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 .
Applicant's response filed 7/31/2026 has been fully considered. The following rejections
and/or objections are either reiterated or newly applied.
Status of Claims
Claims 1, 5-7, 9-10, 13, and 15-20 pending and examined on the merits.
Claims 2-4, 8, 11-12, and 14 cancelled.
Priority
The instant application filed on 6/14/2021 claims the benefit of priority to U.S. Provisional Patent Application No. 63/039,872 filed on 6/16/2020. Thus, the effective filing date of the claims is 6/16/2020.
The applicant is reminded that amendments to the claims and specification must comply with 35 U.S.C. § 120 and 37 C.F.R. § 1.121 to maintain priority to an earlier-filed application. Claim amendments may impact the effective filing date if new subject matter is introduced that lacks support in the originally filed disclosure. If an amendment adds limitations that were not adequately described in the parent application, the claim may no longer be entitled to the priority date of the earlier filing.
Claim Objections
The objection to claims 1, 19, and 20 withdrawn in view of Applicant's claim amendments and remarks filed on 7/31/2026.
Withdrawn Rejections
35 USC § 112(b)
The rejection of claims 1, 19, and 20 under 35 USC 112(b) withdrawn in view of Applicant's claim amendments and remarks filed on 7/31/2026. However, newly made rejections under 35 USC 112(b) necessitated by claim amendments are applied below.
35 USC § 112(d)
The rejection of claim 14 under 35 USC 112(d) withdrawn (and is moot) in view of Applicant's cancellation of the claim in amendments filed on 7/31/2026.
35 USC § 103
The rejection of claims 1, 5-7, 9-10, 13, and 15-20 under 35 USC 103 withdrawn in view of Applicant's amendments and remarks filed on 7/31/2026. Examiner has fully considered these arguments and found them persuasive. Specifically, Applicant asserts that "Mackerell does not teach or suggest the specific hybrid resolution approach in which a first (higher) spatial resolution grid is used for nonionic solvent molecules (e.g. water) and a second (lower) spatial resolution grid is used for ionic solvent molecules" (Remarks 7/31/2026 pages 17-18). Applicant also asserts that "Nguyen's voxel sums and state-difference calculations are not performed in the context of separate high/low resolution grids for nonionic vs. ionic species with cross-term sampling in both" (Remarks 7/31/2026 page 18). Applicant further asserts that Meier "does not teach the specific MD-based hybrid gridding for explicit non-ionic + inion solvents, VDoS entropy extraction tied to the hybrid grids, or the volume-constrained intra-voxel feature for ions" (Remarks 7/31/2026 page 18). Finally, Applicant asserts that "interactions between the simulated nonionic solvent molecules and the simulated ionic solvent molecules are sampled in both the first and second spatial resolutions and pair-wise additive contributions are attributed equally" is not taught or suggested by any reference or combination (Remarks 7/31/2026 pages 18-19). The closest prior art is considered to be Mackerell, Nguyen, and Meier as discussed in the Office Action filed 4/6/2026.
While Mackerell discloses using multiple grid resolutions for simulations, these calculations are performed separately and there is no suggestion of "interactions between the simulated nonionic solvent molecules and the simulated ionic solvent molecules are sampled in both the first and second spatial resolutions and pair-wise additive contributions are attributed equally". Examiner also notes there is no explicit teaching or suggestion of "spatially resolved enthalpy contributions using pair-wise additive interactions between the simulated nonionic and ionic solvent molecules that are sampled in both the first and second spatial resolutions and attributing said contributions equally to the nonionic and ionic solvent molecules". Nguyen nor Meier remedy these deficiencies.
Claim Rejections - 35 USC § 112
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 1, 5-7, 9-10, 13, and 15-20 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 1, 19, and 20 now recite "pair-wise additive contributions" in the amended whereby clause. Further down in the "generating" step, the claims recite "determining spatially resolved enthalpy contributions using pair-wise additive interactions". The claims then recite "attributing said contributions". It is not clear if "said contributions" are referring to the "pair-wise additive contributions" (which are not required to be spatially resolved enthalpy contributions), the "spatially resolved enthalpy contributions", or both.
All other claims depend from claims 1, 19, and 20, and therefore are also rejected under 35 USC 112(b) as being indefinite.
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.
The rejection of claims 1, 5-7, 9-10, 13, and 15-20 under 35 USC 101 contains newly recited portions necessitated by claim amendments.
Claims 1, 5-7, 9-10, 13, and 15-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of a mental process, a mathematical concept, organizing human activity, or a law of nature or natural phenomenon without significantly more. 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 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1, 19, and 20: “defining [. . .] a plurality of three-dimensional (3D) grids of voxels on at least a portion of two or more simulated target molecules solvated with simulated solvent molecules to produce a 3D simulation structure wherein the simulated solvent molecules comprise one or more simulated nonionic solvent molecules and one or more simulated ionic solvent molecules, wherein at least two of the simulated target molecules form a complex with one another, wherein a first 3D grid of the plurality of 3D grids comprises a first spatial resolution, which first 3D grid comprises at least some of the simulated nonionic solvent molecules, wherein a second 3D grid of the plurality of 3D grids comprises a second spatial resolution that differs from the first spatial resolution, which second 3D grid comprises at least some of the simulated ionic solvent molecules” provides for organizing information (defining grids of voxels involves sorting or structuring data) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“the first and second spatial resolutions are selected as part of atomistic molecular dynamics (MD) simulations in an explicit solvent environment to obtain an equivalent set of continuous statistics per voxel despite a concentration of the simulated nonionic solvent molecules being higher than a concentration of the simulated ionic solvent molecules in the 3D simulation structure” provides a comparison (selecting spatial resolutions to obtain equivalent statistics involves comparing statistics at various spatial resolutions) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“the second spatial resolution is selected such that a volume of a given simulated ionic solvent molecule is less than a volume of a given voxel in the second 3D grid” provides a comparison (selecting a spatial resolution that results in a volume being less than another involves comparing volumes at various spatial resolutions) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“wherein interactions between the simulated nonionic solvent molecules and the simulated ionic solvent molecules are sampled in both the first and second spatial resolutions and pair-wise additive contributions are attributed equally to the nonionic and ionic solvent molecules, thereby enabling accurate distinction of solute-nonionic, solute-ionic, nonionic-nonionic, ionic-ionic, and nonionic-ionic interactions in a generation of at least one 3D solvation free energy map” recites an intended use of the abstract idea (defining the 3D grids).
“determining one or more thermodynamic, dynamic, and/or structural parameters using the 3D simulation structure as part of one or more atomistic simulations comprising MD simulations, wherein the determining comprises averaging the parameters over time frames of the MD simulations” provides a mathematical calculation (determining parameters by averaging them over a time frame involves mathematical calculations) that is considered a mathematical concept, which is an abstract idea.
“determining spatially resolved enthalpy contributions using pair-wise additive interactions between the simulated nonionic and ionic solvent molecules that are sampled in both the first and second spatial resolutions and attributing said contributions equally to the nonionic and ionic solvent molecules” provides a mathematical calculation (determining spatially resolved enthalpy contributions using pair-wise additive interactions involves mathematical calculations) that is considered a mathematical concept, which is an abstract idea.
“determining spatially resolved entropy contributions using vibrational density of states (VDoS) obtained from Fourier transformed fluctuations of atomic velocities in the 3D simulation structure” provides a mathematical calculation (determining spatially resolved entropy contributions using vibrational density of states involves mathematical calculations) that is considered a mathematical concept, which is an abstract idea.
“determining a difference in solvation free energies” provides a mathematical calculation (determining a difference involves mathematical calculations) that is considered a mathematical concept, which is an abstract idea.
Claim 9: “identifying one or more at least potential binding sites on one or more of the simulated target molecules from the 3D solvation free energy map” provides an evaluation (identifying a potential binding site) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 10: “determining an impact of solvation on binding affinity between the simulated target molecules from the 3D solvation free energy map” provides an evaluation (determining solvation impact on binding affinity) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 16: “determining spatially resolved enthalpy and entropy contributions from the simulated nonionic solvent molecules and from the simulated ionic solvent molecules” provides an evaluation (determining enthalpy and entropy contributions) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 17: “distinguishing interactions between the simulated target molecules and the simulated nonionic solvent molecules, interactions between the simulated target molecules and the simulated ionic solvent molecules, interactions between the simulated nonionic solvent molecules, interactions between the simulated ionic solvent molecules, and interactions between the simulated nonionic solvent molecules and the simulated ionic solvent molecules from one another” provides an evaluation (distinguishing interactions between molecules) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
These recitations are similar to the concepts of collecting information, analyzing it, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), 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)) and 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)) that the courts have identified as concepts that can be practically performed in the human mind or are mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. Additionally, while claims 19 and 20 recite performing some aspects of the analysis on “A system, comprising at least one controller that comprises, or is capable of accessing, computer readable media comprising non-transitory computer-executable instructions” and “A computer readable media comprising non-transitory computer-executable instructions”, there are no additional limitations that indicate that this requires anything other than carrying out the recited mental processes or mathematical concepts in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it falls within the “Mental processes” grouping of abstract ideas. As such, claims 1, 5-7, 9-10, and 13-20 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). The judicial exceptions listed above are not integrated into a practical application because the claims do not recite an additional element or elements that reflects an improvement to technology. Specifically, the claims recite the following additional elements:
Claim 1, 19, and 20: “generating, by the computer, at least one 3D solvation free energy map from the set of simulation data, wherein generating the at least one 3D solvation free energy map [. . .] thereby producing the 3D solvation free energy map” provides insignificant extra-solution activities (outputting data visualization is a post-solution activity involving data manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 18: “sampling interactions between the simulated nonionic solvent molecules and the simulated ionic solvent molecules in both the first and second spatial resolutions” provides insignificant extra-solution activities (sampling interaction data a is a post-solution activity involving data gathering steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 19: “A system, comprising at least one controller that comprises, or is capable of accessing, computer readable media comprising non-transitory computer-executable instructions” provides insignificant extra-solution activities (running instructions on generic computer components) that do not serve to integrate the judicial exceptions into a practical application.
Claim 20: “A computer readable media comprising non-transitory computer-executable instructions” provides insignificant extra-solution activities (running instructions on generic computer components) that do not serve to integrate the judicial exceptions into a practical application.
The steps for visualizing and sampling data are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application because they are post-solution activities involving data gathering and manipulation steps (see MPEP 2106.04(d)(2)). Furthermore, the limitations regarding implementing program instructions do not indicate that they require anything other than mere instructions to implement the abstract idea in a generic way or in a generic computing environment. As such, this limitation equates to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. Therefore, claims 1, 5-7, 9-10, and 13-20 are directed to an abstract idea (Step 2A, Prong 2: NO).
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 because the claims recite additional elements that are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application, or equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment.
As discussed above, there are no additional elements to indicate that the claimed “A system, comprising at least one controller that comprises, or is capable of accessing, computer readable media comprising non-transitory computer-executable instructions” and “A computer readable media comprising non-transitory computer-executable instructions” requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. Additionally, the limitations for visualizing and sampling data are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application. Furthermore, no inventive concept is claimed by these limitations as they are well-understood, routine, and conventional.
The 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 claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1, 5-7, 9-10, and 13-20 are not patent eligible.
Response to Arguments under 35 USC § 101
Applicant’s arguments filed 7/31/2026 are fully considered but they are not persuasive.
Applicant asserts, regarding Step 2A Prong 1, that the "claims as amended recite a specific, non-abstract technological implementation that solves a concrete technical problem in the field of computer-implemented molecular dynamics simulation and solvation analysis" and that the "claims integrate any arguably abstract elements into a practical application and recite significantly more than any judicial exception", and goes on to cite several limitations of the independent claims they view as distinct from the claims in Electric Power Group or Digitech (Remarks 7/31 2026 page 13-14). Examiner notes again that the 'electronic post office' example explicitly mentions volume ("100s of billions of emails") as not factoring into whether or not claims may be performed by a human, mentally or with pen and paper, therefore the mere fact that the instant invention is processing millions of frames in a particular way is not grounds for patent-eligibility and "the nature of the computations" does not render them non-mental. Specifically, MPEP 2106.04(a)(2) III. C recites that "A Claim That Requires a Computer May Still Recite a Mental Process".
Applicant further asserts that the "claims are distinguishable from Ambry and Myriad (diagnostic methods reciting natural correlations or isolated DNA)" because "the [instant] claims are directed to an improved computer-implemented simulation method, not a law of nature or natural phenomenon (Remarks 7/31/2026 page 15). Examiner notes that there are no additional limitations that indicate that this requires anything other than carrying out the recited mental processes or mathematical concepts in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it falls within the “Mental processes” grouping of abstract ideas. Furthermore, it is important to keep in mind that an improvement in the abstract idea itself is not considered an improvement in technology (MPEP 2106.05(a) II).
Applicant asserts, regarding Step 2A Prong 2, that the "claims integrate any judicial exception into a practical application" by "providing a practical tool for identifying potential binding sties (claim 9) and determining solvation impact on binding affinity (claim 10) in drug design", and that the steps for "producing a 3D map" or "sampling interactions" are "not a mere field-of-use limitation or insignificant extra-solution activity" (Remarks 7/31/2026 page 15). Examiner notes that claims 9 and 10, and the cited steps have been identified above as an abstract idea or are part of an identified abstract idea, and therefore may not integrate a judicial exception into a practical application per MPEP 2106.05(a) II (as noted in the immediately preceding paragraph). Furthermore, Applicant asserts that the computing hardware is not the focus, rather "the specific, non-generic algorithm and data structures (hybrid 3D grids with volume- and concentration-aware resolution selection) are" (Remarks 7/31/2026 page 16). Examiner reiterates that it is important to keep in mind that an improvement in the abstract idea itself is not considered an improvement in technology (MPEP 2106.05(a) II).
Applicant asserts, regarding Step 2B, that the "claims recite an inventive concept that amounts to significantly more than any alleged judicial exception, whether considered individually or as an order combination" and that the "amended independent claims require a specific, non-WURC combination of technical features" (Remarks 7/31/2026 page 16). Further, Applicant asserts that the Examiner's characterization of the listed elements as judicial exceptions themselves (rather than additional elements) is incorrect (with no explanation as to how or why they are additional elements) (Remarks 7/31/2026 page 16). Examiner maintains that the listed elements on page 16 of the Applicant's Remarks 7/31/2026 are indeed judicial exceptions for the reasons indicated in the above relevant section.
Therefore, the rejection of claims 1, 19, and 20 under 35 USC 101 is maintained. All other claims depend from these independent claims; therefore, their rejection is likewise maintained.
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 TH REE-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 finaI action.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert A. Player whose telephone number is (571)272-6350. The examiner can normally be reached Mon-Fri, 8am-5pm.
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/R.A.P./Examiner, Art Unit 1686
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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