Notice of 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 .
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 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.
Withdrawal of Objections and Rejections
Applicant's response, filed 07/16/2026, has been fully considered.
In view of the amendment and remarks, the objection to the claims and the rejection of the following claims are withdrawn:
claims 9-15 under 35 USC § 112(a);
claims 9-15 under 35 USC § 112(b);
claim 10 under 35 U.S.C. § 101;
claim 10 under 35 USC § 103.
The following rejections and/or objections are either maintained or newly applied for claims 9 and 11-15. They constitute the complete set applied to the instant application. Herein, "the previous Office action" refers to the Non-Final Rejection of 04/17/2026.
Status of the Claims
Claim 10 is canceled.
Claims 9 and 11-15 are pending.
Claims 1-8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, as set forth in the Non-Final Office Action dated 04/17/2026.
Claims 9 and 11-15 are rejected.
Priority
This application US 18/154,906 (01/16/2023) claims priority from Foreign Application TW111132547 (08/29/2022), as reflected in the filing receipt mailed on 02/07/2023. The claims to the benefit of priority are acknowledged and the effective filing date of claims 9 and 11-5 is 08/29/2022.
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 9 and 11-15 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas..., 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)). Any newly recited portions are necessitated by claim amendment.
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
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)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a system (claims 9 and 11-15); which falls within one of the categories of statutory subject matter. [Step 1: claims 9 and 11-15: 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))?
Background
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)).
Analysis of instant claims
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims found to recite abstract ideas that can fall into the grouping of mathematical concepts (in particular mathematical relationships and formulas) and mental processes (in particular procedures for observing, analyzing and organizing information). The identified grouping(s) for this instant claims are as follows:
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include:
• "assess whether the Klebsiella pneumoniae is resistant to a carbapenem antibiotic or a colistin or not … wherein when the Klebsiella pneumoniae is resistant to the carbapenem antibiotic, the feature set of the target mass spectrum data comprises a first anti-carbapenem feature mark, a mass-to-charge ratio of the first anti-carbapenem feature mark ranges from 4,520 to 4,529 daltons, and the Klebsiella pneumoniae comprises a Klebsiella pneumoniae carbapenemase; wherein when the Klebsiella pneumoniae is resistant to the colistin, the feature set of the target mass spectrum data comprises a first anti-colistin feature mark, and a mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons" (independent claim 9).
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind (i.e. concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) or because the method only requires a user to manually determine action based on an added number. Under the BRI, the recited limitations are mental processes because a human mind is also sufficiently capable of analyzing a data set to pick features to assess whether the Klebsiella pneumoniae is resistant to an antibiotic or not by determining if a mass-to-charge ratio falls within a range.
Dependent claims 2, 4-5, 8-9, 11, 16-17, 20, 31-32 and 34 recite further steps that limit the judicial exceptions in independent claim 9 and, as such, also are directed to those abstract ideas. For example, claims 2, 5, and 17 recite further details about the simulated molecular interactions involved in inflammation; claims 4, 16, and 31-32 recite further details about the type of molecules simulated; claims 8-9, 20 and 34 recite further details about the transcriptomics data and claims 29-30 recite further details about the motif identification.
[Step 2A Prong One: claims 9 and 11-15: 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))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using 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, as discussed in MPEP § 2106.05(e).
Analysis of instant claims
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2).
Instant claim 9 recites additional elements that are not abstract ideas:
• "a non-transitory machine readable medium for storing a target mass spectrum data, wherein the target mass spectrum data was obtained by detecting a test sample with a mass spectrometry method, and the test sample comprises a Klebsiella pneumoniae” (independent claim 9);
• "a processor signally connected to the non-transitory machine readable medium, wherein the target mass spectrum data is analyzed by the processor so as to output a feature set" (independent claim 9);
Dependent claims 11, 13 and 15 recite further details about the feature set. Dependent claims 12 and 14 recite further details about the target mass spectrum data.
Considerations under Step 2A, Prong Two
The limitations recited in claim 9 are interpreted as requiring the use of a computer. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions or instructions to implement on a generic computer.
Further steps directed to additional non-abstract elements of a computing device/computer do not describe any specific computational steps by which the "computer parts" perform or carry out the judicial exceptions, 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 a generic computer which performs the functions that constitute judicial exceptions.
The judicial exceptions in the claims are considered to perform the claimed abstract idea with a computer, which is not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and merely performing the mental process in a computer environment do not negate the fact that something that can be carried out in the human mind. See MPEP 2106.04(a)(2).III.C. Additionally, claims 1-10 and 16-20 do not recite an additional element, and therefore there is nothing in the claims to provide a practical application at Step 2A, Prong 2, or significantly more at Step 2B.
The recited "detecting a test sample with a mass spectrometry" and " storing a target mass spectrum data" read on data gathering activities; not amounting to a practical application. The type of data doesn’t change that it is mere data gathering or conventional computer receiving means. Dependent claims limitations constitute mere data gathering activity because recite details about information that is used as input to the judicial exceptions.
Claims directed to "to output a feature set" read on receiving or transmitting data over a network -Symantec, 838 F.3d at 1321 - MPEP 2106.05(a) pertains; which constitutes just necessary data gathering and therefore correspond to insignificant extra-solution activity.
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)).
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
[Step 2A Prong Two: claims 9 and 11-15: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
Claim 9 recites a computer or computer functions, 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)).
Further, the courts have found that receiving/storing and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a 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), Versa ta 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, as discussed in MPEP 2106.05(d)(Il)(i)).
With respect to the instant claims, the prior art review to Yoon ("MALDI-TOF mass spectrometry technology as a tool for the rapid diagnosis of antimicrobial resistance in bacteria." Antibiotics 10.8:982 (2021), newly cited) discloses that detecting a test sample with a mass spectrometry is routine, well-understood and conventional in the art. Said portions of the prior art are, for example, pg. 9 Table 1.
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h).
The instant claims constitute insignificant extra solution activity, and when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(g)). Hence, these elements, when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(d)).
[Step 2B: claims 9-15: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For the reasons above, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept not clearly anything significantly more.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 101
The Remarks of 007/16/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 13 para. 5:
As shown in Part "Claim Rejections - 35 USC § 103" of the present response, all of HUANG to ALIZADEH fail to disclose the features "a mass-to-charge ratio of the first anti-carbapenem feature mark ranges from 4,520 to 4,529 daltons" and "a mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons" of the amended claim 9 of the present application, and under the features "a mass-to-charge ratio of the first anti-carbapenem feature mark ranges from 4,520 to 4,529 daltons" and "a mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons" of the amended claim 9, the accuracy of the drug-resistant Klebsiella pneumoniae assessing system is significantly increased, and the drug-resistant Klebsiella pneumoniae assessing system of the amended claim 9 can be used to assess whether the Klebsiella pneumoniae is resistant to a carbapenem antibiotic or a colistin or not. Accordingly, it is hard and not obvious for the person skilled in the art to combine the features of HUANG to ALIZADEH so as to obtain the drug-resistant Klebsiella pneumoniae assessing system of the amended claim 9 as well as to predict the efficiency thereof. Furthermore, by all the features of the amended claim 9, the drug-resistant Klebsiella pneumoniae assessing system of the amended claim 9 can be used to predict the carbapenem antibiotic-resistant Klebsiella pneumoniae including the Klebsiella pneumoniae carbapenemase or the colistin-resistant common Klebsiella pneumoniae in clinical practice effectively so as to facilitate the clinical diagnosis and medication of the doctors. Thus, the present application exactly includes an inventive concept and can be practically applied in related filed, so that the claimed invention of the present application is NOT directed to a judicial exception without significantly more and should be patentable over 35 U.S.C. § 101. Applicant respectfully requests withdrawal of this basis of rejection
It is respectfully submitted that this is not persuasive because the limitation “to assess (i.e. the argued “to predict” is not a claim recitation) whether the Klebsiella pneumoniae is resistant to a carbapenem antibiotic or a colistin or not” pointed by the Applicant is considered to recite a judicial exception as described above and are therefore not considered at Step 2B for significantly more considerations under 35 U.S.C. § 101 .
Regarding the remarks under the header labeled “Claim Rejections - 35 U.S.C. § 101”, the Applicant appears to be conflating considerations at 35 U.S.C. § 101 STEP 2B by arguing “the present application is NOT directed to a judicial exception without significantly more and should be patentable over 35 U.S.C. § 101 – with considerations under 35 U.S.C. § 103 by arguing “Accordingly, it is hard and not obvious for the person skilled in the art to combine the features of HUANG to ALIZADEH so as to ..”
Regarding considerations under 35 U.S.C. § 101 STEP 2B, obviousness is not a factor considered. Obviousness of claim elements are only considered under 35 U.S.C. § 103.
35 U.S.C. § 101 STEP 2B instructs that an inventive concept cannot be provided the by judicial exception. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)).
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
A. Claims 9, 11, 13 and 15 are rejected under 35 U.S.C. 103(a) as being unpatentable over Huang ("Detection of carbapenem-resistant Klebsiella pneumoniae on the basis of matrix-assisted laser desorption ionization time-of-flight mass spectrometry by using supervised machine learning approach." PLoS One 15(2):e0228459 (2020) – cited on the 04/17/2026 Form PTO-892) in view of Giordano ("Rapid detection of colistin-resistant Klebsiella pneumoniae using MALDI-TOF MS peak-based assay." Journal of microbiological methods 155:27-33 (2018) – newly cited). The instant rejection is newly stated and is necessitated by claim amendment.
Claim 9 recites:
a non-transitory machine readable medium for storing a target mass spectrum data,
wherein the target mass spectrum data was obtained by detecting a test sample with a mass spectrometry method, and the test sample comprises a Klebsiella pneumoniae; and
a processor signally connected to the non-transitory machine readable medium, wherein the target mass spectrum data is analyzed by the processor so as to output a feature set to assess whether the Klebsiella pneumoniae is resistant to a carbapenem antibiotic or a colistin or not;
wherein when the Klebsiella pneumoniae is resistant to the carbapenem antibiotic, the feature set of the target mass spectrum data comprises a first anti-carbapenem feature mark, a mass-to-charge ratio of the first anti-carbapenem feature mark ranges from 4,520 to 4,529 daltons, and the Klebsiella pneumoniae comprises a Klebsiella pneumoniae carbapenemase
• Huang teaches the application of machine learning for differentiation of drug resistant bacteria from susceptible ones by directly using the profile spectra of whole cells MALDI-TOF MS in Carbapenem-resistant Klebsiella pneumoniae (i.e. wherein the target mass spectrum data was obtained by detecting a test sample with a mass spectrometry method, and the test sample comprises a Klebsiella pneumoniae) (pg. 1 para. 1) and computer algorithms (i.e. non-transitory machine readable medium) (pg. 9 Table 2) for classification of MALDI-TOF MS data (pg. 3 para. 5); wherein the MALDI-TOF MS reliably differentiates Carbapenem‑Resistant Klebsiella pneumoniae from Carbapenem‑Sensitive Klebsiella pneumoniae (pg. 10 para. 1) (i.e. wherein the target mass spectrum data is analyzed by the processor so as to output a feature set to assess whether the Klebsiella pneumoniae is resistant to a carbapenem antibiotic or a colistin or not); wherein a two-step strategy for data preprocessing consisting of peak and a feature selection step (i.e. comprising multiple possible feature marks) is used before supervised machine learning analysis (pg. 1 para. 2); wherein samples were analyzed in linear positive-ion mode and at a laser frequency of 50 Hz across the mass-to-charge ratio range of 2,000 to 20,000 daltons (i.e. wherein when the Klebsiella pneumoniae is resistant to the carbapenem antibiotic, the feature set of the target mass spectrum data comprises a first anti-carbapenem feature mark, a mass-to-charge ratio of the first anti-carbapenem feature mark ranges from 4,520 to 4,529 daltons) (pg. 4 para. 3); wherein among the 46 Carbapenem‑Resistant Klebsiella pneumoniae, 29 (63.0%) were detected as carbapenemase (i.e. Klebsiella pneumoniae comprises a Klebsiella pneumoniae carbapenemase) (pg. 6 para. 7).
• Huang teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of 4,520 to 4,529 daltons. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
wherein when the Klebsiella pneumoniae is resistant to the colistin, the feature set of the target mass spectrum data comprises a first anti-colistin feature mark, a mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons
• Huang does not teach the recitation above. However, Giordano teaches the rapid detection of colistin-resistant Klebsiella pneumoniae using MALDI-TOF
MS peak-based assay (pg. 27 Title); wherein colistin-resistant Klebsiella pneumoniae marker peaks were found at 4171,05 Da (pg. 30 Table 3) (i.e. a mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons)
Claim 11 recites:
wherein the feature set further comprises a second anti-carbapenem feature mark, and when the Klebsiella pneumoniae is resistant to the carbapenem antibiotic, the target mass spectrum data further comprises the second anti-carbapenem feature mark, and a mass- to-charge ratio of the second anti-carbapenem feature mark ranges from 6,150 to 6,159 daltons
• Huang teaches the analysis of antibiotics and their degradation products (pg. 2 para. 2); wherein carbapenemases may confer resistance to virtually all available beta-lactam antibiotics such as in the most frequent carbapenemases – Klebsiella pneumoniae carbapenemase enzymes; which KPC-producing bacteria are mostly in the form of K. pneumoniae. (pg. 2 para. 1); wherein the presence of carbapenemases was confirmed by the detection of carbapenem hydrolysis (pg. 2 para. 2); wherein samples were analyzed in linear positive-ion mode and at a laser frequency of 50 Hz across the mass-to-charge ratio range of 2,000 to 20,000 daltons (i.e. identified mass-to-charge ratio ranging from 6,150 to 6,159 daltons) (pg. 4 para. 3); wherein a two-step strategy for data preprocessing consisting of peak matching and a feature selection step (i.e. feature mark) is used before supervised machine learning analysis (i.e. an analyzing module for analyzing the target mass spectrum data by a drug susceptibility analysis program) (pg. 1 para. 2); wherein significant peaks with top ranking according to the p-value were selected as input features to construct classifier (i.e. selection of feature marks) (pg. 10 para. 3).
• Huang teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of 6,150 to 6,159 daltons. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
Claim 13 recites:
wherein the feature set further comprises a third anti-carbapenem feature mark, and when the Klebsiella pneumoniae is resistant to the carbapenem antibiotic, the target mass spectrum data further comprises the third anti-carbapenem feature mark, and a mass-to- charge ratio of the third anti-carbapenem feature mark ranges from 2,180 to 2,189 daltons
• Huang teaches the analysis of antibiotics and their degradation products (pg. 2 para. 2); wherein carbapenemases may confer resistance to virtually all available beta-lactam antibiotics such as in the most frequent carbapenemases – Klebsiella pneumoniae carbapenemase enzymes; which KPC-producing bacteria are mostly in the form of K. pneumoniae. (pg. 2 para. 1); wherein the presence of carbapenemases was confirmed by the detection of carbapenem hydrolysis (pg. 2 para. 2); wherein samples were analyzed in linear positive-ion mode and at a laser frequency of 50 Hz across the mass-to-charge ratio range of 2,000 to 20,000 daltons (i.e. identified mass-to-charge ratio ranging from 6,150 to 6,159 daltons) (pg. 4 para. 3); wherein a two-step strategy for data preprocessing consisting of peak matching and a feature selection step (i.e. feature mark) is used before supervised machine learning analysis (i.e. an analyzing module for analyzing the target mass spectrum data by a drug susceptibility analysis program) (pg. 1 para. 2); wherein significant peaks with top ranking according to the p-value were selected as input features to construct classifier (i.e. selection of feature marks) (pg. 10 para. 3).
• Huang teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of 2,180 to 2,189 daltons. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
Claim 15 recites:
wherein the feature set further comprises a second anti-colistin feature mark, and when the Klebsiella pneumoniae is resistant to the colistin, the target mass spectrum data further comprises the second anti-colistin feature mark, and a mass-to-charge ratio of the second anti-colistin feature mark ranges from 7,320 to 7,329 daltons
• Huang teaches the analysis of antibiotics and their degradation products (pg. 2 para. 2); wherein carbapenemases may confer resistance to virtually all available beta-lactam antibiotics such as in the most frequent carbapenemases – Klebsiella pneumoniae carbapenemase enzymes; which KPC-producing bacteria are mostly in the form of K. pneumoniae. (pg. 2 para. 1); wherein the presence of carbapenemases was confirmed by the detection of carbapenem hydrolysis (pg. 2 para. 2); wherein samples were analyzed in linear positive-ion mode and at a laser frequency of 50 Hz across the mass-to-charge ratio range of 2,000 to 20,000 daltons (i.e. identified mass-to-charge ratio ranging from 6,150 to 6,159 daltons) (pg. 4 para. 3); wherein a two-step strategy for data preprocessing consisting of peak matching and a feature selection step (i.e. feature mark) is used before supervised machine learning analysis (i.e. an analyzing module for analyzing the target mass spectrum data by a drug susceptibility analysis program) (pg. 1 para. 2); wherein significant peaks with top ranking according to the p-value were selected as input features to construct classifier (i.e. selection of feature marks) (pg. 10 para. 3).
• Huang teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of 7,320 to 7,329 daltons. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
Rationale for combining (MPEP §2142-2143)
Regarding claims 9, 11, 13 and 15, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Huang in view of Giordano because all references disclose methods for the investigation of antimicrobial resistance in Klebsiella pneumoniae. The motivation would have been to incorporate rapid preliminary results on colistin resistance profile coupled with bacteria identification (pg. 27 Abstract Giordano).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the antimicrobial resistance in Klebsiella pneumoniae analysis method of Huang to the methods by Giordano because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the investigation of antimicrobial resistance in Klebsiella pneumoniae.
Regarding the recited first/second/third anti-carbapenem feature mark and first/second colistin feature mark, the "feature selection step" taught by Huang can be modified to select each of the recited features taught by Huang and Giordano as described above. One of ordinary skill in the art would be motivated to select a different feature for routine optimization reasons for determination of the optimum or workable ranges. MPEP 2144.05 II states - The Supreme Court has clarified that an "obvious to try" line of reasoning may properly support an obviousness rejection. In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because "obvious to try" is not a valid rationale for an obviousness finding. Another motivation to combine the teachings originates from the "obvious to optimize" 2144.05 rationale, which states that choosing from a finite number of identified, predictable solutions (i.e., in this case a finite number of feature marks), with a reasonable expectation of success would motivate one of ordinary skill in the art. See MPEP 2143 (I). See MPEP 2144.05 (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art").
B. Claims 12 and 14 are rejected under 35 U.S.C. 103(a) as being unpatentable over Huang and Giordano as applied to claim 9 above further in view of Alizadeh ("Molecular characteristics of carbapenem-resistant Klebsiella pneumoniae isolates producing blaVIM, blaNDM, and blaIMP in clinical centers in Isfahan, Iran." Jundishapur J. Microbiol 14(2):e114473 (2021)), as cited on the 04/17/2026 Form PTO-892. The instant rejection is newly stated and is necessitated by claim amendment.
Claim 12 recites:
wherein when the target mass spectrum data comprises the second anti-carbapenem feature mark, the Klebsiella pneumoniae comprises a metallo-β-lactamases, and the metallo-β-lactamase is imipenemase metallo-β-lactamases, New Delhi metallo-β-lactamases, or Verona integron-encoded metallo-β-lactamases
• Neither Huang or Giordano teach the recitation above. However, Alizadeh teaches the investigation of metallo-β-lactamases production among Klebsiella pneumoniae isolates including mechanisms of carbapenem resistance including Verona Integron-encoded Metallo-beta-lactamase (VIM), imipenemase (IMP), and New Delhi metallo-beta-lactamase (NDM) (pg. 2 col. 1 para. 2).
Claim 14 recites:
wherein when the target mass spectrum data comprises the third anti-carbapenem feature mark, the Klebsiella pneumoniae comprises an oxacillinase-type carbapenemase, and the oxacillinase-type carbapenemase is OXA-48-like carbapenemases
• Neither Huang or Giordano teach the recitation above. However, Alizadeh teaches the investigation of Klebsiella pneumoniae producing isolates wherein Klebsiella pneumoniae was identified to represent a single locus variant of ST14 and is currently widely disseminated among OXA-48 (i.e. oxacillinase-type carbapenemase is OXA-48-like carbapenemases), and NDM-1- producing K. pneumoniae isolates (pg. 10 col. 1 para. 2).
Rationale for combining (MPEP §2142-2143)
Regarding claims 12 and 14, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Huang and Giordano in view of Alizadeh because all references disclose methods for the investigation of antimicrobial resistance in Klebsiella pneumoniae. The motivation would have been to identify the presence of important virulent factors in the development of infections through Klebsiella pneumoniae (pg. 10 col. 2 para. 1 Alizadeh).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the antimicrobial resistance in Klebsiella pneumoniae analysis method of Huang and Giordano to the methods by Alizadeh because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the investigation of antimicrobial resistance in Klebsiella pneumoniae.
Regarding the recited first/second/third anti-carbapenem feature mark, the "feature selection step" taught by Huang can be modified to select each of the recited features taught by Huang, Giordano and Alizadeh described above. One of ordinary skill in the art would be motivated to select a different feature for routine optimization reasons for determination of the optimum or workable ranges. MPEP 2144.05 II states - The Supreme Court has clarified that an "obvious to try" line of reasoning may properly support an obviousness rejection. In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because "obvious to try" is not a valid rationale for an obviousness finding. Another motivation to combine the teachings originates from the "obvious to optimize" 2144.05 rationale, which states that choosing from a finite number of identified, predictable solutions (i.e., in this case a finite number of feature marks), with a reasonable expectation of success would motivate one of ordinary skill in the art. See MPEP 2143 (I). See MPEP 2144.05 (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art").
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 103
The Remarks of 07/16/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 16 para. 3:
However, although Huang has disclosed the mass-to-charge ratio range used in the MALDI-TOF MS, Huang still fails to disclose the mass-to-charge ratio ranges of the first anti-carbapenem feature mark limited within 4,520 to 4,529 daltons and the first anti-colistin feature mark limited within 4,170 to 4,179 daltons. Accordingly, Huang fails to disclosure the features "a mass-to-charge ratio of the first anti-carbapenem feature mark ranges from 4,520 to 4,529 daltons" and "a mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons" of the amended claim 9 of the present application.
Further, according to the disclosures of Holt and Alizadeh, both of Holt and Alizadeh also fail to disclose the features "a mass-to-charge ratio of the first ant carbapenem feature mark ranges from 4,520 to 4,529 daltons" and "a mass-to charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 … "[0093] As shown in Fig. 10, based on the results of SHAP method, the peak of Feature mark 4170 (the mass-to-charge ratio thereof ranges from 4, 170 to 4,179 daltons) has the highest SHAP value, the peak of Feature mark 7320 (the mass-to-charge ratio thereof ranges from 7,320 to 7,329 daltons) has the next highest SHAP value, and thus Feature mark 4170 and Feature mark 7320 are respectively used as the first anti-colistin feature mark and the second anti-colistin feature mark
As shown in Paragraphs [0085], [0093] and Figs. 5, 10 of the present application, when the mass-to-charge ratio of the first anti-carbapenem feature mark ranges from 4,520 to 4,529 daltons, the assessment of the carbapenem antibiotic resistant Klebsiella pneumoniae based on the first anti-carbapenem feature mark has highest accuracy, and when the mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons, the assessment of the colistin resistant Klebsiella pneumoniae based on the first anti-colistin feature mark has highest accuracy, Therefore, it shows that by selecting the first anti-carbapenem feature mark and the first anti-colistin feature mark with the mass-to-charge ratio respectively ranging from 4,520 to 4,529 daltons and 4,170 to 4,179 daltons, the drug-resistant Klebsiella pneumoniae assessing system of the present disclosure can be used to effectively assess whether the Klebsiella pneumoniae of the test sample is resistant to the carbapenem antibiotic or the colistin or not, so the drug-resistant Klebsiella pneumoniae assessing system of the amended claim 9 of the present application can effectively assess whether the Klebsiella pneumoniae is resistant to the carbapenem antibiotic or the colistin or not based on that whether the mass spectrum data of the Klebsiella pneumoniae includes the first anti-carbapenem feature mark or the first anti-colistin feature mark. Accordingly, the time required for the conventional microbial culture, the identification and the antibiotic susceptibility testing can be effectively reduced, and it is favorable for formulating the medical strategy for the drug-resistant Klebsiella pneumoniae, and the present disclosure has the potential application in clinical.
It is respectfully submitted that this is not persuasive because the claimed mass-to-charge ratio range for the identification of each marker overlapped or was taught by values in the prior art – the level of accuracy or details from shown in Paragraphs [0085], [0093] and Figs. 5, 10 of the present application regarding the claimed invention are not aspects recited in the claims and therefore not under examination. MPEP 2173.05(b) pertains - "though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim" (Superguide Corp. v. DirecTV Enterprises, Inc., 69 USPQ2d 1865 at 1868 (CAFC 2004)). Hence, Appellant's arguments are predicated on an interpretation that is inconsistent with the broadest reasonable interpretation of the claim scope.
Regarding the first anti-carbapenem feature mark, Huang teaches the application of machine learning for differentiation of drug resistant bacteria from susceptible ones by directly using the profile spectra of whole cells MALDI-TOF MS in Carbapenem-resistant Klebsiella pneumoniae wherein samples were analyzed in linear positive-ion mode and at a laser frequency of 50 Hz across the mass-to-charge ratio range of 2,000 to 20,000 daltons – which overlaps with the claimed range from 4,520 to 4,529 daltons. Overlapping ranges are considered as sufficient suggestion over the prior art. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir.1990). Note MPEP 2144.05.
Regarding the first anti-colistin feature mark, the newly cited art to Giordano teaches the rapid detection of colistin-resistant Klebsiella pneumoniae using MALDI-TOF MS peak-based assay (pg. 27 Title); wherein colistin-resistant Klebsiella pneumoniae marker peaks were found at 4171,05 Da (pg. 30 Table 3) (i.e. a mass-to-charge ratio of the first anti-colistin feature mark ranges from 4,170 to 4,179 daltons).
Due to the described reasons above, it is interpreted that the claims do not patentably distinguish the claimed invention from the teachings found in the prior art. Furthermore, in this instant application, the amendments support existing claim rejections, in which the recited limitations are all addressed, see Claim Rejections above.
Conclusion
No claims are allowed.
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.
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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
