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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) via Application No. JP2022-148363, however, no certified copy has been filed.
The effective filing date is September 16th, 2022.
Status of Claims
Claims 1-11 are currently pending and examined on the merits.
Information Disclosure Statement
The information disclosure statements received September 6th , 2023 and March 25th, 2024 have been considered.
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 1-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more.
Step 2A, Prong 1
In accordance with MPEP § 2106, claims found to recite statutory subject matter (claims 1-10 are drawn to a method, claim 11 is drawn to a system) (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 (reasonings in [brackets]):
Claims 1 states:
a molecular simulation execution unit that executes a molecular simulation on each of the initial conformations set by the initial conformation setting unit…[which is a mental step, i.e. can be performed with pen and paper]
a solubility feature calculation unit that calculates a solubility feature based on an execution result of the molecular simulation performed by the molecular simulation execution unit…[mathematical calculation]
a partial three-dimensional structural information acquisition unit that
calculates partial three-dimensional structural information indicating one or multiple three- dimensional partial structures of the molecule with respect to each of the molecular simulation…[mathematical calculation]
a partial structure specification unit that specifies the partial structure corresponding to variation in the solubility feature, based on the solubility feature calculated by the solubility feature calculation unit and the partial three-dimensional structural information calculated by the partial three-dimensional structural information acquisition unit…[which is a mathematical concept of a mathematical calculation]
a thermodynamic stability evaluation unit that…evaluates thermodynamic stability for each of the group…[which is a mental step, i.e., can be performed with pen and paper]
a variation determination unit that … causes the initial conformation setting unit to set multiple new initial conformations…[mental step]
an output unit that…outputs an evaluation result of solubility based on the solubility feature used to calculate the variation…[mental step]
Claim 2 states:
the molecular simulation execution unit uses molecular dynamics simulation…[mathematical calculation]
Claim 6 states:
…the partial structure specification unit specifies the partial structure by a regression analysis…[mathematical calculation]
Claim 7 states:
the partial structure specification unit performs statical analysis using an average value of distribution of dihedral angles as an explanatory variable, or performs the regression analysis by machine learning, and specifies the partial structure based on the distribution of the dihedral angles correlated with the solubility feature…[mathematical calculation]
Claim 8 states:
the variation evaluation unit selects the group that is evaluated…[mental step]
Claim 9 states:
the initial conformation setting unit sets multiple new initial conformations by adding…[mental step]
Claims 10 and 11 state:
executing a molecular simulation on each of the set initial conformations…[mental step]
calculating a solubility feature based on an execution result of the molecular simulation…[mathematical concept]
calculating partial three-dimensional structural information indicating one or multiple three-dimensional partial structures of the molecule with respect to each of the molecular simulation…[mathematical concept]
specifying the partial structure corresponding to variation in the solubility feature, based on the solubility feature and the partial three-dimensional structural information…[mental step]
classifying the solubility feature based on the specified partial structure, evaluating thermodynamic stability for each of the group…[mental step]
selecting one or some of the groups based on the evaluation…[mental step]
calculating variation in the solubility feature in the selected group…[mathematical concept]
by setting multiple new initial conformations…[mental step]
executing a process of executing the molecular simulation …[mental step]
calculating the solubility feature …[mathematical concept]
calculating the partial three-dimensional structural information…[mathematical concept]
specifying the partial structure …[mental step]
evaluating the thermodynamic stability…[mental step]
and calculating the variation, based on the new initial conformations…[mathematical concept]
The claims recite an abstract idea of molecular dynamics simulations (See MPEP 2106.07(a)).
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 mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas.
There are no additional limitations that indicate that these claims require anything other than carrying out the recited mental process or mathematical concept 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 if falls within the “Mental processes” grouping of abstract ideas. As such, claim(s) 1-18 recite(s) an abstract idea/law of nature/natural phenomenon (Step 2A, Prong 1: YES).
Step 2A, Prong 2
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). This judicial exception is not integrated into a practical application because the claims do not recite additional elements that reflects an improvement to technology or applies or uses the recited judicial exception to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment. Specifically, the claims recite the following additional elements:
Claim 1 states:
a molecular simulation execution unit
a solubility feature calculation unit
a partial three-dimensional structural information acquisition unit
a partial structure specification unit
a thermodynamic stability evaluation unit
a variation determination unit
an output unit
Claim 2 states: the molecular simulation execution unit
Claim 3 states: the solubility feature calculation unit
Claims 4-6 state: the partial three-dimensional structural information acquisition unit
Claim 7 states: the partial structure specification unit
Claim 8 states: the variation evaluation unit
Claim 9 states: the initial conformation setting unit
There are no limitations that indicate that the claimed analysis engine or the formats of the provided data require anything other than generic computing systems. As such, these limitations equate 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. As such, claims 1-18 is/are directed to an abstract idea/law of nature/natural phenomenon (Step 2A, Prong 2: 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 because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment. The instant claims recite the following additional elements:
Claim 1 states:
a molecular simulation execution unit
a solubility feature calculation unit
a partial three-dimensional structural information acquisition unit
a partial structure specification unit
a thermodynamic stability evaluation unit
a variation determination unit
an output unit
Claim 2 states: the molecular simulation execution unit
Claim 3 states: the solubility feature calculation unit
Claims 4-6 state: the partial three-dimensional structural information acquisition unit
Claim 7 states: the partial structure specification unit
Claim 8 states: the variation evaluation unit
Claim 9 states: the initial conformation setting unit
Regarding claims 1-11, The steps of obtaining sequencing and/or training data and performing sample collection do not integrate the abstract idea into a practical application and constitutes an insignificant extra-solution activity (i.e., data gathering and presentation), which does not impose a meaningful limit on the abstract idea. As discussed above, there are no additional limitations to indicate that the claimed analysis engine 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. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims.
Furthermore, the additional elements recited in the claims amount to well-understood, routine and conventional activity, as evidenced by Huimin Zhu et al. (Journal of Molecular Liquids 338 (2021) 116731. Pg. 1-7) who teaches a machine learning based simulation of an anti-cancer drug (busulfan) solubility in supercritical carbon dioxide: ANFIS model and experimental validation.
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 1-11 are not patent eligible.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-5, 8, 10 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pavel Klimovich et al. (J Comput Aided Mol Des (2010) 24:307–316.) in view of Alan Grossfield et al. (Living J Comput Mol Sci. 2018 ; 1(1) pg. 1-45) and in further view of T. P. Straatsma et al. (J. Chem. Phys. 90, 3300–3304 (1989)).
Regarding claims 1, 10, and 11 Klimovich et al. teaches a computational method of predicting hydration free energy using molecular dynamics simulations and multiple starting conformations (Abstract, pg.307-308, re: clm. 1, 10, 11 …A solubility evaluation device [method][ non-transitory computer-readable recording medium having stored therein a solubility evaluation program that causes a computer to execute a process, the process comprising], comprising…).
Klimovich et al. further teaches an initial conformation setting initial conformations of a molecule on pg. 314, which discloses multiple starting conformations (“we used multiple starting conformations to assess convergence…”) (Methods, re: clm. 1, 10, 11, …an initial conformation setting unit that sets multiple different initial conformations with a molecule…a molecular simulation execution unit that executes a molecular simulation on each of the initial conformations set by the initial conformation setting unit…[… setting multiple different initial conformations with a molecule…])
Klimovich et al. further teaches the hydration free energy, which reads on the solvation free energy in water, as supported by the applicant’s disclosure in the specification (Abstract, pg. 307; Spec, para. 0033; re: clm. 1, 10, 11 …a solubility feature calculation unit that calculates a solubility feature based on an execution result of the molecular simulation performed by the molecular simulation execution unit…[ specifying the partial structure corresponding to variation in the solubility feature, based on the solubility feature and the partial three-dimensional structural information…])
Klimovich et al. further teaches the torsion governing the orientation of the hydroxyl hydrogen and the accounting for said torsion within the simulation on pg. 312, Fig. 4, and further in a 3D model in Fig. 5 (re: clm. 1, …a partial three-dimensional structural information acquisition unit that calculates partial three-dimensional structural information indicating one or multiple three-dimensional partial structures of the molecule with respect to each of the molecular simulation…[… calculating partial three-dimensional structural information indicating one or multiple three-dimensional partial structures of the molecule with respect to each of the molecular simulation…].)
Klimovich et al. further discloses that the hydroxyl hydrogen conformation depends on the environment on pg. 312, which reads on variation (re: clm. 1,10, 11 …a partial structure specification unit that specifies the partial structure corresponding to variation in the solubility feature, based on the solubility feature calculated by the solubility feature calculation unit and the partial three-dimensional structural information calculated by the partial three-dimensional structural information acquisition unit…[… specifying the partial structure corresponding to variation in the solubility feature, based on the solubility feature and the partial three-dimensional structural information…].)
Klimovich et al. further teaches setting multiple new initial conformations in response to a target variation value as disclosed in the case of d-xylose, which Klimovich et al. teaches required a conformation-specific technique on pg. 313 (re: clm. 1, …a variation determination unit that, when the variation calculated by the variation evaluation unit is equal to or greater than a target variation value, causes the initial conformation setting unit to set multiple new initial conformations…)
Klimovich et al. further teaches reporting of a solubility feature with respect to conformation variation evaluation (re: clm. 1,10,11 …an output unit that, when the variation calculated by the variation evaluation unit is less than the target variation value, outputs an evaluation result of solubility based on the solubility feature used to calculate the variation in such a case…[… when the calculated variation is equal to or greater than a target variation value, by setting multiple new initial conformations, executing a process of executing the molecular simulation, calculating the solubility feature, calculating the partial three-dimensional structural information,...][… calculating the solubility feature, calculating the partial three-dimensional structural information, …])
Klimovich et al. does not explicitly disclose a thermodynamic stability evaluation (re: clm. 1,10, 11 …a thermodynamic stability evaluation unit that, by creating a group by classifying the solubility feature based on the partial structure specified by the partial structure specification unit, evaluates thermodynamic stability for each of the group…[ by creating a group by classifying the solubility feature based on the specified partial structure, evaluating thermodynamic stability for each of the group…])
Klimovich et al. does not explicitly disclose selection of a molecular group based upon thermodynamic stability (re: clm. 1,10, 11, …a variation evaluation unit that selects one or some of the groups based on the evaluation by the thermodynamic stability evaluation unit and that calculates variation in the solubility feature in the selected group…[… by selecting one or some of the groups based on the evaluation, calculating variation in the solubility feature in the selected group…][… evaluating the thermodynamic stability, and calculating the variation…][…and calculating the variation, based on the new initial conformations…])
Klimovich et al. does not explicitly disclose logic-based changes to evaluation determination (re: clm. 1, 10, 11…a variation determination unit that, when the variation calculated by the variation evaluation unit is equal to or greater than a target variation value, causes the initial conformation setting unit to set multiple new initial conformations…[… calculating the variation, based on the new initial conformations;..][… when the calculated variation is less than the target variation value, outputting an evaluation result of solubility based on the solubility feature used to calculate the variation in such a case…])
Grossfield et al. discloses best practices for molecular simulations, including a checklist detailing best practices for sampling metrics on pg. 8. This reads on conditional practices for variations during molecular simulations (re: clm. 1, 10, 11, …a variation evaluation unit that selects one or some of the groups based on the evaluation by the thermodynamic stability evaluation unit and that calculates variation in the solubility feature in the selected group…[… by selecting one or some of the groups based on the evaluation, calculating variation in the solubility feature in the selected group…][… evaluating the thermodynamic stability, and calculating the variation…][…and calculating the variation, based on the new initial conformations…]))
Grossfield et al. further discloses procedures for computing a confidence interval on pg. 22 as it relates to the number of particular observations in a simulation, further details nonparametric bootstrapping on pg. 27 (sampling with replacement (selectively) based upon the relationship between a metric of interest in a simulation, and further discloses replica exchange molecular dynamics on pg. 31 which detail thermodynamic condition changes which reads on selecting a group based on features of said simulation (re: clm. 1, 10, 11, …a variation evaluation unit that selects one or some of the groups based on the evaluation by the thermodynamic stability evaluation unit and that calculates variation in the solubility feature in the selected group…[…by selecting one or some of the groups based on the evaluation, calculating variation in the solubility feature in the selected group…][… evaluating the thermodynamic stability, and calculating the variation…][…and calculating the variation, based on the new initial conformations…])
Grossfield et al. does not disclose a thermodynamic stability evaluation, specifically, nor directly integrates thermodynamic stability evaluations in molecular dynamics evaluations explicitly (re: clm. 1,10, 11 , …a variation evaluation unit that selects one or some of the groups based on the evaluation by the thermodynamic stability evaluation unit and that calculates variation in the solubility feature in the selected group…[…by selecting one or some of the groups based on the evaluation, calculating variation in the solubility feature in the selected group…][… evaluating the thermodynamic stability, and calculating the variation…][…and calculating the variation, based on the new initial conformations…])
Straatsma et al. teaches thermodynamic integration in molecular dynamics simulations (Title, Abstact, Introduction, pg. 3300; re: clm. 1, 10, 11 …a variation evaluation unit that selects one or some of the groups based on the evaluation by the thermodynamic stability evaluation unit and that calculates variation in the solubility feature in the selected group…[…by selecting one or some of the groups based on the evaluation, calculating variation in the solubility feature in the selected group…][… evaluating the thermodynamic stability, and calculating the variation…)
In KSR Int 'l v. Teleflex, the Supreme Court, in rejecting the rigid application of the teaching, suggestion, and motivation test by the Federal Circuit, indicated that “The principles underlying [earlier] cases are instructive when the question is whether a patent claiming the combination of elements of prior art is obvious. When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR Int'l v. Teleflex lnc., 127 S. Ct. 1727, 1740 (2007).
Applying the KSR standard to Klimovich et al. , Grossfield et al. and Straatsma et al., the examiner finds that the combination of predicting hydration free energies in dynamics simulations as taught by Klimovich et al. with the best practices for molecular simulations as taught by Grossfield et al. and the treatment of rotational isomers in free energy evaluations inclusive of dihedral angles represents some teaching, suggestion or motivation in the prior art that would have lead one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
One of ordinary skill in computational chemistry would have been motivated to combine the teachings of Klimovich et al. , Grossfield et al. and Straatsma et al.. as the combination would produce a stronger molecular dynamics simulation method.
One of ordinary skill in computational chemistry would have success in combining the teachings of Klimovich et al. , Grossfield et al. and Straatsma et al. as all arts exist in the same field (computational chemistry). Therefore, the invention would have been prima facie obvious to one of skill in the art at the time of filing of the application, absent evidence to the contrary.
Regarding claims 2-4, Klimovich et al. teaches a molecular dynamics simulation (Title, re: clm. 2, … wherein the molecular simulation execution unit uses molecular dynamics simulation...), solvation free energy (“This manuscript reports the results of a blind test of hydration free energy calculations, re: clm. 3, … the solubility feature calculation unit uses solvation free energy as a solubility feature…), and uses partial three-dimensional structural information and structures related to an angle via the use of dihedral angles as disclosed in Fig. 4 (re: clm. 4, … wherein, as partial three-dimensional structural information, the partial three-dimensional structural information acquisition unit uses a three-dimensional structure relating to an angle…). Klimovich et al. teaches the limitations of claims 2-4.
Regarding claim 5, Straatsma et al. teaches in equation 15 on pg. 3302 the probability density of the dihedral angle in a simulation of molecular stability (re: clm. 5, … clm. 5, … wherein, as the partial three-dimensional structural information, the partial three-dimensional structural information acquisition unit uses distribution of dihedral angles…). Straatsma et al. teaches the limitations of claim 5.
Regarding claim 8, Klimovich teaches on pg. 313, Fig. 6 and 7 computed hydration free energies and concludes on pg. 314 that “Overall, these results further support the notion that physical force fields can make accurate predictions of fundamental thermodynamic properties in favorable cases…” (re: clm. 8, … wherein the variation evaluation unit selects the group that is evaluated by the thermodynamic stability evaluation unit to be most thermodynamically stable.) As Straatsma et al. explicitly teaches thermodynamic integration in molecular dynamics simulations, one of ordinary skill in the art would be motivated to combine the teachings of Straatsma et al. with the teachings of Klimovich et al to improve the dynamics simulation. One of ordinary skill in the art would find success in combining as both arts exist in the same field of invention. Therefore, the combination teaches the limitations of claim 8.
Claim(s) 6-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Klimovich et al. in view of Grossfield et al. and Straatsma et al. as applied to claims 1-5, 8, 10 and 11 above in view of Tohid N. Borhani et al. (Phys.Chem.Chem.Phys., 2019, 21, 13706-13720).
Klimovich et al. in view of Grossfield et al. and Straatsma et al. is applied to claims 1-5, 8, 10 and 11 above.
Klimovich et al. in view of Grossfield et al. and Straatsma et al. does not teach a regression analysis nor machine learning as applied to partial structure prediction (re: clm. 6, … the partial structure specification unit specifies the partial structure by a regression analysis in which the partial three-dimensional structural information is used as an explanatory variable and the solubility feature is used as an objective variable… re: clm. 7, … performs the regression analysis by machine learning, and specifies the partial structure based on the distribution of the dihedral angles correlated with the solubility feature…)
Regarding claim 6, Borhani et al. teaches a regression analysis applied to predicting solvation free energies, stating in the abstract (pg. 13706) “…we propose two quantitative structure property relationships (QSPRs) to predict the Gibbs free energy of solvation, developed using partial least squares (PLS) and multivariate linear regression (MLR) methods for 295 solutes in 210 solvents with total number of data points of 1777.”(re: clm. 6, … the partial structure specification unit specifies the partial structure by a regression analysis in which the partial three-dimensional structural information is used as an explanatory variable and the solubility feature is used as an objective variable…)
Regarding claim 7, Borhani et al. teaches artificial neural networks may be used to predict quantitative structure property relationships on pg. 13708 (re: clm. 7, … r performs the regression analysis by machine learning, and specifies the partial structure based on the distribution of the dihedral angles correlated with the solubility feature by machine learning, and specifies the partial structure based on the distribution of the dihedral angles correlated with the solubility feature…)
Borhani et al. does not explicitly disclose a dihedral angle feature analysis (re: clm. 7, … performs the regression analysis by machine learning, and specifies the partial structure based on the distribution of the dihedral angles correlated with the solubility feature…)
Applying the KSR standard to Klimovich et al. , Grossfield et al., Straatsma et al., and Borhani et al. the examiner finds that the combination of predicting hydration free energies in dynamics simulations as taught by Klimovich et al. with the best practices for molecular simulations as taught by Grossfield et al., the treatment of rotational isomers in free energy evaluations inclusive of dihedral angles as taught by Straatsma et al., and the regression analysis and machine learning as applied to quantitative structure property relationships as disclosed by Borhani et al. represents some Teaching, suggestion or motivation in the prior art that would have lead one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
One of ordinary skill in computational chemistry would have been motivated to combine the teachings of to Klimovich et al. , Grossfield et al., Straatsma et al., and Borhani et al. as the combination would produce a stronger molecular dynamics simulation method.
One of ordinary skill in computational chemistry would have success in combining the teachings of to Klimovich et al. , Grossfield et al., Straatsma et al., and Borhani et al. as all arts exist in the same field (computational chemistry). Therefore, the invention would have been prima facie obvious to one of skill in the art at the time of filing of the application, absent evidence to the contrary.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Klimovich et al. in view of Grossfield et al., Straatsma et al., and Borhani et al. as applied to claims 1-8, 10 and 11 above in view of David Mobley et al. ( J Chem Theory Comput. 2007;3(4):1231–1235.)
Klimovich et al. in view of Grossfield et al., Straatsma et al., and Borhani et al. is applied to claims 1-8, 10 and 11 above.
Regarding claim 9, Klimovich et al. in view of Grossfield et al., Straatsma et al., and Borhani et al. teaches performing molecular dynamics simulations in view of alternate molecular conformations as disclosed by the confine-and-release calculations applied to d-xylose at different conformation states taught by Klimovich et al. pg. 312 (and in the statement on pg. 309, “We also found that d-xylose has two substantially different (and slow to interconvert) ring conformations... We were able to compute the free energy landscape for altering the pucker…”) This reads on the additional initial conformation of a molecular state( re: clm. 9, … wherein the initial conformation setting unit sets multiple new initial conformations … the group selected by the variability evaluation unit…).
Klimovich et al. in view of Grossfield et al., Straatsma et al., and Borhani et al. does not explicitly teach adding conformations specifically in regard to belonging to a group selected in view of structure variability (re: clm. 9 ,… by adding an additional initial conformation belonging to the group selected by the variability evaluation unit, to the initial conformations.)
Mobley et al. teaches two molecular metastable states, apo and holo, and applies a general “confine-and-release” framework for free energy calculations that accounts for free energies occurring during state change, which reads on molecules within a group (either apo or holo) and the re-application of molecular dynamics calculation in view of said group (re: clm. 9, … initial conformation belonging to the group selected by the variability evaluation unit…)
Applying the KSR standard to Klimovich et al. , Grossfield et al., Straatsma et al., Borhani et al. and Mobley et al., the examiner finds that the combination of predicting hydration free energies in dynamics simulations as taught by Klimovich et al. with the best practices for molecular simulations as taught by Grossfield et al., the treatment of rotational isomers in free energy evaluations inclusive of dihedral angles as taught by Straatsma et al., the regression analysis and machine learning as applied to quantitative structure property relationships as disclosed by Borhani et al. and the conformational state grouping of Mobley et al. represents some Teaching, suggestion or motivation in the prior art that would have lead one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
One of ordinary skill in computational chemistry would have been motivated to combine the teachings of to Klimovich et al. , Grossfield et al., Straatsma et al., Borhani et al. and Mobley et al. as the combination would produce a stronger molecular dynamics simulation method. In support of this motivation, Mobley et al.’s method is disclosed by Klimovich et al.
One of ordinary skill in computational chemistry would have success in combining the teachings of to Klimovich et al. , Grossfield et al., Straatsma et al., Borhani et al. and Mobley et al. as all arts exist in the same field (computational chemistry). Therefore, the invention would have been prima facie obvious to one of skill in the art at the time of filing of the application, absent evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN T STUBBS whose telephone number is (571)272-0340. The examiner can normally be reached M-F 8-5 EST.
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/J.T.S./Examiner, Art Unit 1686
/LARRY D RIGGS II/ Supervisory Patent Examiner, Art Unit 1686
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