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 .
Applicant’s Amendment/Request for Reconsideration-After Non-Final Rejection, filed 3/30/2026, is considered and entered.
Status of Claims
Claims 17 and 20 are cancelled,
Claims 1-15 are withdrawn.
Claims 16, 18-19 and 21-28 are pending and are examined on the merits.
Priority
As detailed on the 7/14/2020 filing receipt, this application claims benefit over a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c). Priority of US application 61/932,156 filed 1/27/2014 is acknowledged.
Withdrawn Rejections/Objections
The objections to claims 16 and 19 in the Office action mailed 02 October 2025 are withdrawn in view of claim amendments filed 3/30/2026. However, new objections are applied.
The rejection to claims 16, 18-19 and 21-26 under 35 U.S.C. 112(a) in the Office action mailed 02 October 2025 is withdrawn in view of claim amendments filed 3/30/2026.
Claim Objections
Claim 16 is objected to because of the following informalities: claim 16 recites “excludes scaffold of drug candidates that do not bind to the 3D intermediate surface net” in the last two lines of step (c), which should read as: “excludes scaffolds of drug candidates that do not bind to the 3D intermediate surface net”.
Claims 21-25 all recite “the 3D pattern matching machine learning algorithm” in their first lines, which should be reconciled with claim 16’s “3D pattern matching algorithm”.
Claim Rejections - 35 USC § 101
The instant rejection is maintained from the previous Office Action filed 11/19/2024 and modified in view of Applicant’s amendments filed 7/15/2025.
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 16, 18-19 and 21-28 are rejected under 35 USC 101 because the claimed inventions are directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture, or Composition of Matter
Independent claim 16 is directed to a method of inhibiting a drug-resistant kinase protein, with steps of "creating”, “screening”, “deconstructing", and “identifying,” so a process.
Step 2A, Prong One: Identification of Judicially Recognized Exceptions
The claim recite:
i) Identifying at least one mutation in a gene encoding a kinase protein in a biologic sample obtained from a subject having cancer, wherein the at least one mutation is a drug-resistance mutation;
This step recites identifying at least one mutation in a gene encoding a kinase protein in a biologic sample obtained from a subject having cancer, which can be achieved in the human mind through comparing two sequences, with perhaps the aid of a pen and paper. Therefore this step equates to an abstract idea of mental processes.
ii) Designing a scaffold of a kinase inhibitor that binds to the drug-resistant kinase protein.
This step recites “designing” in a general way, which is interpreted as an intention. Therefore this step equates to an abstract ideas of mental processes.
a) Creating a three-dimensional fishing net of the distances in a DFG (Aspartate- Phenylalanine-Glycine) intermediate conformation (3D intermediate surface net) of the drug-resistant kinase protein using a 3D pattern matching algorithm, wherein the 3D pattern matching algorithm is trained to (i) receive sequence data of the drug- resistant kinase protein, (ii) apply the received sequence data to a database comprising 3D structure of kinase proteins to determine a 3D structure of the drug-resistant kinase protein, and (iii) align the 3D structure of the drug-resistant kinase protein to a 3D structure of a native kinase protein, thereby predicting the functionality of the drug-resistant kinase protein;
This step recites the “3D pattern matching algorithm”. Since an algorithm is a finite sequence of mathematically rigorous instructions, typically used to solve a class of specific problems or to perform a computation. Algorithms are used as specifications for performing calculations and data processing.
Therefore this step is directed to an abstract idea of mathematical concepts. More specifically, step (i) receive sequence data of the drug-resistant kinase protein is directed to an additional element of acquiring input data; step (ii) apply the received sequence data to a database comprising 3D structure of kinase proteins to determine a 3D structure of the drug-resistant kinase protein is interpreted as predicting protein structure by protein sequence similarity. Such a process will require a way to align and to rank the similar protein sequences. Therefore step (ii) is an abstract idea of mathematical concepts and/or processes that can be achieved by the human mind. Step (iii) align the 3D structure of the drug-resistant kinase protein to a 3D structure of a native kinase protein, thereby predicting the functionality of the drug-resistant kinase protein, which is interpreted as inferring the drug-resistant kinase protein by 3D structural alignment to function known proteins. Such a process will require a way to align and to rank the similar protein structures. Therefore step (iii) is directed to an abstract idea of mathematical concepts and/or processes that can be achieved by the human mind.
b) Screening small fragments from a crystal structure library to capture small fragments that specifically bind to the 3D intermediate surface net of the drug-resistant kinase protein;
This step simulates the binding to 3D intermediate surface net by small fragments, which, under a BRI, requires mathematical modeling of binding energy. This step is therefore directed to an abstract idea of mathematical concepts.
c) Deconstructing the 3D structure of the drug-resistant kinase protein and of the captured small fragments, and constructing a scaffold of a kinase inhibitor drug candidate from the 3D intermediate surface net structure and the captured small fragments using a fragmentation algorithm,
This step reads on a computer simulation process using a fragmentation algorithm. During fragmentation the drug molecule and surrounding receptor pocket are split into distinct functional parts according the disclosure at paragraph [0135]. Spectral clustering algorithm was used in order to split the drug molecules into fragments. “Any ligand can be divided in small parts until we arrive to a single atom. Similarly, the receptor-binding site can be divided in fragments that interact with the ligand until we arrive to a single atom. Using that option we are able to simplify both the ligand and the receptor into functional parts related to the interactions between ligand and receptor” ([0135]). This process can be achieved in human mind with perhaps, the help of paper and a pen. At the end of the process, assessing the binding between the ligand and the receptor will require the calculation of energy status resulted from binding to an ordinary skilled person in art. Therefore, the whole step is directed an abstract idea of mental processes and mathematical concepts.
d) Identifying a scaffold for a drug candidate by searching the crystal structure library, thereby identifying the drug candidate,
This step recites a decision-making process that identifies a scaffold as a drug candidate (implicitly, after some criteria is met). This step therefore equates to an abstract idea of mental processes.
iii) Contacting the drug-resistant kinase protein with the drug candidate, thereby inhibiting the drug-resistant kinase protein.
This step recites a computational simulation of two parts binding and predictions of consequence to the kinase activity. “Contacting” recited in such a general way, reads on a simulation operation to close the distance between the drug candidate and the drug-resistant kinase protein (which can be executed in the human mind). The claim limitation “thereby inhibiting the drug-resistant kinase protein” is interpreted as an intention, which reads on an mental activity. Therefore, this step is directed to an abstract idea of mathematical concepts.
Step 2A Prong Two: Consideration of Practical Application
Claim 16 ends at contacting the drug-resistant kinase protein with the drug candidate “thereby inhibiting the drug-resistant kinase protein”, which is interpreted as an intention, because how contacting the drug resistant protein with a drug candidate inhibits the protein is unknown. Hence this step is classified into an abstract idea of mental processes. Alternatively, doing this step within a molecular modeling platform would be a mathematical operation or simulation. The claimed method steps do not include any additional elements that integrate the recited judicial exceptions into a practical application.
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: “receive sequence data of the drug-resistant kinase protein is directed to an additional element of acquiring input data” (claim 16 step (a)(i)), which is an insignificant extra-solution activity (MPEP § 2106.05(g)). The process steps of the method do not include physical steps of creating any drug or treating any patients with designed medicine. The claimed method steps are based on information having been gathered and organized. The claimed process is therefore drawn to abstract ideas and is a judicial exception, without significantly more.
Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Applicant’ Argument
In the Remarks filed 3/30/2026 (page 9 through page 10), Applicant argued that claim 16 recites a series of steps directed to a process which is a statutory category of invention (Step 1: YES)” (page 11, 1st para). Applicant’s argument refers to Step 1 in the 101 analysis, relating to whether claims falls into one of the four statutory categories. It is true that claim 16 falls into a 101 process, but as discussed above (particularly in the section of Step 2A/Prong One analysis), claim 16 recites judicial exceptions.
In the Remarks (page 11, 2nd para), Applicant argued that the claims also recite the steps in addition to alleged judicial exceptions. Applicant’s argument is not persuasive. The listed steps (emphasis added):
identifying at least one mutation in a gene encoding a kinase protein in a biologic sample obtained from a subject having cancer;
designing a scaffold of a kinase inhibitor that binds to the drug-resistant kinase protein; and
(iii) contacting the drug-resistant kinase protein with the drug candidate.
As discussed above in the 101 rejection, these steps are all classified into abstract ideas of mental processes. Identifying at least one mutation in a gene encoding a kinase protein can easily be achieved in human mind by comparing two gene sequences. Designing a scaffold of a kinase inhibitor that binds to the drug-resistant kinase protein reads on a mental activity; and contacting the drug-resistant kinase protein with the drug candidate reads on an in silico simulation. Doing this step within a molecular modeling platform would be a mathematical operation or simulation. Hence the steps also directed to abstract ideas of mathematical concepts.
In the Remarks (page 11, 3rd para through page 12, 1st para), Applicant argued that:
“as detailed in the specification, the step of identifying at least one drug-resistant mutation in a gene encoding kinase protein in a biologic sample obtained from a subject having cancer requires ’full functional genome sequencing of a novel mutation’ to allow the 3D pattern matching algorithm to create the 3D fishing net of the distances in a DFG intermediate conformation (3D intermediate surface net) of the drug-resistant kinase protein. Then, the designing step includes a deconstructing step, in which the 3D structure of the drug-resistant kinase protein and the captured small fragments are deconstructed and reconstructed using a fragmentation algorithm to simplify the structure of the scaffold of the kinase inhibitor and the structure of the drug-resistant kinase protein into functional parts, which allows the exclusion of scaffold of drug candidates that do not bind to the 3D intermediate surface net of the drug-resistant kinase protein. Applicant submits that those steps integrate any alleged recited judicial exception into practical application, at least because of the use of several algorithms that provide specific solutions to a technical problem.”
In response, Applicant’s argument is not persuasive. We do not read the specification into the claims. There is no step of full genome sequencing recited. The recitation of identifying a mutation of a gene encoding kinase protein (step (i)), is directed to an elements classified into abstract ideas. To integrate claims into a practical application at Step 2A/Prong two, we need additional elements other than judicial exceptions, to apply, to capture and to reflect the judicial exceptions.
In the Remarks (page 12, 2nd para), Applicant argued that “while a human could theoretically perform any software algorithm with enough time, the sheer volume of data or speed required to perform the claimed invention makes manual performance impossible or impractical in a real-world context, rendering the claimed methods impracticable and non-achievable within the human's mind, even with the help of a paper and a pen.”
In response, Applicant’s argument is not persuasive. First in claim examination we applied the broadest reasonable interpretation (BRI) to interpret claim elements, and under a BRI the claim elements are not necessarily recite large volume of data; Second, it is important to explain that analyzing a lot of data does not augment the steps being performed to analyze the data, which are abstract ideas. Computations on a lot of data performed mentally, or with paper and pencil, would take considerable time and effort, but that is, of course, the singular purpose of computers and computer networks, to perform large numbers of calculations, via algorithms, rapidly, and without error (assuming no error in user input). Although a general purpose computer can perform calculations at a rate and accuracy that can far outstrip the mental performance of a skilled artisan, the nature of the activity is essentially the same, and constitutes an abstract idea. See Bancorp Serves., L.L. C. v. Sun Life Assur. Co. of Canada (U.S.), 687 F.3d 1266,1278 (Fed. Cir. 2012) (holding that “the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter”); see also See SiRF Tech., Inc. v. Int’l Trade Comm ’n, 601 F.3d 1319,1333 (Fed. Cir. 2010) (holding that: In order for the addition of a machine to impose a meaningful limit on the scope of a claim, it must play a significant part in permitting the claimed method to be performed, rather than function solely as an obvious mechanism for permitting a solution to be achieved more quickly, i.e., through the utilization of a computer for performing calculations).
In the Remarks (page 12, 3rd para), Applicant argued that “the claims require the step of contacting the drug-resistant kinase protein with the drug candidate, this validation step aims at confirming that the drug candidate inhibits the drug-resistant kinase protein. As detailed throughout the specification, validation can include the use of thermal shift calorimetric (TSA) and surface plasmon resonance (SPR), and/or ultimately, the administration of the drug candidate to the subject with cancer (see specification at paragraphs [0153], [0154] and [0017], [0020] and [0092] for example)”
In response, Applicant’s argument is not persuasive. Examiner has to separate the specification from the claimed language. Under a BRI, the argued element is interpreted as a in silico simulation of two parts binding and predictions of consequence to the kinase activity. “Contacting” recited in such a general way, reads on a simulation operation to close the distance between the drug candidate and the drug-resistant kinase protein. This step within a molecular modeling platform would be a mathematical operation or simulation. Hence the steps are also directed to abstract ideas of mathematical concepts. The claim limitation “thereby inhibiting the drug-resistant kinase protein” is interpreted as an intention, which reads on an mental activity. Therefore, this step is directed to an abstract idea of mathematical concepts and mental processes.
In the Remarks (page 12, penultimate para), Applicant argued that “any recited judicial exception is applied, relied on and used in a manner that imposes meaningful limit on the judicial exception, and is therefore integrated into practical application (STEP 2A, Prong Two: YES). Accordingly, Applicant submits that the claims are not directed to a judicial exception (STEP 2A: NO) and are patent eligible.”
In response, Applicant’s argument is not persuasive. For the whole instant claim set, the only identified additional element is claim 16 step (a)(i) “receive sequence data of the drug-resistant kinase protein is directed to an additional element of acquiring input data”, which is an insignificant extra-solution activity. The process steps of the method do not include any additional elements to apply, to capture and to reflect the judicial exceptions. therefore the claims are not integrated into a practical application at Step 2A/Prong two.
Therefore, the 35 USC 101 rejection is maintained.
Double Patenting
The instant rejection is maintained from the previous Office Action filed 11/19/2024 and modified in view of Applicant’s amendments filed 7/15/2025.
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 16-19 and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-19 and 15 of co-pending Application No. 17921477 in view of Liao ("Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors." Journal of medicinal chemistry 50.3 (2007): 409-424. Previously Cited), in view of Gani ("Evaluating the Predictivity of Virtual Screening for Abl Kinase Inhibitors to Hinder Drug Resistance." Chemical Biology & Drug Design 82.5 (2013): 506-519. Previously cited).
This is a provisional nonstatutory double patenting rejection.
The newly amended claim 16 includes limitations that are not recited in the reference claim 16. However, the newly added parts are obvious over Gani, Specifically, Gani provides “Several methods (multiple linear regression, PLS regression, and neural network regression) were used to create models for predicting the experimental binding affinity (pIC50) from molecular properties. Even in the absence of clear correlations with individual molecular properties, such models can in principle be trained to recognize complex multifactorial patterns, given enough data. Here, the neural network–based regression provided the best correlation between the experimental and predicted values (Figure 7)” (page 513, col 2, last para through page 514, col 1, 1st para), which teaches pattern match and machine learning for therapeutic regimen design.
It would have been prima facie obvious to modify the reference kinase inhibitor design pipeline using short fragment screening around the 3D surface net which has the pattern matching component with Gani’s pattern match machine learning algorithm (Gani: page 513, col 2, last para through page 514, col 1, 1st para), because “The network then recognizes the patterns seen during training and retains the ability to generalize and recognize similar, but non-identical patterns” (Gani: page 511, col 2, last para last three lines. Here the “network” refers the “Neural network”).
One would expect success as both the reference invention and Gani are about kinase inhibitor design based on the target 3D surface net structure and Gani demonstrated that “Even in the absence of clear correlations with individual molecular properties, such models can in principle be trained to recognize complex multifactorial patterns, given enough data. Here, the neural network–based regression provided the best correlation between the experimental and predicted values (Figure 7)” (Gani: page 514, col 1, last para last seven lines; and page 516, Fig. 7).
Response to Applicant’s Arguments
In the Remarks filed 3/30/2026, Applicant requests the ODP rejection “be held in abeyance until claims are otherwise determined to be allowable” (page 13 2nd para). Applicant’s request is acknowledged.
Conclusion
No claims are 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 GUOZHEN LIU whose telephone number is (571)272-0224. The examiner can normally be reached Monday-Friday 8-5.
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, Larry D Riggs can be reached at (571) 270-3062. 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.
/GL/
Patent Examiner
Art Unit 1686
/Anna Skibinsky/
Primary Examiner, AU 1635
Prosecution Insights