DETAILED ACTION
Comments
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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.
Claim 22 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12 September 2025.
Claims 1-10, 13-15, 17, 21-23, 25, 27, 31-33, 35-38, 40, and 43-45 are pending in the application.
Claims 1-10, 13-15, 17, 21, 23, 25, 27, 31-33, 35-38, 40, and 43-45 are examined in the instant Office action.
Withdrawn Rejections
The rejections under 35 U.S.C. 101 are withdrawn in view of argument on pages 13-15 of the Remarks. Specifically, the claims are subject matter eligible because the claims result in a practical application of a more computationally efficient algorithm for conducting a conventional algorithm with an analogous objective.
The double patenting rejection is withdrawn in view of amendments filed to the instant set of claims on 22 January 2026.
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.
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.
The following rejection is reiterated:
35 U.S.C. 103 Rejection #1:
Claim(s) 1-6, 8-10, 13-14, 21, 23, 25, 31-33, 35-37, and 43-45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gligorijevic et al. [bioRxiv, Machine Learning for Structural Workshop, NeurIPS, 2021; on IDS].
Claim 43 is drawn to a computer-implemented method. The method comprises identifying an input molecule exhibiting a value for one or more properties. The method comprises applying a molecule design computation model to generate an output molecules exhibiting a superior value for the one or more properties than the input molecule. The molecule design computation model generates the output molecule by at least encoding the input molecule to generate an embedding of the input molecule, and decoding the embedding of the input molecule to generate the output molecule. The method requires that the decoding the embedding of the input molecule generates the output molecule to exhibit a different molecular composition and/or a different molecular conformation than the input molecule. The method requires that the different molecular composition and/or different molecular conformation is associated with the superior value of the one or more properties.
Claim 44 is drawn to a computer-implemented method. The method comprises, for inclusion in a matched dataset, a plurality of molecule pairs. Each molecule pair of the plurality of molecule pairs includes two molecules exhibiting different values for one or more properties. The method comprises training, based at least on the matched dataset, a molecule design computation model to generate an output molecule having a superior value for the one or more properties than an input molecule. The method requires that the decoding the embedding of the input molecule generates the output molecule to exhibit a different molecular composition and/or a different molecular conformation than the input molecule. The method requires that the different molecular composition and/or different molecular conformation is associated with the superior value of the one or more properties. The method requires the training to include applying the molecule design computation model to generate, based at least on a first molecule in the molecule pair, a reconstruction of a second molecule in each molecule pair. The molecule design computation model is trained to generate the reconstruction if the second molecule. The method comprises encoding the first molecule to generate an embedding of the first molecule and decoding the embedding of the first molecule to generate the reconstruction of the second molecule. The method comprises applying the molecule design computation model to generate, based on the input molecule, the output molecule having a superior value for the one or more properties than the input molecule.
Claim 1 is drawn to similar subject matter as claim 43, except claim 1 is drawn to a system comprising processors.
Claims 5-6 and 31 are drawn to similar subject matter as claim 44, except claims 5-6 and 31 are drawn to systems comprising processors.
The document of Gligorijevic et al. studies function-guided protein design by deep manifold sampling [title]. Figure 1A of Gligorijevic et al. illustrates calmodulin, a protein with the property of binding calcium. Figure 1A of Gligorijevic et al. illustrates removing the calcium binding site of calmodulin, and applying a molecule design computation model by encoding the input molecule to generate an embedding of the input molecule and decoding the embedding of the input molecule to generate an output molecule.
Figure 1B of Gligorijevic et al. illustrates the pair cutinase and Sample 1, with the property of cutinase function. In Figure 1B, Gligorijevic et al. uses training, via applying a molecule computation model to the first molecule of the cutinase by encoding the first molecule to generate an embedding of the first molecule and decoding the embedding of the first molecule to generate the reconstruction of the second molecule (e.g. Samples 2-4). Figure 1B of Gligorijevic et al. teaches a reconstructed cutinase with superior functions relative to the initial cutinase. Each of Samples 2-4 have different values of seqid relative to Sample 1.
Gligorijevic et al. does not teach all of the computer limitations of the claims.
With regard to claims 2-4, 8-10, 13-14, 32-33, and 35-37, Figure 1B of Gligorijevic et al. applied the encoding and decoding the cutinase until the threshold of a 46.2 seqid is obtained. In Figure 1B of Gligorijevic et al. the seqid measurement is broadly interpreted to be either a proximity measure to the original cutinase or a difference in sequence from the original cutinase. In Figure 1B of Gligorijevic et al., Samples 1-4 illustrate a monotonicity of the seqid constraint. The higher the value of the seqid in Figure 1B of Gligorijevic et al. the closer the match is to the original cutinase. The properties of the cutinase are the seqid values and the biological properties of the cutinase.
With regard to claims 21 and 23, Figure 1 of Gligorijevic et al. uses the proteins/chemical compounds of calmodulin and cutinase.
With regard to claim 25, Figure 1B of Gligorijevic et al. illustrates a plurality of conformations of the output molecules.
With regard to claim 45, the seqid value of Figure 1B of Gligorijevic et al. measures structural similarity.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the protein design of Gligorijevic et al. by use of computers because it is obvious to automate a manual activity for improved accuracy and efficiency [In re Venner, 262 F.2d 91, 95, 120 USPQ 193, 194 (CCPA 1958), MPEP 2144.04 III].
Response to arguments:
Applicant's arguments filed 22 January 2026 have been fully considered but they are not persuasive.
Applicant argues that Gligorijevic et al. does not teach the amended limitations of the claims. Specifically, applicant argues that Gligorijevic et al. does not teach a resultant molecule that is superior to the initial molecule. This argument is not persuasive because Figure 1B of Gligorijevic et al. teaches a reconstructed cutinase with superior functions relative to the initial cutinase.
The following rejection is reiterated:
35 U.S.C. 103 Rejection #2:
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gligorijevic et al. as applied to claims 1-6, 8-10, 13-14, 21, 23, 25, 31-33, 35-37, and 43-45 above, in further view of Stanton et al. [Proceedings of the 39th International Conference on Machine Learning, volume 162, 2022, 20 pages; on IDS].
Claim 7 is further limiting wherein the training of the molecule design model includes reducing a reconstruction loss associated with a difference between the second molecule and the reconstruction of the second molecule generated by the molecule design computation model.
Gligorijevic et al. makes obvious applying computation models for protein design, as discussed above.
Gligorijevic et al. does not teach reconstruction loss.
The document of Stanton et al. studies accelerating Bayesian optimization for biological sequence design with denoising autoencoders [title]. Figure 2 of Stanton et al. teaches reconstruction of the biological sequence. Appendix B-1 of Stanton et al. teaches optimizing loss.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the protein design of Gligorijevic et al. by use of reducing of reconstruction loss of Stanton et al. wherein the motivation would have been that reducing loss results to optimal structures [abstract of Stanton et al.]. There would have been a reasonable expectation of success in combining Gligorijevic et al. and Stanton et al. because both studies analogously pertain to applying encoders to protein structure data.
Response to arguments:
Applicant has not arguments specific to Stanton et al.
The following rejection is reiterated:
35 U.S.C. 103 Rejection #3:
Claim(s) 17 and 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gligorijevic et al. as applied to claims 1-6, 8-10, 13-14, 21, 23, 25, 31-33, 35-37, and 43-45 above, in further view of Hie et al. [Nature Biotechnology, volume 42, 24 April 2023, 26 pages; on IDS].
Claims 17 and 40 are further limiting wherein the properties comprise binding affinity and immunogenicity.
Gligorijevic et al. makes obvious applying computation models for protein design, as discussed above. Figure 1 of Gligorijevic et al. teaches binding affinities.
Gligorijevic et al. does not teach immunogenicity.
The document of Hie et al. studies efficient evolution of human antibodies from general protein language models [title]. The abstract and figures of Hie et al. teach antibody immunogenicity.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the protein design using binding affinity of Gligorijevic et al. by use of the immunogenicity of Hie et al. wherein the motivation would have been that immunogenicity gives a physiological application to binding affinity [abstract of Hie et al.]. There would have been a reasonable expectation of success in combining Gligorijevic et al. and Hie et al. because both studies analogously pertain to applying machine learning to protein binding data.
Response to arguments:
Applicant has not arguments specific to Hie et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The following rejection is necessitated by amendment:
Claims [1 or 21], 2, and 43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 8, respectively, of U.S. Patent No. 12,131,801 B2 in view of Gligorijevic et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both studies are analogously applicable to optimizing protein design using encoding and decoding of data. However, the claims of ‘801 do not teach that the resultant protein is superior to the initial protein.
Figure 1B of Gligorijevic et al. illustrates the pair cutinase and Sample 1, with the property of cutinase function. In Figure 1B, Gligorijevic et al. uses training, via applying a molecule computation model to the first molecule of the cutinase by encoding the first molecule to generate an embedding of the first molecule and decoding the embedding of the first molecule to generate the reconstruction of the second molecule (e.g. Samples 2-4). Figure 1B of Gligorijevic et al. teaches a reconstructed cutinase with superior functions relative to the initial cutinase.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the protein design of the claims of ‘801 by use of the protein design of Gligorijevic et al. wherein the protein design of Gligorijevic et al. results is a protein with the biological application of having improved functions relative to the initial protein [Figure 1B of Gligorijevic et al.].
Response to arguments:
Applicant requests that this rejection be held in abeyance.
Allowable Subject Matter
Claims 15, 27, and 38 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 15, 27, and 38 are free of the prior art. With regard to claims 15 and 38, the prior art does not teach a multivariate rank indicative of a difference in a combination of the first property and the second property and determining that the criteria are satisfied based at least on a difference in a respective multivariate rank of the first molecule and the second molecule satisfying one or more thresholds. With regard to claim 27, the prior art does not teach the mathematical probabilities regarding properties of the multinomial distribution as applied to protein design.
Related Prior Art
The document of Gligorijevic et al. [WO 2022/245737 A1] teaches many limitations that overlap with the document of Gligorijevic et al. cited in the rejection statement regarding protein design and using encoders and decoders to further optimize the structure of proteins.
The document of Barot et al. [bioRxiv, 17 October 2022] studies automated protein function description for novel class discovery [title]. While Barot et al. also overlaps with the teachings of Gligorijevic et al., Barot et al. is directed more to protein classification and function description.
E-mail Communications 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 EFS-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
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the 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 Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062.
/RUSSELL S NEGIN/Primary Examiner, Art Unit 1686 11 February 2026