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 Claims
Claims 23 and 34-39 were pending. Claims 34, 37, and 38 are canceled. Claims 23 and 35 are amended.
Claims 23, 35, 36, and 39 are examined herein.
Claim Objections
Claim 35 is objected to because of the following informalities:
Claim 35 contains abbreviation NEWS. Abbreviations should be completely spelled out in their first occurrence.
Appropriate correction is required.
Withdrawn Rejections
The rejections of claims 23, 35, 36, and 39 under 35 U.S.C. 112(b) is withdrawn in view of claims 23 and 35 amendments. However, claim 35 amendment necessitated another rejection under 35 U.S.C. 112(b).
The rejections of claims 34, 37, and 38 are withdrawn in view of claims cancellation.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL. —The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 23, 35, 36, and 39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 23 recites diagnosing the patient to have a bacterial and/or viral infection based on said level of PCT being above 0.25 ng/mL and treating said patient with an antibiotic agent and/or anti-viral compound based on said level being above 0.25 ng/mL.
The prior art does not teach diagnosing the patient to have a bacterial and/or viral infection based on said level of PCT being above 0.25 ng/mL and treating said patient with an antibiotic agent and/or anti-viral compound based on said level being above 0.25 ng/mL.
However, the specification fails to disclose steps of actually identifying/diagnosing the patient condition as an infection on the bases of PCT measurements. The PCT biomarker is disclosed in the specification as an optional biomarker:
“According to the present invention proADM and optionally PCT and/or other markers or clinical scores are employed as markers for the diagnosis, prognosis, prediction, risk assessment and/or risk stratification of a patient in developing a medical condition that requires treatment in hospital who presents with symptoms of an infectious disease” (pg. 25, lines 23-26);
“Kit comprises detection reagents for determining the level proADM or fragment(s) thereof, and optionally additionally for determining the level of PCT” (pg. 30, lines 9-10), “The levels of ADM and optionally other markers such as PCT” (line 24), and “sample to which the level of ADM and optionally PCT” (line 28).
Moreover, the PCT biomarker is not disclosed in the specification in association with (a) diagnosing the patient to have a bacterial and/or viral infection based on the measured level of PCT or (b) treating said patient with an antibiotic agent and/or anti-viral compound.
The specification discloses PCT only in general terms, for example:
“combined measurement of additional biomarkers, in particular PCT, enables improved prognosis and/or further indications on the extent, severity or type of infection” (pg. 11, lines 1-3) - no specific details linking the levels of PCT to the extent, severity or type of infection; no evidence for antibiotic agent and/or anti-viral compound treatments; or diagnosing the patient to have a bacterial and/or viral infection;
“The combined measurement of PCT and proADM may, in some embodiments, lead to the decision regarding hospitalization in addition to the antibiotic dose and means of administration to the patient” (pg. 11, lines 3-5) – the specification says “the combined measurement of PCT and proADM”, but not a separate PCT measurement as currently claimed; and “may, in some embodiments, lead to the decision regarding hospitalization in addition to the antibiotic dose” – it may lead to hospitalization, but the antibiotic dose is still outside of the PCT and proADM predictions. Phrase “may lead” is not a definitive disclosure of the invention;
“Elevated PCT levels could identify whether a patient had a bacterial or viral infection” (pg. 34, line 13) – phrase “could” is not a definitive disclosure of the invention.
Finally, claim 23 recites “diagnosing the patient to have a bacterial and/or viral infection”, which can be interpreted as “diagnosing the patient to have a bacterial or viral infection”. However, prior art does not recognize PCT as a biomarker capable of distinguishing bacterial infection from viral.
Kamat et al. (Clin Infect Dis. 2020 Jan 16;70(3):538-542) teach a systematic review and meta-analysis of using procalcitonin to distinguish bacterial pneumonia, from viral pneumonia (Abstract). Kamat concludes that PCT cannot distinguish bacterial from viral CAP infection “The present meta-analysis suggests that, in managing CAP, an infection of broad and diverse etiology, a serum procalcitonin level is unlikely to provide information that will enable clinicians to immediately address whether the infection is bacterial and antibiotics need to be administered or whether it is viral and antibiotics may be withheld” (pg. 540, col. 2, par. 1). Claim 23 recites diagnosing infection in general terms, and community-acquired pneumonia (CAP) of Kamat does belong to infections.
Neither prior art, no the specification provide evidence for PCT being used for (a) diagnosing the patient to have a bacterial and/or viral infection based on the measured level of PCT or (b) treating said patient with an antibiotic agent and/or anti-viral compound.
Based on the above findings, one of ordinary skill in the art would conclude that Applicant did not have possession of the claimed invention at the time the application was originally filed.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 35 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 35 recites “wherein the at least one clinical score comprises the NEWS score,
preferably a NEWS score of at least one point.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 35 recites the broad recitation of determining the NEWS score, and the claim also recites “preferably a NEWS score of at least one point” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 23, 35, 36, and 39 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature or a naturally occurring correlation, i.e., a correlation between a level of MR-proADM and a prognosis of disease progression without significantly more.
Claims 23, 35, 36, and 39 are directed to a process, which is one of the four statutory categories.
Claim 23 recites determining a level of MR-proADM in patients 18 years or older, having a qSOFA score of 0 or 1, showing no clinical symptoms of a blood stream infection, a sepsis, a severe sepsis, and/or septic shock, not hospitalized, and the sample is obtained prior to clinical assessment in a hospital of said suspected respiratory infection, and is not diagnosed with a blood stream infection, a sepsis, a severe sepsis and/or septic shock, and admitting the patient having a determined MR-proADM level between 1.2 to 1.45 nmol/l to hospital.
The method is directed to establishing a relationship between a level of MR-proADM and a medical need for admitting the patient to hospital, which is categorized as a naturally occurring correlation, and therefore it is a judicial exception.
The claim also recites determining a level of procalcitonin (PCT) or fragment(s) thereof to be above 0.25 ng/ml. This additional step is directed to establishing a relationship between a level of PCT and diagnosing the patient to have a bacterial and/or viral infection, which is also categorized as a naturally occurring correlation, and therefore it is a judicial exception.
Claim 23 recites additional elements of preparing a sample from a patient, determining a level of MR-proADM, and determining a level of PCT. The additional elements of “preparing” and “determining” is an insignificant extra-solution activity that amounts to mere data gathering necessary to apply the judicial exception.
The naturally occurring correlation of claim 23 is only generally linked to a prognosis of disease progression and a need for hospitalization. The claim does not recite any specific steps or treatments the patient should receive after admission to hospital based on recited MR-proADM levels.
The additional step of “diagnosing” amounts to making a conclusion based on the results of PCT level measurement. The step of “diagnosing” is a mental process, performed in the human mind, since diagnosing is considered an observation, evaluation, and/or a judgement. The limitation of “diagnosing” falls into the mental process groupings of abstract ideas and therefore is a judicial exception.
The claim also recites treating the diagnosed patient with an antibiotic agent and/or anti-viral compound. Although the additional step of treating the patient indicates that a treatment is to be administered, it does not provide any specific information as to how the patient is to be treated. Since the patient is already suspected of having a respiratory infection, reciting treating the patient with an antibiotic agent and/or anti-viral compound covers any possible medication treatment that a doctor can administer to the patient having a respiratory infection. The claim does not limit the doctor from using any possible treatment options for a patient who is already suspected of having a respiratory infection. Therefore, the limitation of treating thus fails to meaningfully limit the claim because it does not require any particular medication or treatment, and is at best the equivalent of merely adding the words “apply it” to the judicial exception.
Accordingly, the limitation of treating does not integrate the recited judicial exception into a practical application and the claims are therefore directed to the judicial exception.
Claim 23 as a whole does not amount to significantly more than the judicial exception of a law of nature or a naturally occurring correlation. The concept of measuring MR-proADM level in blood samples of patients with infections and sepsis as a marker of mortality risk and severity is well-understood, routine, and convention (for examples, see Cicuendez et al. (IDS; Intensive Care Medicine Experimental, 2015) and Guignant et al. (IDS; Intensive Care Med. 2009)). Measuring PCT level also known in the art - Stalenhoef et al. (Journal of Infection, May 2018, 77, pp. 18–24) teach determining levels of PCT and MR-proADM biomarkers for assessment of disease severity and treatment decisions in community acquired febrile urinary tract infections (Summary and Fig. 2b).
Similarly, claims 35, 36, and 39, which are dependent from claim 23, are rejected as failing to recite significantly more than the judicial exception of an abstract idea since each claim specifies decision steps that do not further integrate a law of nature or a naturally occurring correlation into a practical application.
Therefore, claims 23, 35, 36, and 39 are ineligible under 35 U.S.C. 101.
Response to Arguments
Applicant's arguments filed April 13, 2026 have been fully considered.
Claims 23 and 34-39 were rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement.
Applicant requests reconsideration (pg. 5, par. 1) and specifically argues that “Applicant does not make the argument, and the claim does not require, that only patients with a determined MR-proADM level between 1.2 to 1.45 nmol/1 require hospital treatment, rather, that patients with a determined MR-proADM level between 1.2 to 1.45 nmol/l do require hospital treatment” (pg. 5, last par. – pg. 6, par. 1).
The argument is persuasive and the rejection of claims 23, 35, 36, and 39 under 35 U.S.C. § 112(a) is withdrawn as it relates to MR-proADM level between 1.2 to 1.45 nmol/l.
Claims 23 and 34-39 were rejected under 35 U.S.C. § 112(b).
Applicant argues that “claim 23 is amended to delete reference to a cut-off level of 1.2 nmol/1 and the phrase "comparing said determined level to the cut-off level." Thus, claim 23 recites a single range of values for MR-proADM and is clear” (pg. 6, par. 4). The argument is persuasive and the rejection claims 23, 36, and 39 under 35 U.S.C. § 112(b) is withdrawn.
Applicant argues that “claim 35 is amended to recite "wherein the at least one clinical score comprises the NEWS score, preferably a NEWS score of at least one point."” (pg. 7, par. 2). The argument is persuasive and the previous rejection of claim 35 is withdrawn. However, the use of “preferably” in the claim necessitates another 112(b) rejection (see above for details).
Claims 23 and 34-39 were rejected under 35 U.S.C. § 101.
Applicant argues that “claim 23 is amended to include determining a PCT level in the patient above 0.25 ng/ml, diagnosing the patient as having a bacterial and/or viral infection based on this level, and treating the patient with an antibiotic agent and/or anti-viral compound based on the diagnosis/level of PCT” (pg. 7, par. 5) and “As amended, any judicial exception present in claim 23 is integrated into a practical application, namely effecting a particular treatment or prophylaxis for a disease or medical condition” (pg. 7, par. 5). The argument is not persuasive because additional measurement of PCT biomarker does not provide for “a particular treatment or prophylaxis for a disease or medical condition” and does not limit the doctor from using any possible treatment options for a patient who is already suspected of having a respiratory infection (see above for details).
Additionally, measuring PCT levels for diagnosing and treating patients is not supported by the specification. Therefore, claims 23, 35, 36, and 39 are rejected under 35 U.S.C. § 112(a).
Subject Matter Free of the Prior Art
Claims 23, 35, 36, and 39 are free of the prior art.
The prior art neither teaches nor suggests a method comprising determining a level of MR-proADM in the sample and admitting the patient having a determined MR-proADM level between 1.2 and 1.45 nmol/l in said sample to hospital; and determining a level of PCT for diagnosing and treatment purposes.
The closest prior art of Albrich et al. (BMC Infectious Diseases, 2011, 11:112) teaches a cut-off MR-proADM level of 1.5 nmol/l for admission to hospital.
Conclusion
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 date of this final action.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677
Prosecution Insights