Prong Two above.
Regarding the above cited limitations in claims 17 and 22 of (i) dissolving a solute at a concentration that does not cause nucleation based on a solubility in the good solvent / in the mixed solvent having solvent ratio x, to prepare a solution (claims 17 and 22); (ii) adding the poor solvent to the solution and controlling an amount of the solvent such that an overall concentration of the solution becomes equal to or greater than the concentration C* to be achieved (claim 17); (iii) precipitating and growing spherulites while maintaining or relaxing the supersaturated state (claims 17 and 22); and (iv) adding an acid, a base, or an inorganic salt to the solution and controlling an amount of solvent such that an overall concentration of the solution becomes equal to or greater than the target concentration C* (claim 22). These limitations when viewed individually and in combination, are WURC limitations as taught by Beck et al. (Polycrystalline growth in precipitation of an aromatic amine derivative and l-glutamic acid. J. Crystal Growth. 311(2): 320-326 (2009); provided in the IDS dated 1/2/2024). Beck et al. teaches a method to investigate the effect of supersaturation and temperature on the particle morphology of l-glutamic acid and an aromatic amine derivative, which form various crystal types including spherulites (Abstract). Beck et al. further discloses that both l-glutamic acid and the secondary aromatic amine derivative were dissolved in distilled water before precipitation was initiated by a pH shift with an equimolar amount of 17 wt.% HCl (limitation (i), (ii), and (iv)) (Pg. 321, Col. 2, Para. 2). Beck et al. further discloses that spherulitic growth can be found in samples of the aromatic amine at higher initial supersaturation ratios a few minutes after nucleation (limitation (iii)) (Pg. 325, Col. 1, Para. 2 and Pg. 325, Fig. 11).
Additionally, the above cited limitations in claims 17 and 20 of (i) preparing a solution, (ii) adding solvent to a solution, (iii) precipitating spherulite crystals, and (iv) adding acid/base/salt to a solution are well-understood, routine and conventional laboratory techniques. The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity (see MPEP 2106.05(d)(II)): determining the level of a biomarker in blood by any means (Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017)); and detecting DNA or enzymes in a sample (Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017)).
These additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the instant claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 17, 20, and 22-23 are not patent eligible.
Response to Arguments under 35 U.S.C. 101
Applicant’s arguments filed 1/28/2026 have been fully considered but they are not persuasive.
1. Applicant argues that as amended, the pending claims are directed to methods that go beyond merely outputting a predicted critical degree of supersaturation. Specifically, the claims now require technical operations, including: (1) determining a critical degree of supersaturation based on a formula; (2) dissolving a solute at a concentration that does not cause nucleation, based on its solubility in the good solvent, to prepare a solution; (3) adding the poor solvent to the solution and controlling the amount of the solvent; and (4) precipitating and growing spherulites while maintaining or relaxing the supersaturated state. Accordingly, the amended claims recite specific technical steps, and therefore the claims as a whole include limitations that amount to significantly more than any purported abstract idea (Applicant’s Remarks, Pg. 6-7). Applicant’s arguments are not persuasive for the following reasons:
MPEP 2106.04(d)(II) recites:
The analysis under Step 2A Prong Two is the same for all claims reciting a judicial exception, whether the exception is an abstract idea, a law of nature, or a natural phenomenon (including products of nature). Examiners evaluate integration into a practical application by: (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception(s); and (2) evaluating those additional elements individually and in combination to determine whether they integrate the exception into a practical application, using one or more of the considerations introduced in subsection I supra, and discussed in more detail in MPEP §§ 2106.04(d)(1), 2106.04(d)(2), 2106.05(a) through (c) and 2106.05(e) through (h).
Regarding, the limitation of “determining a critical degree of supersaturation based on a formula”, identified by Applicant as (1) above, has been identified as a judicial exception in Step 2A, Prong One above. The integration of a judicial exception into a practical application can only be achieved by additional elements, not by a limitation that recites a judicial exception. Thus, the recited limitation is not considered as an improvement in reproducible production of spherulites.
Additionally, regarding limitations (2), (3), and (4) noted by Applicant above, this limitations were identified as additional elements in Step 2A, Prong Two above. Analysis under Step 2A, Prong Two above shows that these limitations equate to insignificant extra-solution activity that do not incorporate all uses of the recited judicial exceptions. Further analysis in Step 2B above shows that these limitations are well-understood, routine and conventional activities as taught by Beck et al. When viewed individually or as an ordered combination, these limitations do not comprise an inventive concept and therefore do not amount to significantly more than the judicial exception. This argument is thus not persuasive.
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.
Claims 17, 20, and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Beck et al. (Polycrystalline growth in precipitation of an aromatic amine derivative and l-glutamic acid. J. Crystal Growth. 311(2): 320-326 (2009); published 11/17/2008; provided in the IDS dated 1/2/2024) in view of Wicker et al. (Will it crystallise? Predicting crystallinity of molecular materials. CrystEngComm. 17(9): 1927-1934 (2015); published 11/4/2014; provided in the IDS dated 6/7/2022; previously cited).
Regarding claim 17, Beck et al. teaches a method to investigate the effect of supersaturation and temperature on the particle morphology of l-glutamic acid and an aromatic amine derivative, which form various crystal types including spherulites (i.e., a method for producing spherulites of a compound) (Abstract). Beck et al. further teaches that increasing the initial supersaturation leads to exclusively to spherulites of the β-polymorph and a more compact morphology characterized by smaller crystalline subunits. Open-structured polycrystalline particles were formed at intermediate (S0=6) values of the initial supersaturation, whereas higher initial supersaturation ratios (S0=8) ratios produced fully developed and more compact spherulites (Pg. 324, Col. 2, Para. 2). The initial supersaturation values for a given substance can be predicted using the following formula: Si,0=C0/Ci* (Pg. 322, Col. 2, Para. 5). Beck et al. does not disclose that the supersaturation values are critical supersaturation values. However, the instant Specification discloses that the critical degree of supersaturation is the minimum degree of supersaturation required to obtain a spherically-shaped crystal of a compound (Para. [0011]). Therefore, it would be obvious to one of ordinary skill in the art to predict the critical degree of supersaturation (i.e., the minimum degree of supersaturation required for spherulite growth) using the formula provided by Beck et al., since increasing the initial supersaturation leads to exclusively to spherulites (i.e., predicting a critical degree of supersaturation (ScT,x) required to obtain a spherulite of a compound and a predictive value of a critical degree of supersaturation). Beck et al. further teaches the calculation of the initial supersaturation (Si,0) based on the initial concentration (C0) of the dissolved substance and the solubility (Ci*) using the following equation: Si,0=C0/Ci* (Pg. 322, Col. 2, Para. 5). Beck et al. does not disclose that the supersaturation calculation is used to for the critical degree of supersaturation. However, Beck et al. discloses that spherulitic growth of l-glutamic acid particles occurs at high initial supersaturation ratios, in accordance with previous studies (Pg. 323, Col. 1, Para. 2). In view of the disclosure in the instant Specification, as described above (Para. [0011]), it would be obvious to one of ordinary skill in the art that the critical degree of supersaturation necessary to obtain a spherulite is in the upper range of the initial supersaturation ratios and Beck et al. teaches the calculation of supersaturation required to obtain a spherulite of a compound (i.e., determining, based on the following equation: a critical degree of supersaturation Sc(T,x) = C*/Cs, a concentration C* to be achieved). Beck et al. further teaches that the compounds were dissolved in distilled water, and that 17 wt.% HCl was used for precipitation of the spherulite (i.e., in a mixed solvent system having the solvent ratio x of the predetermined good solvent and the predetermined poor solvent; C* is a concentration to be achieved at the solvent ratio x; and the solvent ratio x is a ratio of a predetermined good solvent to a predetermined poor solvent) (Pg. 321, Col. 2, Para. 1). The crystallization conditions and temperatures are shown in Table 2 (i.e., C* is a concentration to be achieved at the temperature T and the solvent ratio x) (Pg. 323, Table 2). Beck et al. further teaches that solubility values for the aromatic amine were measured by UV spectroscopy in distilled water at temperatures of 5, 25 and 60 °C (i.e., Cs is a measured solubility depending on a temperature T and a solvent ratio x) (Pg. 322, Col. 2, Para. 2). Beck et al. further teaches that both l-glutamic acid and the secondary aromatic amine derivative were dissolved in distilled water before precipitation was initiated by a pH shift (i.e., dissolving a solute at a concentration that does not cause nucleation based on a solubility in the good solvent to prepare a solution) (Pg. 321, Col. 2, Para. 2). Beck et al. further teaches that the compounds were precipitated by a pH shift with an equimolar amount of 17 wt.% HCl (i.e., adding the poor solvent to the solution and controlling an amount of the solvent such that an overall concentration of the solution becomes equal to or greater than the C* to be achieved) (Pg. 321, Col. 2, Para. 2). Beck et al. further teaches that spherulitic growth can be found in samples of the aromatic amine at higher initial supersaturation ratios a few minutes after nucleation. Fig. 11(a) shows initial and undeveloped spherulites with branches radiating from the center, while Fig. 11(b) shows spherulitic patterns in one of a broken particle (i.e., precipitating and growing spherulites while relaxing the supersaturated state) (Pg. 325, Col. 1, Para. 2 and Pg. 325, Fig. 11). Beck et al. further teaches that l-glutamic acid and the secondary aromatic amine derivative were used (i.e., information based on descriptors on a compound obtained as a spherulite) (Pg. 321, Col. 2, Para. 2).
Regarding claim 22, Beck et al. teaches the limitations of predicting a critical degree of supersaturation (ScT,x) required to obtain a spherulite of a compound; determining, based on the following equation: a critical degree of supersaturation Sc(T,x) = C*/Cs, a concentration C* to be achieved in a mixed solvent system having the solvent ratio x of the predetermined good solvent and the predetermined poor solvent, wherein Cs is a measured solubility depending on a temperature T and a solvent ratio x, C* is a concentration to be achieved at the temperature T and the solvent ratio x, and the solvent ratio x is a ratio of a predetermined good solvent to a predetermined poor solvent; dissolving a solute at a concentration that does not cause nucleation, based on a solubility in a mixed solvent having a solvent ratio x, to prepare a solution; precipitating and growing spherulites while maintaining or relaxing the supersaturated state; and inputting data including information based on descriptors on a compound obtained as a spherulite as described for claim 17 above. Beck et al. further teaches that the compounds were precipitated by a pH shift with an equimolar amount of 17 wt.% HCl (i.e., adding an acid, a base, or an inorganic salt to the solution and controlling an amount of solvent such that an overall concentration of the solution becomes equal to or greater than the target concentration C*) (Pg. 321, Col. 2, Para. 2).
Beck et al. does not teach wherein the predicting of the critical degree of supersaturation comprises a step of inputting data including at least one of information based on descriptors on a solvent used for crystallization and a solution temperature during crystallization into a predictive model, and outputting a predictive value from the predictive model (claims 17 and 22) and wherein the descriptors are selected from the group consisting of constitutional indices, Ring descriptors, topological indices, walk and path counts, …, 2D Monte Carlo descriptors, 3D Monte Carlo descriptors, quantum-chemical descriptors, and combinations thereof. (claims 20 and 23).
Regarding claims 17 and 22, Wicker et al. teaches a machine learning approach to predict and control the crystallinity of molecular materials (Abstract). The greater the number of rotatable bonds a molecule has, the more conformationally flexible that molecule is, which means it will have a large number of potential conformers in equilibrium in solution. This effective dilutes the concentration of the desired conformer, decreasing the degree of supersaturation, and therefore its crystallization tendency (i.e., predicting a critical degree of supersaturation) (Pg. 1931, Col. 2, Para. 2). Wicker et al. further teaches that three different machine learning models were trained using 177 RDKit descriptors of drug-like molecules (i.e., comprises a step of inputting data including information based on descriptors on a compound) (Pg. 1930, Col. 1, Para. 2 and 4). Wicker et al. further teaches the impact of solvent on the (re)crystallization conditions of the com pounds and its impact on the predictive accuracy of the model (i.e., at least one of information based on descriptors on a solvent used for crystallization into a predictive model) (Pg. 1932, Col. 1, Para. 4 - Col. 2, Para. 3). Wicker et al. further teaches that the output of the machine learning algorithm includes a value for "crystalline" vs. "non-crystalline" (i.e., outputting a predictive value from the predictive model) (Pg. 1929, Col. 1, Para. 6).
Regarding claims 20 and 23, Wicker et al. teaches that the descriptors for the model include rotatable bond count, zero order molecular, valence connectivity index, ring count, number of heteroatoms, and number of radical electrons (i.e., wherein the descriptors are selected from the group consisting of: geometrical descriptors, connectivity indices, molecular properties, ring descriptors, information indices, functional group counts, and charge descriptors) (Pg. 1931, Col. 1, Para. 2-3 and Supporting Information, Pg. 2, Table 1).
Therefore, regarding claims 17, 20, and 22-23, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of producing spherulites of a compound of Beck et al. with the machine learning model predicting the crystallinity of compounds of Wicker et al. because one of the key features dominating the propensity to crystallize is the rotatable bond count, which in turn affects the degree of supersaturation. Additionally, since the algorithm outputs a score, it can be applied to guide synthetic derivatization of target molecules in order to increase crystallinity as desired (i.e., to achieve the spherulites of Beck et al.) (Wicker et al., Pg. 1932, Col. 2, Para. 5 - Pg. 1933, Col. 1, Para. 2 and Pg. 1931, Col. 2, Para. 2). One of ordinary skill in the art would be able to combine the teachings of Beck et al. with Wicker et al. with reasonable expectation of success due to the same nature of the problem to be solved, since both are drawn towards a method of predicting the crystallinity of compounds. Therefore, regarding claims 17, 20, and 22-23, the instant invention is prima facie obvious (MPEP § 2142).
Response to Arguments under 35 U.S.C. 103
Applicant’s arguments filed 1/28/2026 have been fully considered but they are not persuasive.
1. Applicant argues that the disclosure of Toldy relates to nucleation probability, not to predicting a critical degree of supersaturation required for spherulite formation, as recited in the pending claims. Toldy neither discloses nor teaches a critical degree of supersaturation required for spherulite formation. Accordingly, Toldy fails to provide any teaching or suggestion relevant to the claimed prediction of a critical degree of supersaturation for obtaining spherulites, and there is no technical basis or motivation for combining Toldy with Wicker in the manner asserted by the Examiner to arrive at the claimed subject-matter with any reasonable expectation of success (Applicant’s Remarks, Pg. 7-8). Applicant’s arguments are not persuasive for the following reasons:
Applicant’s arguments regarding the obviousness of the claims over Wicker et al. in view of Toldy et al., as failing to teach the claimed prediction of a critical degree of supersaturation for obtaining spherulites, as in amended claims 17 and 22 have been considered but they are not persuasive in view of the new grounds of rejection that relies on a new combination of references as necessitated by claim amendment (Applicant’s remarks, Pg. 7-8).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 17, 20, and 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 20 of copending Application No. 17/296,766 in view of Beck et al. (Polycrystalline growth in precipitation of an aromatic amine derivative and l-glutamic acid. J. Crystal Growth. 311(2): 320-326 (2009); provided in the IDS dated 1/2/2024).
Claims 17 and 22 of the instant application and claim 1 of copending Application No. 17/269,766 are directed towards a method for producing a spherulite of a compound. Instant claims 17 and 22 and copending claim 1 include a step for predicting the critical degree of supersaturation for a compound using a predictive model, including steps of: (1) inputting data including information on the compound obtained as a spherulite and information on the solvent/solution temperature using descriptors (the descriptors in the instant case are in dependent claims 18 and 23), and (2) outputting a predictive value of the critical degree of supersaturation. Instant claims 17 and 22 and copending claim 1 also include steps of preparing the supersaturated solution and precipitating the spherulite of the compound.
Instant claims 17 and 22 differ from copending claim 1 in the step of preparing the supersaturated solution. The instant claims recite steps of (a) dissolving a solute at a concentration that does not cause nucleation based on a solubility in the good solvent to prepare a solution and (b) adding the poor solvent to the solution and controlling an amount of the solvent such that an overall concentration of the solution becomes equal to or greater than the concentration C* to be achieved (claim 17) or (b) adding an acid, a base, or an inorganic salt to the solution and controlling an amount of solvent such that an overall concentration of the solution becomes equal to or greater than the target concentration C* (claim 22), while the copending claim 1 recites a step of preparing a supersaturated solution of the compound having a degree of supersaturation equal to or higher than a critical degree of supersaturation required to obtain the spherulite of the compound. The instant claims are a species of the genus recited in copending claim 1. However, Beck et al. discloses that both l-glutamic acid and the secondary aromatic amine derivative were dissolved in distilled water before precipitation was initiated by a pH shift with an equimolar amount of 17 wt.% HCl (i.e., steps (a) and (b) of instant claims 17 and 22) (Pg. 321, Col. 2, Para. 2).
It would have been obvious to one of ordinary skill in the art to modify the method of copending claim 1 to include the specific method of preparing a supersaturated solution of the compound as in the method of Beck et al., because the method of Beck et al. enables the ability to control the spherulite morphology (Beck et al., Abstract and Pg. 326, Col. 1, Para. 2). Accordingly, instant claims 17, 20, and 22-23 are not patentably distinct from copending claims 1 and 20 of Application No. 17/296,766.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DIANA P SANFORD whose telephone number is (571)272-6504. The examiner can normally be reached Mon-Fri 8am-5pm EST.
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, Karlheinz Skowronek can be reached at (571)272-9047. 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.
/D.P.S./Examiner, Art Unit 1687
/Lori A. Clow/Primary Examiner, Art Unit 1687