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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02 March 2026 has been entered.
Status of the Claims
Claims 1-4 are pending and examined herein.
Claims 5-11 are withdrawn following an election made without traverse in the reply filed on 20 December 2023.
Claims 12-23 are canceled.
Priority
As detailed on the 24 April 2020 filing receipt, the application claims priority as early as 17 October 2017. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
Information disclosure statements (IDS) were submitted on 05 December 2025 and 02 March 20265. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Withdrawal / Revision of Objections and/or Rejections
The rejection under 35 USC 103 was previously withdrawn. Similar art, such as Umeyama (US 2010/0312538 A1; previously cited), Yamazaki (Journal of Physical Chemistry B 115(2): 310-318, 2011; previously cited on the 03 September 2024 PTO-892 form), and Rajgaria (Proteins 70(3): 950-970, 2008; previously cited on the 10 June 2025 PTO-892 form), do not teach the required aspects of the geometric averaging based on the distribution function for each atom., and thus the claims are considered free of the prior art.
The claim objection is withdrawn as the previous language was amended/removed.
The following objections and/or rejections constitute the complete set of objection and/or rejections for the instant application. Objections and/or rejections that follow are either maintained or newly applied.
Claim Interpretation
In the specification, a "probe" is interpreted to refer to an amino acid, a "target structure" is interpreted to refer to a compound, and a "plurality of unit structures" is interpreted to refer to a plurality of atoms (pg. 3, paragraph [10]). In a broadest reasonable interpretation, these are interpreted as in silico representations of the molecules.
The term "feature quantity" is not defined. It occurs in the specification as "a descriptor (feature quantity)" (pg. 2, paragraph [5]), and a "fingerprint" is used as an example. Therefore, this term will be interpreted as any kind of quantitative feature of the molecule representation.
Claim 1 recites an external database where screening occurs. The database is not recited as part of the computer and is present in a wherein clause, and therefore is considered to be an intended use of the feature quantity and not required by the claims.
Claim Objections
Claim 1 is objected to because of the following informalities: the “performing” step is followed by a list of substeps, and thus should likely read “... recorded in the external database:[[;]]” with a colon rather than semicolon, and elements (C) and (D) should be joined by a conjunction “and.” Furthermore, the claim recites “designating compound” and should likely read “designating a compound”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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 1-4 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The terms “degree of matching” and “high likelihood” in claim 1 are relative terms which render the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Additionally, the “degree” metric is unclear by which the matching is judged. Because it is unclear what a high degree of likelihood is based on the matching degree is, it is unclear which compounds will be extracted. Claims 2-4 are dependent on claim 1 and do not remedy this lack of clarity and so are rejected on similar grounds.
Claim 1 also recites “an evaluation value calculating step” within both the element (C) of the performing step and on its own after the “performing” step, rending the term unclear. Because the evaluation value calculating step within the “performing” step is for determining the first value and the other evaluation value calculating step is to determine the second value, amendment to recite “a first evaluation value calculating step” and “a second evaluation value calculating step” or a similar amendment may overcome the rejection. Claims 2-4 are rejected on similar grounds.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 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 1-4 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “calculating a second value of a ligand that is a compound whose binding to the target has been confirmed,” “calculating a degree of matching” between values, and “extracting one or more compounds having a high likelihood of binding to the target protein based on the calculated degree of matching.” The support in the disclosure for the second value, while not explicitly called as such, is the calculation of a confirmed ligand’s value (specification: paragraph [56]). It is further disclosed similarity is calculated between the target compound value (i.e., the first value) and the known ligand value (i.e., the second value). The metric of similarity is disclosed as comparison to a threshold (paragraph [60]). The recited “degree of matching” is not recited in the specification and a threshold is not recited in the claims. The recited “high likelihood” implies a mathematical concept that is not claimed nor disclosed. Therefore, the claim is considered to introduce new matter. Claims 2-4 are dependent on claim 1 and rejected on similar grounds. This rejection may be overcome by amendment to recite the comparison to a threshold as disclosed in the specification as a metric for determining which compounds to extract, or a similar amendment may be entered.
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 1-4 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of "feature quantity calculating."
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prone One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of
Matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is
the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a method (claims 1-4), which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
The claims recite designating a compound as the target, where designating is interpreted as a data selection and thus performable by the human mind and is a mental process.
The claims recite calculating a first evaluation value reflecting intermolecular interaction properties contributing to binding the target protein by quantifying degree of accumulation of probes by the generated three dimensional structure, where calculations of values based on the structure is interpreted on a mental step of determining numerical values based on observe properties then a mathematical step of calculating a total evaluation value. Calculating the second evaluation value similarly rejected.
The claims recite calculating a degree of matching between the first and second evaluation values. This step is interpreted as a comparison of numerical values and thus may be performed mentally, as the human mind is practically equipped to perform a comparison of two values, or as a mathematical concept such as determining a difference.
Claim 1 recites extracting compounds. The compounds are data in memory, and their extraction is interpreted as their selection. Data is abstract, and selection is a step the human mind is practically equipped to perform.
Claim 1 further recites "the distribution function… is obtained by geometrically averaging the distribution function… for each atom" and calculating the evaluation value in mathematical and verbal terms. A mathematical relationship may be expressed in words and there is no particular word or set of words that indicates a claim recites a mathematical calculation (MPEP 2106.04(a)(2)).
Dependent claim 2 recites "quantifying… a degree of accumulation," where quantification is interpreted as arithmetic and therefore an abstract idea. Dependent claim 3 recites a step "converting the first feature into an invariant," which is interpreted as a mathematical concept. Dependent claim 4 recites a calculating step and therefore is interpreted as a mathematical concept.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Claim 1 recites “a computer,” “an external database,” “a network,” "one or more central processing units “storing, in a storage,” and "generating a three-dimensional structure."
The computer, database, processors, and network are interpreted as general purpose computer elements. The claims do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Claim 1 also recites "generating a three-dimensional structure" which is performed in preparation of the mathematical steps and is interpreted as insignificant extra solution activity (MPEP 2106.05(g)), which is required to perform the evaluation value calculation step.
The recited storing data in storage is for collecting information prior to an extracting step, and thus is interpreted as insignificant extra solution activity (MPEP 2106.05(g)).
The dependent claims do not recite any elements in addition to the abstract ideas. Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are directed to that abstract idea. Claims that are directed to abstract ideas must be examined further to determine whether the additional elements besides the abstract idea render the claims significantly more than the abstract idea. Claims that are directed to abstract ideas and that raise a concern of preemption of those abstract ideas must be examined to determine what elements, if any, they recite besides the abstract idea, and whether these additional elements constitute inventive concepts that are sufficient to render the claims significantly more than the abstract idea (MPEP 2106.05). [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Claim 1 recites “a computer,” “an external database,” “a network,” "one or more central processing units “storing, in a storage,” and "generating a three-dimensional structure." Claim 2 also recites data storage.
As explained above, the recited computer amounts to using a computer as a tool to perform an abstract idea (MPEP 2106.05(f)). The recited "storing" step, which is interpreted as requiring a computer, is further interpreted as storing and retrieving information in memory (Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93) and therefore well-understood, routine, and conventional (MPEP 2106.05(d)(II)(iv)). The step of performing the data screening over a network is also interpreted as a conventional computer task (buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014)).
Claim 1 additionally claims generating a three-dimensional structure formed by a plurality of units. Cozzini (Current Medicinal Chemistry 11: 3093-3118, 2004; previously cited on the 10 June 2025 PTO-892 form) teaches a review of computing free energy associated with macromolecules based on force fields (abstract) and the importance of obtaining a three-dimensional structure to determine binding to active sites (pg. 3093, col. 2, paragraph 1) and comparison to a reference in a database (pg. 3104, col. 1, last paragraph).
Therefore, none of the claims recite additional elements which would clearly amount to significantly more. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Response to the 02 March October 2026 Applicant Remarks
Applicant remarks assert the steps of "generating the three-dimensional structure," "calculating evaluation values," "storing," and "extracting" are not mere data manipulations because the evaluation values are computed based on physical properties of molecular structures, including chemical interaction information such as van der Waals forces and the center of mass and the evaluation is performed using ligands known to bind the target protein, thereby incorporating real physical constraints governing molecular binding (pg. 7, last paragraph to pg. 8., first paragraph). This assertion is interpreted as directed to Step 2A Prong One of 101 analysis, which is used to determine whether the claim recite an abstract idea (MPEP 2106.04(a-c)). It is agreed at least some of the recited concepts are not abstract, particularly generating the three-dimensional structure and storing information, which is reflected in the rejection above where they are treated as elements in addition to the abstract ideas at Steps 2A Prong Two and 2B. The steps calculating evaluation values are asserted to be based on physical properties of molecular structures and incorporate real constraints. However, the compounds are data, and data is generated from the structure, and analysis of the data to generated numbers for comparison is a mathematical concept. The math being based on physical constraints does not prevent them from being math. Furthermore, the physical constraints are generated from a simulated structure and thus are also data and not physical measurements of a real structure. Finally, the extracting step is interpreted as selected data stored in storage. However, even if it was interpreted as interaction with storage, such a step is still a conventional computing task of receiving and retrieving data in memory (Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93), which does not provide significantly more than the abstract ideas (MPEP 2106.05(d)(II)).
Applicant remarks assert the method enables more accurate identification, from a database, of compounds that are highly likely to bind to the target protein and possess the desired properties, which improves structure-based compound screening technology by enhancing the precision and reliability of molecular evaluation, representing a technical improvement over conventional methods (pg. 8, first paragraph). Identification of compounds is based on the abstract steps of calculating evaluation values and comparison to a threshold metric or significance value. The claims culminate in data in the form of retrieval or selection of a structure stored in memory. That is, they begin and end with data. The non-abstract steps are not recited in a way that is an improvement to the state of the art nor unconventional, at least in view of Cozzini, where computing free energy associated with macromolecules based on force fields (abstract) and the importance of obtaining a three-dimensional structure to determine binding to active sites (pg. 3093, col. 2, paragraph 1) and comparison to a reference in a database (pg. 3104, col. 1, last paragraph) are taught together.
Thus, the rejection under 35 USC 101 is maintained.
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.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-2 and 7 of U.S. Patent No. US 12,542,197 B2 in view of the disclosure of the same. The reference disclosure teaches the importance of invariant descriptors as compounds having the same invariant structures have similar drug efficacies (pg. 11, paragraph [162]). The claims are both directed to the shared field of endeavor of feature quantity calculation and screening, and their combination would be expected to succeed. Therefore, the invention is prima facie obvious.
Reference claim 7 teaches the limitations of claim 1, including storing a first feature quantity, interpreted as similar to the first evaluation value, and making a similar calculation for a ligand which has a confirmed relationship to the target, calculating a similarity, and extracting similar compounds. Reference claim 2, parent to reference claim 7, recites designating a target and quantification calculating by degree of accumulation. Reference claim 1 recites designating a target, generating a three-dimensional structure, calculating a value – interpreted as a feature – based on the structure and binding affinity.
The reference claims do not teach the equations recited in the instant claims, which are found in the specification of the reference claims (paragraphs [144-145]).
Reference claim 2 teaches the limitations of instant claim 2 except that the structure is generated by a plurality of atoms in the generating step, which is disclosed by the reference specification (paragraph [22]).
Instant claim 3 is not taught by the reference claims but is disclosed by the reference specification (paragraph [19]).
Instant claim 3 is not taught by the reference claims but is disclosed by the reference specification (paragraph [155]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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, Olivia M. Wise can be reached at (571) 272-2249. 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.
/Robert J. Kallal/Examiner, Art Unit 1685
Prosecution Insights