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, 6-7, 9, 11, 13, and 30 are pending (claim set as filed on 12/16/2025).
Priority
This application is a 371 of PCT/EP2021/059264 filed on 04/09/2021, which has foreign applications to: EP 20169058.3 and EP 20169071.6 filed on 04/09/2020.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 12/16/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
Withdrawal of Rejections
The response and amendments filed on 12/16/2025 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated herein for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s response to arguments section.
Briefly, the previously applied §112(b) indefiniteness rejection of the phrase “a predetermined threshold level” as a relative terminology has been withdrawn necessitated by Applicant’s persuasive arguments where the specification at ¶ [0166], [0116], & Figure 1 provides guidance to ascertain the scope of the phrase and thereby, not indefinite.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Interpretation
The MPEP 2111.04(II) states that:
II. CONTINGENT LIMITATIONS
The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. For example, assume a method claim requires step A if a first condition happens and step B if a second condition happens. If the claimed invention may be practiced without either the first or second condition happening, then neither step A or B is required by the broadest reasonable interpretation of the claim. If the claimed invention requires the first condition to occur, then the broadest reasonable interpretation of the claim requires step A. If the claimed invention requires both the first and second conditions to occur, then the broadest reasonable interpretation of the claim requires both steps A and B.
In the instant case of amended base claim 1, the recitation of “when the level of HMGB1 is above” and “if said subject has been diagnosed” are conditional phrases and thereby, provides different scopes of the claimed invention. For example, in a first scenario, the level of HMGB1 is above a predetermined threshold to activate an antibiotic treatment step. However, in an alternative second scenario, the level is below a predetermined threshold, then there is no antibiotic necessary. In other words, the latter scenario only requires a determination step under the broadest reasonable interpretation (BRI) because not all the conditions are met or required.
Maintained Rejections
Claim Rejections - 35 USC §101, Subject Matter Eligibility
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 6-7, 9, 11, 13, and 30 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter (based on the 2019 Revised Patent Subject Matter Eligibility Guidance).
STEP 1: Is the claim directed to a process, machine, manufacture, or a composition of matter?
YES, the claims are directed to a process.
STEP 2A: PRONG ONE: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
YES, the claims recite at least one judicially recognized exception(s) of: a law of nature and/or an abstract idea. In particular, the base claim’s recitation of “determining” and “wherein the subject is diagnosed with an atypical bacterial LRTI when the level of HMGB1 is above a predetermined threshold level” denotes the judicial exceptions.
(a) an abstract idea: the recitation of “determining” and “diagnosed” under BRI describes an abstract idea that falls within the mental processes groupings of abstract ideas which are concepts performed in the human mind (including an observation, evaluation, judgment, or opinion).
(b) a law of nature: the second judicial exception describes a correlation or relationship between natural biomarkers and the presence of a respiratory tract infection in the patient. This limitation sets forth a judicial exception, because this type of correlation is a consequence of natural processes (law of nature).
PRONG TWO: Does the claim recite additional elements that integrate the judicial exception into a practical application?
NO, the exception is not integrated into a practical application of the exception. Claim interpretation: as noted in the claim interpretation section above, under BRI, when the level is below a predetermined threshold level, then there is no antibiotic treatment step. Thus, the claims can stop after the judicial exception and thus, it does not apply or use the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition (see Vanda Memo).
STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO, the claimed invention is directed to a law of nature and/or an abstract idea without significantly more. The claim(s) recite(s) determining/diagnosis abstract intangible steps and conditional biomarker levels for LRTI which under BRI describes an abstract idea that falls within the mental processes groupings of abstract ideas which are concepts performed in the human mind (including an observation, evaluation, judgment, or opinion). This judicial exception is not integrated into a practical application because the additional elements of obtaining a sample in order to perform tests is well-understood, routine, and conventional activity for those in the field of diagnostics. Further, the steps are recited at a high level of generality such that it amounts to insignificant pre-solution activity, e.g., a mere data gathering step necessary to use the correlation. The determining, evaluating, and comparative steps are considered various common practices that are routine and conventional activities performed by visual observation, abstract mental analysis, and pathological side by side comparison. Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. The claim here does not invoke any of the considerations that courts have identified as providing significantly more than the exception.
Moreover, the dependent claims are not deemed to qualify as significantly more because they do not add a specific limitation other than what is well-understood, routine, and conventional in the field (in other words, these additional elements presented in the dependent claims are already known and established in the art as evidenced by the prior art as identified below). Therefore, when the additional elements are viewed as an ordered combination, they are not deemed to add meaningful limits on the use of the exception.
Therefore, the claims, as a whole, are considered as processes directed to judicially recognized exceptions without amounting to significantly more from what occurs in nature and thus, are not eligible subject matter under 35 U.S.C. §101.
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 12/16/2025 have been fully considered but they are deemed insufficient to overcome the subject matter eligibility rejection.
In response to Applicant’s argument (addressing page 5 of the remarks) that “the claims now recite a defined method of treatment. There is a specific, concrete therapeutic action that goes beyond the mere observation of a natural correlation”: this argument is not persuasive because, as noted in the claim interpretation section above, the specific concrete therapeutic action is not absolutely required to be practiced under the broadest reasonable interpretation. In other words, the claims have contingent conditional limitations where, if the biomarker level is below the predetermined threshold, then there would be no practical, tangible, or active step of application of the antibiotic treatment. Said differently, in a broad scope, the claims may potentially stop right after the judicial exception step of determining or diagnosing.
In response to Applicant’s argument (addressing page 6 of the remarks) that the “diagnostic step is integrated into a practical application” to the application of specific antibiotics used for the treatment of atypical LRTI: this argument is not persuasive for the reasons reprised from above where the physical application of antibiotic is not required when the level is not above the predetermined threshold.
Maintained Rejections
Claim Rejections - 35 USC §102, Anticipation
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 6-7, 9, 11, 13, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shirakawa (US 2014/0171359 A1).
Shirakawa’s general disclosure relates to a method for detecting respiratory infection associated with bacterial infection (see abstract & ¶ [0001], [0014]).
Regarding base claim 1, Shirakawa teaches “A method for detecting respiratory infection associated with bacterial infection, which comprises the following steps of: 1) measuring CD14-ST in a urine sample derived from a subject; 2) comparing a measured value of CD14-ST in the sample with a normal value; and 3) determining whether the measured value of the sample is higher than the normal value” (see ¶ [0019]-[0022]). Shirakawa teaches “wherein the respiratory infection associated with bacterial infection is lower respiratory tract infection or pneumonia. The method according to any of above (1-1) to (1-8), wherein a differential diagnosis of respiratory infection caused by viral infection is possible”; the causative microorganism includes influenza virus, adenovirus, legionella, chlamydia, mycoplasma, aspergillus, candida, cryptococcus, cytomegalovirus, or pneumococcus, and culture test of blood, sputum or bronchioalveolar lavage fluid (see ¶ [0025]). Shirakawa teaches comparing measured values in samples with a predetermined reference value (see ¶ [0037]-[0038]). Shirakawa teaches “wherein said methods are characterized in that they are able to appropriately select patients with respiratory infection to whom the antibiotic is to be administered, to adjust the administration period of the antibiotic, and to treat respiratory infection associated with bacterial infection” (see abstract).
Regarding claims 1’s limitation and claim 13 pertaining to the biomarkers, Shirakawa teaches the “marker according to above (1-12), further comprising at least one selected from the group consisting of inflammation markers including TNF-α, lactate dehydrogenase, sialic acid, IL-1β, IL-6, and IL-10, markers associated with thrombus and hemostasis including activated partial thromboplastin time, platelet count, fibrinogen, items of the diagnostic criteria for DIC, protein C, D-dimer, thrombin, anti-thrombin III complex, and prothrombin fragment F1+2, infection markers including procalcitonin (PCT), C-reactive protein (CRP), blood urea nitrogen, white blood cell count, endotoxin, adrenomedullin, proadrenomedullin, MR-proADM, B-type natriuretic peptide, trigger receptors expressed on myeloid cell-1, and HMGB1, stress markers including cortisone and copeptin, and markers for interstitial pneumonia including KL-6, SP-A, SP-D, and MCP-1. (1-14). A method for detecting respiratory infection associated with bacterial infection, wherein sCD14-ST in a urine sample derived from a subject and at least one biomarker other than sCD14-ST are measured” (see ¶ [0025], [0070]).
Regarding claims 6-7 pertaining to the symptoms, Shirakawa teaches “a preferred subject is a person suspected to have respiratory infection based on clinical findings. Such clinical findings include at least dyspnea or coughing. In addition, preferred clinical findings include at least one selected from the group consisting of expectoration, chest pain, wheezing, shadow in chest X-ray examination, fever, and white blood cell count” (see ¶ [0063]).
Regarding claims 9 and 11 pertaining to the lower respiratory tract infection, Shirakawa teaches wherein the respiratory infection is lower respiratory tract infection or pneumonia (see ¶ [0031]). The causative microorganism includes influenza virus, adenovirus, legionella, chlamydia, mycoplasma, aspergillus, candida, cryptococcus, cytomegalovirus, or pneumococcus, and culture test of blood, sputum or bronchioalveolar lavage fluid (see ¶ [0025]).
Regarding claim 30 pertaining to the antibiotic, Shirakawa teaches antibiotics that can be applied to at least lower respiratory tract infection and/or pneumonia are preferable. Examples of such include macrolide, new quinolone, or tetracycline antibiotics. One or multiple antibiotics may be appropriately selected (see ¶ [0080]).
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 12/16/2025 have been fully considered but they are not persuasive and deemed insufficient to overcome the prior art of record.
In response to Applicant’s argument (addressing page 6 of the remarks) that “Shirakawa does not teach or suggest a method for the differential diagnosis of atypical bacterial LRTI from typical bacterial LRTI”: this argument is not persuasive because Shirakawa teaches “the causative microorganism test is at least one selected from the group consisting of stained smear test, antigen test of influenza virus, adenovirus, legionella, chlamydia, mycoplasma, aspergillus, candida, cryptococcus, cytomegalovirus, or pneumococcus” (see ¶ [0025]). These causative microorganism overlaps with the atypical bacterial as disclosed by the instant specification of “The atypical group, as second most frequent class of CAP pathogens, is amplifying intracellularly in human cells and usually has no typical bacterial cell wall. Atypical representatives are Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci and Coxiella burnetiid” (see pre-grant specification at ¶ [0010]).
In response to Applicant’s argument (addressing page 7 of the remarks) that “While Shirakawa mentions administering antibiotics generally upon detecting a bacterial infection, it provides no disclosure linking an elevated HMGB1 level to the specific administration of an antibiotic regimen tailored for atypical bacteria (e.g., macrolides, fluoroquinolones or tetracycline antibiotics)”: this argument is not persuasive because Shirakawa teaches antibiotics that can be applied to at least lower respiratory tract infection and/or pneumonia are preferable. Examples of such include macrolide, new quinolone, or tetracycline antibiotics. One or multiple antibiotics may be appropriately selected (see ¶ [0080]).
Conclusion
No claims were allowed.
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 extension fee 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 date of this final action.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653