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 .
Status of the Claims
Claims 1-16 are pending and examined herein.
No claim are canceled.
Priority
As detailed on the 15 October 2024 filing receipt, the application claims priority as early as 09 June 2022 to foreign application KR10-20220070275. 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 statement (IDS) was filed on 12 September 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
Specification
The disclosure is objected to because of the following informality: “has” is misspelled as “ha” (pg. 20, line 6). Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informality: claim 1 recites “culturing the biological sample without treating an anticancer agent” and should likely recite “culturing the biological sample without treating with an anticancer agent”.
Claim Interpretation
Claim 7 recites “a receiving unit” and “an output unit” as part of a system. These elements are recited as part of a computer system and are receiving or outputting data, which are tasks conventionally performed by a general purpose computer and so do not invoke 35 USC 112(f).
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 12-16 are rejected under 35 USC 101 because the claimed invention is directed to non-statutory subject matter. The claims recite “a computer-readable recording medium," which is not, in all embodiments within a broadest reasonable interpretation, interpreted as belonging to any category listed in 101. In a broadest reasonable interpretation, the claim reads on data and/or software comprising no structure other than data and/or software. The claim is not recited as a process, and the claim is not limited to any particular structure as a 101 machine or manufacture. The claim reads on transitory propagating signals which are not proper patentable subject matter because it does not fit within any of the four statutory categories of invention (In re Nuijten, Federal. Circuit, 2006). The specification does not disclose non-transitory embodiments.
Claims 1-16 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 individually and in combination, are directed to a judicial exception at Step 2A, Prong 2, and the additional elements of the claims, considered individually and in combination, do not provide significantly more at Step 2B than the abstract idea of predicting susceptibility to an anticancer agent.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong 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 1-6), a computer system (claims 7-11), and a computer-readable medium (claim 12-16). Claims 1-11 fall within one of the categories of statutory subject matter. Claims 12-16 are non-statutory as they read on transitory propagating signals for the reasons explained above. [Step 1: Claims 1-11: Yes; Claims 12-16: No]
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)).
Claims 1,7, and 12 recite calculating a z-score in treated and untreated scenarios. Calculating a z-score is a mathematical concept.
Claims 1, 7, and 12 recite integrating Z-scores, which is also a mathematical concept.
Claim 1 recites determining if the response is positive or negative, which is considered to be a data evaluation step and thus a step practically performed by the human mind. Claims 7 and 12 recite providing a prediction of susceptibility which is considered to similarly be a mental process of evaluation based on the data.
Claims 4, 8, and 13 recite the equation for calculating an index by integrating the Z-scores and thus recite mental processes.
Claims 5, 9, and 14 recite IC50 and AUC, which are mathematical constructs related to interpreting the drug response derived from the Z-scores.
Claims 6, 10, and 15 recite interpretation of the index, where data interpretation is a mental step.
Claims 11 and 16 recite information about the data received, where data per se is abstract.
Thus, the claims recite abstract ideas and thus must be examined further to determine whether elements in addition to the abstract ideas integrate the judicial exceptions 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))?
Because the claims recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they recite elements in addition to the abstract ideas which integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(III)).
Claim 1 recites culturing a biological sample from a subject and treating the sample with an anticancer agent. Claim 2 recites the sample is a cell sample. Claim 3 recites the sample is three-dimensionally cultured. Claim 7 recites a system, interpreted as a computer system, which receives and outputs data and has a processor. Claim 12 recites a computer-readable medium.
Claims 1-3 recite steps for culturing a sample such that the Z-score and treating a sample with an anticancer agent. These steps are required data gathering steps for performing the Z-score calculations and integration, and as such as interpreted as insignificant extra-solution activity (MPEP 2106.05(g)).
The system, which comprises a processor and elements for receiving and outputting data, is interpreted as general purpose computer. A computer readable medium, if non-transitory, is also considered a computer element. 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)).
Thus, the claims recite elements in addition to the abstract ideas which do not integrate the abstract ideas into a practical application, and must be examined further to determine whether elements in addition to the abstract ideas provide significantly more (MPEP 2106.05). [Step 2A Prong Two: Yes]
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 culturing a biological sample from a subject and treating the sample with an anticancer agent. Claim 2 recites the sample is a cell sample. Claim 3 recites the sample is three-dimensionally cultured. Claim 7 recites a system, interpreted as a computer system, which receives and outputs data and has a processor. Claim 12 recites a computer-readable medium.
Lv (Oncology Letters 14: 6999-7010, 2017; newly cited) teaches three-dimensional cell culturing as a platform for determining drug sensitivity (abstract). Breslin (Drug Discovery Today 18(5/6): 240-249, 2013; newly cited) teaches three-dimensional cell culture in the context of anti-cancer drug screening (abstract). Chaicharoenaudomrung (World Journal of Stem Cells 11(12): 1065-1083, 2019; newly cited) teaches three-dimensional culture systems for drug target identification (abstract) including anticancer screening (Core Tip). Therefore, these steps are considered well-understood, routine, and conventional within the state of the art at the effective filing date.
The claims recite a computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). Storing data on a computer is a conventional computer function (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; MPEP 2106.05(d)). Furthermore, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93 (storing and retrieving information in memory), as discussed in MPEP 2106.05(d)(II)(i)).
Therefore, the recited additional elements, alone or in combination, do not appear to provide an inventive concept. [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.
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 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.
Claims 1-3, 7, 11-12, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Silva (US 20160258931 A1; newly cited) in view of Papagiannakopoulos (US 20210361603 A1; newly cited) and Smith (US 20150018380 A1; newly cited).
Claim 1 recites culturing a biological sample isolated from a subject.
Silva teaches culturing cells from a subject (paragraph [7]).
Claim 1 recites calculating the Z-score (Za) of a drug response factor after treating the
cultured biological sample with an anticancer agent, and calculating the Z-score (Zb) of a cell growth factor by culturing the biological sample without treating an anticancer agent.
Silva teaches determining response of cancer in a subject where an agent has been applied (paragraph [85]) and a tumor growth under control or standard conditions, interpreted as without application of an anticancer drug.
Claim 1 recites determining whether the anticancer agent response is positive or negative
by integrating the calculated Z-score (Za) of the drug response factor and the Z-score (Zb) of the cell growth factor.
Silva teaches an equation relating a growth term and drug exposure in IC50 for determining chemotherapy response (paragraph [132]).
Silva does not teach using a Z-score associated with the metrics.
Papagiannakopoulos teaches standardizing IC50 values, which is a metric of drug response, using a z-score (paragraph [201]).
Smith teaches determining z-scores for cell counts (paragraph [226]).
Claim 7 recites a system, the system comprising a receiving unit which is configured to receive cell experiment-based biological test data for a biological sample isolated from a subject, a processor which is connected to the receiving unit, and an output unit for outputting a result processed by the processor, which performs the calculating and integrating steps of claim 1.
Silva teaches a computer with a processor, input device, and output device (paragraph [96]).
Claim 12 recites a computer readable medium performing the steps of claim 7.
Silva teaches executing instructions stored in tangible, computer-readable media (paragraph [93]).
Claim 2 recites the biological sample is a cell sample isolated from a subject or a cell sample derived from a tissue isolated from a subject.
Silva teaches isolating cells from the sample (paragraph [13]).
Claim 3 recites the cell sample is three-dimensionally cultured in step (a).
Silva teaches 3D reconstruction of the cancer microenvironment (paragraph [10]) and culturing a 3D collagen matrix (paragraph [31]).
Claims 11 and 16 recite the cell experiment-based biological test data comprises test data of at least one of the name of an anticancer agent, the concentration of an anticancer agent, a cell growth rate and the degree of apoptosis.
Silva teaches at least drug names and concentrations of those drugs (paragraph [170]), associated growth rates associated with the drugs (paragraph [170]), and accumulation of cell death due to the drug (paragraph [171]), interpreted as apoptosis.
Combining Silva, Papagiannakopoulos, and Smith
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of Silva, which teaches anti-cancer screening with respect to cell viability and counts, with the z-scores for these metrics as taught by Papagiannakopoulos and Smith because Silva teaches IC50 and tumor growth, while Papagiannakopoulos teaches applying the z-score is a way of standardizing the data for comparison (paragraph [201]) while Smith teaches applying the z-score to determine outliers (paragraph [226]). Both of these are desirable characteristics in biological data normalization, and z-score is a well-known statistical measure. Silva, Papagiannakopoulos, and Smith are all directed to the shared field of endeavor of cancer drug screening and assessment, and their combination would be prima facie obvious.
Claims Free of the Prior Art
Claims 4-6, 8-10, and 13-15 recite or are dependent on claims which recite a specific combination of the drug response and cell growth scores which is not taught or fairly suggested by the considered art such as Silva, Papagiannakopoulos, and Smith, and thus is considered free of the prior art.
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 1-3, 7, 11-12, and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 28-29 and 37-39 of copending Application No. 17/239,118 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application teaches all aspects of the indicated instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 recites culturing a sample, calculating z-scores based on drug response and cell growth, and determining which the response is positive or negative based on the factors.
Reference claim 39 teaches calculating drug response and cell growth z-scores and relating them to determine a prediction regarding drug response.
Culturing the sample is not taught in the method claims of the reference claims but is taught by system claim 28.
Claim 2 recites the biological sample is a cell sample isolated from a subject or a cell sample derived from a tissue isolated from a subject, which is taught by Silva as isolating cells from the sample (paragraph [13]).
Claim 3 recites the cell sample is three-dimensionally cultured, which is taught by Silva as 3D reconstruction of the cancer microenvironment (paragraph [10]) and culturing a 3D collagen matrix (paragraph [31]).
Claim 7 recites a computer system performing the above data processing steps, where claim 39 teaches the data processing steps and the system is taught in reference claim 28.
Claim 12 recites a computer readable medium performing the above steps where claim 39 teaches the data processing steps and the computer readable medium is taught in reference claim 37.
Claims 11 and 16 recite the cell experiment-based biological test data comprises test data of at least one of the name of an anticancer agent, the concentration of an anticancer agent, a cell growth rate and the degree of apoptosis, which is taught by reference claims 29 and 38.
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