DETAILED ACTION
Applicant's response, filed 10/27/2025, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/27/2025 has been entered.
Status of the Claims
Claims 1 and 6-7 are examined; claims 2-5 are canceled.
Priority
This application is a 371 of PCT/KR2018/012335 (10/18/2018) and claims priority from Foreign Application No. 10-2018-0124342 (10/18/2018) as reflected in the filing receipt mailed on 10/19/2021. The claims to the benefit of priority are acknowledged and the effective filing date of claims 1 and 6-7 is 10/18/2018.
Withdrawal / Revision of Objections and/or Rejections
In view of the amendment and remarks from 10/27/2025, the rejection of claims 1 and 6 under 35 U.S.C. § 101 is hereby withdrawn in view of Applicant's amendments, rendering the ground of rejection moot. The examiner recognizes that the claims directed to “selecting from the visual representation of the predicted absorbance change, the amino acid having the desired absorbance; and synthesizing the amino acid sequence having the desired absorbance utilizing the amino acid having the desired absorbance selected” provides evidence of additional elements (i.e. synthesizing step) altered based on the predicted results. Furthermore, “selecting from the visual representation of the predicted absorbance change, the amino acid having the desired absorbance; and synthesizing the amino acid sequence having the desired absorbance utilizing the amino acid having the desired absorbance selected” integrates the judicial exception into a practical application and could improve the operation of “predicting an absorbance change arising from adsorption of the target molecule onto an amino acid to form a complex” at Step 2A, Prong 2. The following rejections and/or objections are either maintained or newly applied for claims 1 and 6.
Claim Interpretation
Claim 1 recites “absorbance” which is interpreted as the intensity of a transition between energy levels in a molecule.
Claim 1 recites “interaction force” which is interpreted as being inherently present when a change in charge distribution occurs.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of pre-AIA 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, 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 negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 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 pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Fitch L. et. al. (Fitch L. et. al. “Prediction of Ultraviolet Spectral Absorbance Using Quantitative Structure-Property Relationships” J. Chem. Inf. Comput. Sci. 42(4):830-840 (2002) – referred to in the action as Fitch) in view of Siddarth P. et. al. (Siddarth P. et. al. “Electron-Transfer Reactions in Proteins: An Artificial Intelligence Approach to Electronic Coupling” J. Phys. Chem. 97(10):2400–2405 (1993) – referred to in the action as Siddarth) in view of Prasad et. al. “Near UV-Visible electronic absorption originating from charged amino acids in a monomeric protein” Chem. Sci. 8:5416–5433 (2017) – referred to in the action as Prasad – in view of Majidi et. al. “Aromatic amino acids adsorption on graphyne: a density functional theory study” Struct Chem 26:5-10( 2015) – referred to in the action as Majidi.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Independent claim 1 recites “obtaining the desired absorbance wherein predicting the absorbance change and obtaining the desired absorbance comprises: S1) predicting a structure having lowest energy of an amino acid and a target material comprising: (S1a) calculating lowest energy and frequency of the amino acid and the target material; (S1b) identifying if the amino acid and the target material are in lowest energy and positive frequency; and repeating step (S1a) until the amino acid and the target material are in lowest energy and positive frequency in step (S1b); (S2) analyzing an interaction force between the amino acid and the target material comprising: (S2a) forming the complex compound by analysis of the interaction force between the amino acid and the target material; (S2b) calculating lowest energy and frequency of the complex compound of the amino acid and the target material by DFT; and (S2c) identifying if the amino acid and the target material are in lowest energy and positive frequency; and repeating steps (S2a) and (S2b) until the amino acid and the target material are in lowest energy or positive frequency in step (S2c)” and “(S4) predicting an absorbance change using the S1 states calculated in the step S3 comprising calculating a change in the S1 state of the target material by the interaction force between the amino acid and the target material, or a change in the S1 state of the amino acid by the interaction force between the amino acid molecule and the target material molecule”. Fitch teaches a computational model (i.e. computer-implemented method) for predicting the relative response (pg. 830 para. 1) and spectral absorbance (pg. 830 title) of organic molecules for use in spectrophotometric detection of reaction products in organic chemistry (i.e. reads intermolecular interactions involving organic molecules such as amino acids) (pg. 830 para. 1) involving structural descriptors from fully energy-minimized structures (i.e. reading on “calculating lowest energy states” and on “repeating steps until structures are in the lowest energy” since structures are being “fully” energy minimized) (pg.834 col. 2 para. 2); wherein the energy absorbed by a molecule cause electrons to change energy states (i.e. reading on “predicting absorbance” - intensity of a transition between energy levels in a molecule) (pg. 834 col. 1 para. 1); and the transition frequency can be predicted by calculating the energies of excited electronic states (i.e. “positive frequency”) by a configuration interaction calculation with the intensity of the transitions or oscillator strength obtained from the transition dipole moment being proportional to the change in the electric charge distribution (i.e., reading on “analyzing the interaction force” and “calculating a change in the S1 state of the amino acid by the interaction force” – being interaction force the cause for the change in the electric charge distribution) occurring during excitation (pg. 831 col. 2 para. 8); wherein the computational model is performed throughout iterations until a stop event occurs (i.e. reading on repeating the steps described above for (S1a) (S1b) (S2a) (S2b)) (pg. 833 col. 2 para. 5) reading on the recited limitations in claim 1.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Regarding claim 1, Fitch does not explicitly teach “S3) calculating S1 state of each of the amino acid and the target material and S1 state of a complex compound of the amino acid and the target material comprising: (S3a) calculating the S1 state of each of the amino acid and the target material and the S1 state of the complex compound of the amino acid and the target material by DFT; (S3b) analyzing molecular orbital (MO) for the S1 state of each of the amino acid and the target material and the S1 state of the complex compound; (S3c) identifying if the S1 state of each of the amino acid and the target material and the S1 state of the complex compound is a valence excitation”. However, Siddarth teaches long-range electron-transfer reactions between amino acid residues in proteins (i.e., a complex compound comprising a number of amino acids) with electronic interactions treated using artificial intelligence and quantum mechanical formulation of superexchange (i.e. which comprises density functional theory framework) (pg. 2400 col. 2 para. 1); involving calculations of the energy difference from the transition state of the electron-transfer reaction to the products of the charge-transfer excitation process; and of the absorption maximum associated with this charge transfer (i.e. calculating S1 state) (pg. 2404 col. 2 para. 3). Siddarth teaches the estimation of the donor acceptor orbital energy at the transition state (i.e., reading on analyzing molecular orbital) (pg. 2404 col. 1 para. 5); wherein quantum mechanical method which makes use of all the valence orbitals (i.e. valence excitation) of the selected amino acid residues to calculate values of electronic coupling (pg. 2404 col. 1 para. 2) and wherein the overlap between atomic orbitals takes into account the effect of mutual orientations of amino acids for charge transfer calculations (i.e. reading on excitation that is not the valence excitation) (pg. 2401); reading on the recited limitation in claim 1.
Regarding claim 1, Fitch does not explicitly teach “method for synthesizing an amino acid sequence having a desired absorbance” and “(S3d) displaying a visual representation of molecular orbital (MO) for the S1 state of each of the amino acid and the target material and the S1 state of the complex compound determined in step (S3b) on a display of a computer; wherein when it is not the valence excitation in the step S3c, it is a charge transfer excitation, and when it is the valence excitation in the step S3c, the valence excitation is the valence excitation in the target material or the valence excitation in the amino acid” and “(S5) displaying a visual representation of the predicted absorbance change calculated in step S4 on the display of the computer; wherein the amino acid is at least one selected from the group consisting of arginine (R), histidine (H), lysine (K), aspartic acid (D), glutamic acid (E), serine (S), threonine (T), asparagine (N), glutamine (Q), cysteine (C), selenocysteine (U), glycine (G), proline (P), alanine (A), valine (V), isoleucine (I), leucine (L), methionine (M), phenylalanine (F), tyrosine (Y) or tryptophan (W) and b) selecting from the visual representation of the predicted absorbance change, the amino acid having the desired absorbance; and synthesizing the amino acid sequence having the desired absorbance utilizing the amino acid having the desired absorbance selected in b)”. However, Prasad teaches a visual representation of molecular orbital (MO) for the S1 state in the form of a simulated absorption spectra (wavelength vs. oscillator strength) (i.e. predicted absorbance change) for Gly (control) and Lys (K) and Glu (D) monomers wherein the assignment of transitions in the spectra to charge transfer vs. non-charge transfer transitions across the absorption profile can be visualized (i.e. comprising “wherein when it is not the valence excitation in the step S3c, it is a charge transfer excitation”) along with the average ground state HOMO–LUMO gap (i.e. comprising valence excitation) (pg. 5423 Fig. 4); systematic experimental and theoretical investigations to test the UV-Vis absorption spectrum of a small monomeric, synthetic α3C protein (pg. 5418 col. 1 para. 2); wherein peptides were synthesized by solid phase peptide synthesis (pg. 5418 col. 2 para. 4); wherein the comparison of absorption spectrum of the intact a3C protein with that of a solution mixture of constituent amino acids in α3C was reported (pg. 5421 Fig. 2) (i.e. reading on synthesis of amino acids for which the absorbance was predicted); reading on the recited limitation in claim 1.
Regarding claim 1, Fitch does not explicitly teach “predicting an absorbance change arising from adsorption of the target molecule onto an amino acid to form a complex” or “using first-principles based on density functional theory (DFT)”. Regarding claim 6, Fitch does not explicitly teach “wherein the target material is selected from the group consisting of benzene, toluene, xylene, aniline, and toluidine”. Regarding claim 7, receiving the desired absorbance arising from adsorption of the target molecule onto the amino acid to form the complex prior to step”. However, Majidi teaches the interaction/adsorption of aromatic amino acids on geometry structures of supercell of ᵞ-graphyne (i.e. comprises benzene in its formulation) (pg. 6 Fig. 1); wherein optical and electronic properties can be investigated (i.e. reading on predicting an absorbance change arising from adsorption of the target molecule onto an amino acid to form a complex since absorbance is an optical property) (pg. 5 col. 2 para. 2); wherein the energy band gap of c-graphyne is decreased by the amino acids adsorption (i.e. band gap decrease comprises energy absorbance) (pg. 5 col. 1 para. 1); wherein the computational model details involved DFT calculations (i.e. reading on the receiving step) and the geometry of the complexes being minimized up to 0.01 eV/A° (i.e. lowest energy of an amino acid and a target material); reading on the recited limitation in claims 1 and 6-7.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 1 and 6-7, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings by Siddarth, Prasad and Majidi to a computational model for predicting the relative response of organic molecules by Fitch to predict absorbance change based on the calculated lowest energy state, positive frequency and the interaction force between of a complex compound of the amino acid and the target material using first-principles based on density functional theory; and to analyze/visualize molecular orbitals of the lowest energy states including charge transfer excitation and valence excitation states. One of ordinary skill in the art would be motivated to apply the teachings by Siddarth, Prasad and Majidi to the method by Fitch to explore how the protein structure (i.e. complex compound involving amino acids) controls the electronic coupling in electron-transfer (i.e., charge/energy transfer) reactions (pg. 2400 para 1 Siddarth); to monitor structure and dynamics of proteins (pg. 5431 col. 2 para. 1 Prasad); and to develop biosensor based on interaction s with amino acids (pg. 10 col. 1 para. 1 Majidi). One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to the use of computational methods to analyze the intensity of energy transition involving organic molecules interactions.
Response to applicant's remarks in regards of Claim Rejection 35 U.S.C. ~ 103
The Remarks of 10/27/2025 have been fully considered but are not persuasive for the reasons below:
Applicant asserts “The references, taken alone or in any fair combination do not teach or suggest a method of synthesizing an amino acid sequence having a desired absorbance. Accordingly, amended claim 1 is nonobvious and allowable over Fitch, Siddarth, Prasad, and Majidi. By virtue of its dependency from claim 1, which is allowable, claim 6 is also allowable over Fitch, Siddarth, Prasad, and Majidi. Accordingly, Applicant respectfully requests that the rejection based on Fitch, Siddarth, Prasad, and Majidi be withdrawn” – pg. 6 para. 1-3. "One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references" (MPEP 2145 § IV). This argument is unpersuasive, because it analyzes the teachings of the references separately and independently, whereas the rejection is based on the combined teachings of the references. While none of the references teach all claim limitations, and the examiner does not dispute Appellant's identification of material missing from each one, all the claim limitations are taught by the combination of references, as explained previously. The fair combination of teachings over the prior art has been established. The examiner clarifies that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Accordingly, the combination of teachings by Fitch, Siddarth, Prasad and Majidi would allow a person of ordinary skill in the art to possess the claimed invention at the time of the effective filing date of the present application because one would be motivated to explore how the protein structure (i.e. complex compound involving amino acids) controls the electronic coupling in electron-transfer (i.e., charge/energy transfer) reactions (pg. 2400 para 1 Siddarth); to monitor structure and dynamics of proteins (pg. 5431 col. 2 para. 1 Prasad); and to develop biosensor based on interactions with amino acids (pg. 10 col. 1 para. 1 Majidi). Furthermore, in this instant application, the amendments support existing claim rejections, in which the recited limitations are all addressed, see Claim Rejections above.
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 THREE-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 final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCINI A FONSECA LOPEZ whose telephone number is (571)270-0899. The examiner can normally be reached Monday - Friday 8AM - 5PM ET.
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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685