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. Information Disclosure Statement The IDS filed 9/15/2022, 2/22/2023, 10/25/2025, 12/18/2025 have been considered by the Examiner. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application 63/244262 filed 9/15/2021 is acknowledged. 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 1-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. Claims 1-12 and 15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Step 1: Process, Machine, Manufacture or Composition Claims 1-12 are drawn to a system comprising a processor, so a machine. Claims 13-14 are drawn to a system comprising a “peptide manipulator” to physically manipulate a polypeptide chain. The recited “peptide manipulator” does not include any physica l device structures and therefore reads on software per se with instructions for manipulating a physical polypeptide chain via a device . Also see the 112(a) and 112(b) rejections below. Claims 13-14 therefore encompass a computer program on computer readable media that sends instructions to devices . It is noted that a program, per se, is not a statutory category of invention, as set forth in In re Nuijten . As such, an embodiment of the claims read on non-statutory subject matter (In re Nuijten 84 USPQ2d 1495 (2007)). The applicants may overcome the rejection by 1) amendment of the claims to be limited to physical forms of computer readable storage media described in the specification or 2) by amending the claimed subject matter to be limited to “non-transitory”, see the notice regarding Computer Readable Media (1351 OG 212 (23 February 2010)). Claim 15 is drawn to a method, so a process. Step 2A Prong One: Identification of an Abstract Idea The claim(s) recite(s ) 1. apply at least one first movement restriction preventing rotation of at least one portion of a peptide backbone. This limitation reads on a mathematical concept. The process reads on performing molecular dynamics simulations wherein molecules are represented computationally through mathematical coordinates and forcefields. The application of a rotational restriction equates of applying a mathematical force equation on a theoretical object, e.g. as in a physics model which can be solved by the human mind and with math. The step is therefore an abstract idea . Hagler et al. (Journal of the American Chemical Society, vol. 98 (1976) pgs. 4600-4612) evidence that rotation or lack thereof in peptide molecular bonds can be modeled with mathematical force field potentials (Figures 7-8 and page 4602 section “Empirical Force Field Calculations , ” page 4605 section “Lattice Energy and Methyl Rotation,” page 4607 section “Methyl Rotation Barriers as Calculated from Potential Functions Derived from Crystal Data” ) 2. apply a first directional rotation to at least one second portion of the peptide backbone wherein the first directional rotation and movement restriction are applied simultaneously. This limitation reads on a mathematical concept. The process reads on performing molecular dynamics simulations wherein molecules are represented computationally through mathematical coordinates and forcefields. Applying a rotation of a mathematically modeled molecular bond equates to applying a mathematical torque function within the context of a molecular force field which is a mathematical equation. The step is therefore an abstract idea . 4. remove the applied first movement restriction and first directional rotation. This step reads on setting the applied restrictive and rotational forces to zero. T he step reds on math and is therefore an abstract idea . 5. apply a second movement restriction preventing rotation of a third portion of a peptide backbone and second directional rotation of a fourth portion of the peptide backbone, simultaneously . As set forth above, the application of rotational and restrictive force to portions of a mathematically represented molecule equates to applying rotational (i.e. torque) force and restrictive force by modeling torsion potentials and mechanical force fields which are mathematical equations. The application of equations representing force, restrictive and rotational, to a mathematically represented object is an abstract idea . Claims 2-4, 7-12 and 15 are drawn to steps further detailing the molecular force modeling and are therefore also abstract ideas. Step 2A Prong Two : Consideration of Practical Application The claims do not recite additional elements that integrate the abstract idea into a practical application . The claims are drawn to mathematical modeling of molecular forces which is an abstract idea. This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria: An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field; an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition; an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim; an additional element effects a transformation or reduction of a particular article to a different state or thing ; and an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. Step 2B : Consideration of Additional Elements and Significantly More The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to: 1. wherein applying directional rotations and movement restrictions are performed in vitro . This limitation is tangentially recited and reads on the folding of peptides in an in vitro environment wherein natural rotational and restrictive forces are exerted on a peptide. Also see the 112(b) rejection below. 2. wherein applying the directional rotations and movement restrictions are performed in silico as part of a computer simulation. This limitation is tangentially recited as the technical environment in which the abstract idea is performed. Molecular dynamics simulations are routinely performed with a computer that constitutes an in silico environment. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because placing peptides in to an in vitro environment where viscosity and temperature will a ffect the folding of peptides by restricting portions from moving while other portions rotate is routine, conventional and well understood. Other elements of the method include the recitation of an in silico environment (claim 6) and processor (claim 1) which is a recitation of generic computer structure that serves to perform generic computer functions that are well-understood, routine, and conventional activities previously known to the pertinent industry. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter. Claim Rejections - 35 USC § 112-1 st paragraph The following is a quotation of the first paragraph of 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 13-14 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. Considerations under 112(f) : Claim s 13-14 are drawn a system comprising a “peptide manipulator” which is configured to physically manipulate a polypeptide chain by applying a movement restriction to a portion of the backbone and a directional rotation or other movement to a second portion of the back bone, remove the applied restriction and rotation, and apply said restriction and rotation to a third and fourth portion of the backbone, respectively. The claims recite means plus function language wherein the “means” is the “peptide manipulator.” A review of the specification does not show written description for a peptide manipulator configured to perform the recited functions of applying a restriction and rotation to portions of a peptide back bone, remove these applied forces and apply them to different portions of a peptide backbone. The specification discloses that these process can be performed by: [0049] Output control interface 206 is operable to output control signals to physical peptide manipulation components. In one aspect, the control signals are provided to components configured for performing in vitro peptide manipulation. Exemplary components include, but are not limited to one or more robotic arms and end effectors, components such as various solid phases for covalent, non-covalent and/or affinity protein immobilization, molecular tweezers, lasers, optical tweezers, magnetic tweezers, magnetic beads, electromagnets, piezoelectric devices, piezoacoustic devices, nanodevices, microfluidic devices, electromagnetic field generators, and the like. [0053] In one aspect, movement restriction(s) is/are applied via at least one of an established force field, electrical force(s), magnetic force(s), mechanical force(s), covalent and/or non-covalent binding forces or characteristics, and other force(s). In one aspect, applying at least one first movement restriction may comprise applying at least one force to an amino acid, where the at least one force is of sufficient magnitude to restrict movement of at least one of the amino acid and portions of the peptide backbone in proximity to the amino acid. In one aspect, applying at least one first movement restriction may comprise applying at least one force to a plurality of amino acids, where the at least one force is of sufficient magnitude to restrict movement of at least the plurality of amino acid and portions of the peptide backbone in proximity to the plurality of amino acids. In one aspect, the movement restriction(s) are applied to at least one of an N-terminal amino acid, a C-terminal amino acid, and any other amino acid of the peptide backbone. In one aspect, applying movement restriction(s) comprises modifying at least one of a temperature, a chemical composition, and a viscosity of a solvent in which the peptide is located. [0059] I n one aspect, the movement restriction(s) and directional rotation(s) are applied in vitro. In one aspect, in vitro application of movement restriction(s) and directional rotation(s) are performed using at least one of optical tweezers, magnetic tweezers, magnetic beads, electromagnets, piezoelectric devices, and piezoacoustic devices. In one aspect, the process is used to produce at least one artificial protein having at least one of a native and a non-native folding conformation . However, the specification does not describe a system for performing the claimed targeted and selected application of restriction and rotational forces as claimed. In order to apply a rotational and restriction force, remove the forces and reapply them to different parts of a peptide backbone, one of ordinary skill would need to isolate and manipulate specific atomic bonds in a molecule and apply targeted force . The specification does not provide written description for a system that can restrict physical bonds in a physical peptide molecule and also impose an artificial rotation on a physical bond in a physical peptide molecule while also preventing another portion of the molecule from rotating . A general description of means are disclosed, i.e. optical tweezers, magnetic tweezers, magnetic beads, electromagnets, piezoelectric devices, and piezoacoustic devices , is insufficient structure to perform the claimed functions of applying a restrictive force to prevent rotation of a portion of a peptide backbone while simultaneously applying a rotation to a second portion of the backbone, remove these forces and then reapply them to two other portions of the backbone. Optical tweezers can trap and rotate particles. Magnetic beads, electromagnets, piezoelectric devices, and piezoacoustic devices can similarly trap and measure forces of molecules. However, a written description means for simultaneously restricting and rotating bonds of a peptide backbone are not disclosed. Claim Rejections - 35 USC § 112-2 nd paragraph The following is a quotation of the second paragraph of 35 U.S.C. 112: 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 1-15 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claims 1, 13 and 15, fourth step, recite applying a second movement restriction to a third portion of “a peptide backbone,” In the following, fifth step, the claims recite applying a second rotation to a fourth portion of “ the peptide backbone .” It is unclear if these second restriction and rotation are applied to the same peptide backbone as the first movement restriction and rotation. If not, it is unclear if the antecedent basis provided by “ the peptide backbone ” in the fifth step is referring the peptide with the first forces applied or another peptide with the second forces applied. If applicants intend the first, second, third and fo urth portions of the backbone to be on the same peptide, it is suggested that the fourth step of the claims be amended to recite applying a second movement restriction to a third portion of “[a] the peptide backbone.” This would make clear that only one peptide is being manipulated by the applied forces and removal thereof. Claim 6 recites wherein applying directional rotations and movement restrictions are performed in vitro. The instant specification discloses: [00 48] .. control signals are provided to components configured for performing in vitro peptide manipulation. Exemplary components include, but are not limited to one or more robotic arms and end effectors, components such as various solid phases for covalent, non-covalent and/or affinity protein immobilization, molecular tweezers, lasers, optical tweezers, magnetic tweezers, magnetic beads, electromagnets, piezoelectric devices, piezoacoustic devices, nanodevices, microfluidic devices, electromagnetic field generators, and the like. However, claim 1 from which claim 6 depends is drawn to a processor and memory with instructions for applying a movement restriction and rotation simultaneously to the peptide backbone, removing the restriction and rotation and applying the restriction and rotation to other portions of the backbone. The components disclosed in par. 0048 of the specification are insufficient and alone incapable of a simultaneous application of a restrictive and rotational force to portions of a peptide and targeted removal of the forces for reapplication of the forces to other portions of the backbone. Therefore it is unclear how claim 6 is intended to further limit the computation process of claim 1. Claim 1 is interpreted as a computerized molecular mechanics simulation (i.e. molecular dynamics). For the purpose of examination, claim 6 is interpreted as placing peptides into an in vitro environment where peptide motion and folding takes place. Considerations under 112(f): Claims 13-14 are drawn a system comprising a “peptide manipulator” which is configured to physically manipulate a polypeptide chain by applying a movement restriction to a portion of the backbone and a directional rotation or other movement to a second portion of the back bone, remove the applied restriction and rotation, and apply said restriction and rotation to a third and fourth portion of the backbone, respectively. The claims recite means plus function language wherein the “means for” is the “peptide manipulator.” It is unclear what the structure of the “peptide manipulator” is intended to be such that it can perform the claimed functions. The metes and bounds of the “peptide manipulator” are therefore unclear. As set forth under 35 USC 112(a), t he specification does not provide a description for the structure of the “means ” (i.e. the peptide manipular) for carrying the claimed steps. One would not know what is needed to be a “peptide manipulator” for simultaneously restricting and also rotating separate portions of a peptide backbone. It is therefore unclear what structure corresponds to the “peptide manipulator” and o ne would not know what is needed to be a means for carrying out the claimed steps. Applicant is required to: (a) Amend the claim so that the claim limitation will no longer be a means (or step) plus function limitation under 35 U.S.C. 112, sixth paragraph; or (b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the claimed function without introducing any new matter (35 U.S.C. 132(a)). If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant is required to clarify the record by either: (a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or (b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made. This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a). Claim s 1-12 and 15 are rejected under 35 U.S.C. 103(a) as being unpatentable over Sahakyan et al. ( "Energy-dependent protein folding: modeling how a protein folding machine may work," September 18, 2020, pgs. 1-24 [retrieved from the internet 3/16/2026] <URL: https://doi.org/10.1101/2020.09.01.277582> ) Sahakyan et al. teach (Abstract) protein folding with molecular dynamics simulations that were augmented by the application of mechanical force to rotate the C terminal amino acid (i.e. first directional rotation) while simultaneously limiting the N-terminal amino acid movements ; the peptide backbone, is mechanically manipulated we in molecular dynamics simulations augmented by application of torsion to the peptide backbones where the C-termini of various polypeptides are mechanically rotated either clockwise or counterclockwise, while the motions of their N-termini were restricted (page 3, par. 5) (i.e. apply at least one first movement restriction preventing rotation of a first portion of a peptide backbone), as in claim s 1 and 15 . Sahakyan et al. teach (Abstract and page 3, par. 5 ) simultaneously applying mechanical force to rotate the C terminal amino acid (i.e. apply first directional rotation to second portion of peptide backbone, wherein first and second movement restrictions are applied simultaneously), as in claim s 1 and 15 . Sahakyan et al. teach (page 11, Table 2) four different variations of simulations including adding restraints and rotations and having no restrains or rotations (Table 2, first column)(i.e. remove the restraints and rotation)(i.e. remove the applied first movement restriction and first directional rotation), as in claim s 1 and 15 . Sahakyan et al. teach (page 11, Table 2) five different peptides where four different variations of simulations including adding restraints and rotations and having no restrains or rotations are applied, wherein any one of the additional four peptides would read on a third and fourth portion of a peptide backbone (i.e. apply at least one second movement restriction preventing rotation or a third portion of backbone and apply at least one directional rotation to at le a st one fourth portion of the peptide backbone), as in claim s 1 and 15 . In an alternative embodiment claim 1 can be interpreted as removing the restraint and rotation from the backbone of the peptide and re-introducing the restraint and rotation to a third and fo u rth portion of the same peptide. Sahakyan et al. teach one pair of portions with a restraint and rotation but do not teach moving the restraint and rotation to a third and fourth portion, respectively, on the same peptide. However, Sahakyan et al. make this obvious by teaching that the restraint and rotation are added to four bonds on each of the C-terminal and N-terminal of the peptide (page 13, Figure 1); Sahakyan et al. teach selecting positions along the backbone to add the restraint and rotation (page 6, par. 3-5) by changing the force in the force field (page 6, par. 3-5) . It would have been obvious to one of ordinary skill in the art at the time the invention was made to have selectively applied rotational force and a restrictive force to any selected bonds on a peptide backbone with molecular force fields as taught by Sahakyan et al. Sahakyan et al. teach that the forces are applied by selection to positions along a peptide back bone (page 6, par. 3-5), by changing the force in the force field (page 6, par. 3-5) used to calculate molecular bond rotations. Sahakyan et al. teach that one of ordinary skill would know how to manipulate a molecular forcefield to selectively apply rotational forces and force constraints. Adjusting force constraints and rotational forces on a peptide backbone is merely an application of known techniques according to known elements taught by Sahakyan et al. Regarding dependent claims 2-12 Sahakyan et al. teach (page 4, par. 3) that the restraint and rotational force influence the folding of the peptide so that some peptides fold similar to their native structures (i.e. restriction and rotation cause some twisting of the peptide backbone and change to conformation of the polypeptide change), as in claim 2. Sahakyan et al. teach (page 4,par. 1) applying a restriction force and toque at a first and second location of the backbone, as in claims 3-4. Sahakyan et al. teach molecular dynamics simulations (Abstract) which suggests in silico simulations, as in claim 5. Sahakyan et al. teach (page 3, par. 2) that the process mimics what occurs in vitro which would make it obvious for one of ordinary skill to allow the simulated peptides to fold in vitro, as in claim 6. Sahakyan et al. teach (page 3, par. 5) molecular dynamics simulations are augmented by application of torsion to the peptide backbones ; the C-termini of various polypeptides were mechanically rotated either clockwise or counterclockwise, while the motions of their N-termini were restricted. Sahakyan et al. teach adding the restraints and rotational force with the GROMACS force field (page 6-7, connecting par. ), as in claims 7-10. Sahakyan et al. teach (Figure 1) that the peptide is modeled with covalent bonds, as in claim 11. Sahakyan et al. teach (page 6, par. 3) using and NVT ensemble and then keeping temperature constant after equilibration (i.e. modifying temperature), as in claim 12. E-mail communication Authorization Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EF S Web (using PTO/SB/439) or Central Fax (571-273-8300): Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file. Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03 . Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-7035. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Anna Skibinsky/ Primary Examiner, AU 1635