CTFR 17/836,250 CTFR 101607 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority This application 17/836,250 claims priority from foreign application JP2021-148849 filed on 09/13/2021. Thus, the effective filing date is 09/13/2021. 12-151 AIA 26-51 12-51 Status of Claims Claims 1-10 are pending. Claims 1-10 are amended. Claims 1-10 are rejected. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 1-10 are eligible under 35 U.S.C. 101 because the claimed invention integrates an abstract idea into a practical application by improving the use of a Ising device. Examiner finds applicant’s arguments and amendments persuasive. The rejection under 101 is withdrawn. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. Examiner finds the amendments and arguments of applicant persuasive as Wassenaar et al. does not use an Ising device. The rejection under 102 is withdrawn . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Wassenaar et al. ( Going Backward: A Flexible Geometric Approach to Reverse Transformation from Coarse Grained to Atomistic Models Tsjerk A. Wassenaar, Kristyna Pluhackova, Rainer A. Böckmann, Siewert J. Marrink, and D. Peter Tieleman Journal of Chemical Theory and Computation 2014 10 (2), 676-690 DOI: 10.1021/ct400617g) in view of Perdomo-Ortiz et al. (Perdomo-Ortiz, A.; Dickson, N.; Drew-Brook, M.; Rose, G.; Aspuru-Guzik, A. Finding Low-Energy Conformations of Lattice Protein Models by Quantum Annealing. Scientific Reports 2012 , 2 (1).). This is a new ground of rejection necessitated by amendments. Claim limitations are italicized . Regarding the limitations of independent claim 1, independent claim 9, independent claim 10, inputting, to the Ising device, a first cost arithmetic expression that does not make distinction between a L-form and a D-form of a plurality of amino acids to cause the Ising device to perform searching for, as an answer of a combinatorial optimization problem, a first arrangement of a plurality of amino acids included in a medium molecule based on a value of a first cost arithmetic expression, Wassenaar et al. teaches a peptide with 20 amino acids (i.e. a medium molecule) for which an arrangement is searched as an answer of a combinatorial optimization problem (i.e. energy minimization) based on a cost function (i.e. MARTINI energy force field terms), which cannot distinguish a L-form and D-form of amino acids (i.e. a single backbone bead in MARTINI) (pg. 682). The use of an Ising device is an obvious variant in view of Perdomo-Ortiz et al. Regarding the limitations of independent claim 1, independent claim 9, independent claim 10, inputting, to the Ising device, the first arrangement and a second cost arithmetic expression that makes distinction between the L-form and the D-form of the plurality of amino acids to cause the Ising device to perform searching for, as the answer of the combinatorial optimization problem, a second arrangement of the plurality of amino acids based on a value of the second cost arithmetic expressionb y setting the first arrangement as an initial arrangement in the searching of the second arrangement; and outputting the second arrangement. Wassenaar et al. teaches the CHARMM36 system (Figure 5, p. 684 and description thereof, p682) that allows allow placement of a particle cis, trans, out, or chiral with respect to a set of particles, as shown in Figure 1 (p. 678). The first stage is the generation of an atomistic starting structure from coarse-grained coordinates, which is followed by the second stage, consisting of the relaxation of the atomistic structure (p. 676). Examiner’s reasoning is minimization (corresponding to searching for a second arrangement etc. with an all-atom energy function, i.e. CHARMM36) is performed after back mapping (corresponding to the feature "setting the first arrangement as an initial arrangement"). CHARMM36 is able to give an energy difference for L and D- forms of amino-acid, since it represents chirality accurately.) and outputting the second arrangement (e.g. Fig 5, p684). The use of an Ising device is an obvious variant in view of Perdomo-Ortiz et al. Regarding the limitation of dependent claim 2 , the additional feature of inputting, to the Ising device, the second arrangement, a cost arithmetic expression, and changed constraint term arithmetic expression information obtained by changing a coefficient of a certain constraint term among a plurality of constraint terms that constrains an arrangement of the plurality of amino acids, to cause the Ising device to perform searching for, as the answer of the combinatorial optimization problem, a third arrangement of the plurality of amino acids by setting the second arrangement as an initial arrangement in the searching of the third arrangement and outputting the third arrangement when the third arrangement is different from the second arrangement, Wassenaar et al. teaches simulated annealing simulations of the back mapped system, which includes changing the constraint of the simulation temperature (a constraint term) (fig. 5, p. 684). Regarding the limitation of dependent claim 3, the changing of the coefficient of a certain constraint term includes lowering the coefficient of the certain constraint term the certain constraint term for the changed constraint term arithmetic expression information, Wassenaar et al. teaches simulated annealing simulations of the back mapped system, which includes changing the constraint of the simulation temperature (a constraint term) (fig. 5, p. 684). Regarding the limitation of dependent claim 4, the plurality of constraint terms includes that, when inputted to the Ising device, cause the Ising device to ensure that each of the plurality of amino acids included in the medium molecule exists at only one place in a lattice space, Wassenaar et al. teaches electrostatic interactions were calculated using particle-mesh Ewald (PME) summation. This is because all atom force-field based simulations, e.g. with CHARMM36, have only one representation of each amino acid. Thus, being at more than one place in a lattice space as, e.g., defined by the grid used for the PME approach for the electrostatic interactions in the simulations, is an intrinsic property of the topology in Wassenaar et al. (p. 681) Regarding the limitation of dependent claim 5 , the plurality of constraint terms includes constraint terms that, when inputted to the Ising device, cause the Ising device to ensure that each of the plurality of amino acids included in the medium molecule does not exist at a same lattice point, Wassenaar et al. teaches that Electrostatic interactions were calculated using particle-mesh Ewald (PME) summation". The reason therefor is that the non-bonded interactions in the all-atom simulations in Wassenaar et al. are treated via the PME approach, which is solved on a grid, i.e. lattice. This applies a constraint, namely the electrostatic repulsion term, which prevents two atoms to be in the same spot on the grid because the repulsion approaches infinity in such a case (p. 681). Regarding the limitation of dependent claim 6 , the plurality of constraint terms includes constraint terms that, when inputted to the Ising device, cause the Ising device to ensure that amino acids of the plurality of amino acids included in the medium molecule are interlinked in a certain sequence, Wassenaar et al. achieves this by the bonded terms of the applied force-field (p. 682, "CHARMM 36 system). Regarding the limitation of dependent claim 7, the plurality of constraint terms includes constraint terms that, when inputted to the Ising device, cause the Ising device to ensure that unlinked amino acids of the plurality of amino acids contained in the medium molecule do not exist in adjacent lattices , Wassenaar et al. teaches electrostatic interactions were calculated using particle mesh Ewald (PME) summation. Non-bonded interactions in all-atom simulations are treated via the PME approach, which is solved on a grid, i.e. lattice. This applies a constraint, namely the electrostatic repulsion term, which prevents two atoms to be in adjacent spots on the grid (typical grid spacing for PME being 0.01 nm) because the repulsion approaches infinity in such a case (p. 681). Regarding the limitation of dependent claim 8, the outputting the third arrangement includes when the third arrangement found by the Ising device based on the changed constraint term arithmetic expression information search in which the coefficient of the constraint terms is lowered at a k+1-th time is same as the third arrangement found by the Ising device based on the changed constraint term arithmetic expression information in which the coefficient of the constraint terms is lowered at a k-th time, outputting the third arrangement found by the Ising device based on the changed constraint term arithmetic expression information in which the coefficient of the constraint terms is lowered at a k-th time, a k being any integer , Wassenaar et al. has output according to a general convergence criterion with discrete time setup, which is anticipated by inter alia the minimizations or the last part of the simulated annealing procedure given (Figure 5, p.684 and the description thereof). Wassenaar et al. does not explicitly teach a non-transitory computer-readable storage medium storing a search program comprising instructions which, when executed by at least one computer coupled to an Ising device having a hardware configuration of a quantum computer, cause the that causes at least one computer to execute a process, the process comprising (Claim 1) a search method implemented by a computer coupled to an Ising device having a hardware configuration of a quantum computer, the search method comprising (Claim 9) a search device coupled to an Ising device having a hardware configuration of a quantum computer, the search device comprising (Claim 10) With respect to the limitations of Claims 1, 9, 10 , Perdomo-Ortiz et al. teaches implementation of quantum annealing for lattice protein folding problems (six different experiments up to 81 super conducting quantum bits). This first implementation of a biophysical problem paves the way towards studying optimization problems in biophysics and statistical mechanics using quantum devices (abstract, A non-transitory computer-readable storage medium storing a search program comprising instructions which, when executed by at least one computer coupled to an Ising device having a hardware configuration of a quantum computer, cause the that causes at least one computer to execute a process, the process comprising (Claim 1), a search method implemented by a computer coupled to an Ising device having a hardware configuration of a quantum computer, the search method comprising (Claim 9), a search device coupled to an Ising device having a hardware configuration of a quantum computer, the search device comprising (Claim 10)) A person of ordinary skill in the art would combine Wassenaar et al. with Perdomo-Ortiz et al. as both works are in the same field of endavor finding stable confirmations of molecules. All Perdomo-Ortiz et al. adds is the use of an Ising device in order to optimize simulations. A person of ordinary skill in the art would be motivated to attempt methods that worked well on traditional computers on an Ising device. There is a reasonable expectation of success because all components work separately therefore, they will work when combined as the method is not changing. In addition, the actually steps of Wassenaar et al. are not changing it is just being run on an Ising device as taught by Perdomo-Ortiz et al. which farther gives a reasonable expectation of success. Response to Arguments Examiner finds applicant’s arguments filed on 3/23/2026 and amendments persuasive as the claimed invention integrates an abstract idea into a practical application by improving the use of a Ising device. Claims 1-10 are eligible under 101 and the rejection is withdrawn. Applicant’s arguments filed on 3/23/2026 with respect to the rejections of claims 1-10 under 102 have been fully considered and are persuasive. Therefore, the rejection under 102 has been withdrawn . However, upon further consideration, a new ground of rejection is made under 103 of Wassenaar et al. in view of Perdomo-Ortiz et al . In addition, applicant's arguments filed 3/23/2026 have been fully considered but they are not persuasive regarding the argument “ Wassenaar also does not disclose the claimed two-stage cost- expression system: it neither distinguishes a first cost arithmetic expression that does not distinguish between L-form and D-form amino acids from a second cost arithmetic expression that does make that distinction, nor teaches that the first cost arithmetic expression is obtained from the second by omitting a term representing the L/D difference so as to reduce the number of bits required for the combinatorial optimisation problem on the Ising device. Wassenaar does not disclose that, in a first stage, the hardware searches based on the simplified first cost arithmetic expression to obtain a first arrangement of the amino acids, and that, in a second stage, the hardware searches using the full second cost arithmetic expression that distinguishes L- and D-forms, with the first arrangement being used as an initial arrangement for the second-stage search, and outputs the resulting second arrangement .” Examiner states that Wassenaar et al. teaches the CHARMM36 system (Figure 5, p. 684 and description thereof, p682) that allows allow placement of a particle cis, trans, out, or chiral with respect to a set of particles, as shown in Figure 1 (p. 678). The first stage is the generation of an atomistic starting structure from coarse-grained coordinates, which is followed by the second stage, consisting of the relaxation of the atomistic structure (p. 676). Examiner’s reasoning is minimization (corresponding to searching for a second arrangement etc. with an all-atom energy function, i.e. CHARMM36) is performed after back mapping (corresponding to the feature "setting the first arrangement as an initial arrangement"). CHARMM36 is able to give an energy difference for L and D-forms of amino-acid, since it represents chirality accurately.) and outputting the second arrangement (e.g. Fig 5, p684). The use of an Ising device is an obvious variant in view of Perdomo-Ortiz et al. Examiner agrees that Wassenaar et al. does not teach “ the first cost arithmetic expression is obtained from the second by omitting a term representing the L/D difference so as to reduce the number of bits required for the combinatorial optimisation problem on the Ising device.” However, the omitting of a term is not in the claimed language and under the broadest reasonable interpretation omitting a term is not required and a different function can be used. Therefore, Wassenaar et al. teaches the use of an initial cost function to get an initial structure and then refining that structure with a second function and is prior art on the broadest reasonable interpretation of the claim. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Connor Beveridge whose telephone number is 571-272-2099. The examiner can normally be reached Monday - Thursday 9 am - 5 pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, 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. /C.H.B./Examiner, Art Unit 1687 /Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687 Application/Control Number: 17/836,250 Page 2 Art Unit: 1687 Application/Control Number: 17/836,250 Page 3 Art Unit: 1687 Application/Control Number: 17/836,250 Page 4 Art Unit: 1687 Application/Control Number: 17/836,250 Page 5 Art Unit: 1687 Application/Control Number: 17/836,250 Page 6 Art Unit: 1687 Application/Control Number: 17/836,250 Page 7 Art Unit: 1687 Application/Control Number: 17/836,250 Page 8 Art Unit: 1687 Application/Control Number: 17/836,250 Page 9 Art Unit: 1687 Application/Control Number: 17/836,250 Page 10 Art Unit: 1687 Application/Control Number: 17/836,250 Page 11 Art Unit: 1687
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