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 .
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.
Election/Restrictions
Applicant’s election without traverse of Group II of claims 33-40 in the reply filed on 12/31/2025 is acknowledged.
Claims 21-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/31/2025.
The Applicant was supposed to make an election of species if Group I was elected per the Restriction/Election of 10/31/2025. Because Group I of claims was not elected, no species had to be elected, and they are all withdrawn with their claims without traverse as noted in the reply of 12/31/2025.
Claims 1-20 are cancelled by the Applicant.
Thus, claims 33-40 are under examination.
Priority
This application is a continuation of International Patent Application No. PCT/CN2019/119537 filed on 11/19/2019. Thus, this application claims priority to 11/19/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/18/2022, 07/15/2022, 03/09/2023, 06/12/2025 and 01/22/2026 have been received. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner and all references are considered except where they were lined through.
Claim Objections
Claims 33, 38, and 40 are objected to because of the following informalities:
Regarding claim 33, the claim recites “mixing a sample to be tested, a procalcitonin capture antibody coated on a solid phase, and a soluble CD14 subtype capture antibody coated on a solid phase”. There is no connection between the three parts of the sentence due to the lack of “with”. The Examiner suggests to amend the claim to read as “mixing a sample to be tested with a procalcitonin capture antibody coated on a solid phase, and with a soluble CD14 subtype capture antibody coated on a solid phase”.
Similarly, claims 38 and 40 need to be amended to add the connector “with” so that claim 38 would read “mixing a sample to be tested from the patient with a procalcitonin capture antibody
coated on a solid phase and with a soluble CD14 subtype capture antibody coated on a solid phase”. And claim 40 would read “mixing a sample to be tested from the patient with a procalcitonin capture antibody coated on a solid phase and with a soluble CD14 subtype capture antibody coated on a solid
phase”.
Appropriate correction of claims 33, 38, and 40 is required.
Claim Interpretation
Regarding the term “combined concentration level” of procalcitonin and soluble CD14 subtype, the Examiner is interpreting the term as combined detection of the concentrations of procalcitonin and soluble CD14 subtype and comparing to reference value for each concentration.
Claim Rejections - 35 USC § 112(b)
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.
Claims 33-40 are 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.
Regarding claims 33, the claim recites “adding a detection substrate to the washed complexes to detect the combined concentration level of the procalcitonin and the soluble CD14 subtype in the sample to be tested”. It is not clear how will it be possible to combine the concentrations of procalcitonin (PCT) with soluble CD14 subtype (Presepsin (PSEP)) to result in a combined concentration level because the two biomarkers of procalcitonin and soluble CD14 subtype are measured in different units as noted by Horsch et al. (US 2023/0030564 A1, Fig. 1, “PSEP < or ≥ 1000 pg/ml”, “PCT < or ≥ 2ng/ml”). The specification of the instant case does not define the term combined concentration level and a skilled artisan would not be able to ascertain the meaning of the term from the specification nor from the claims. To move the prosecution, the Examiner is interpreting combined concentration level as combined detection of the concentration levels of procalcitonin and soluble CD14 subtype in the sample to be tested.
Similarly, claim 38 recites “detecting a combined concentration level of the procalcitonin and the soluble CD14 subtype in the sample to be tested”, “comparing the combined concentration level relative to a reference value”, and “identifying the patient having an elevation in the combined concentration level compared to the reference value as suffering from sepsis”. And claim 40 recites “detecting a combined concentration level of the procalcitonin and the soluble CD14 subtype in the sample to be tested”, “comparing the combined concentration level relative to a reference value”, and “evaluating the suspected sepsis patient having an elevation in the combined concentration level compared to the reference value as having higher risk of death”. Both claims 38 and 40 do not provide a definition for the combined concentration of the procalcitonin and the soluble CD14 subtype in the sample to be tested. And as noted above, the specification does not provide a definition for the term combined concentration level nor examples.
Regarding claim 34, the claim recites that “providing the procalcitonin capture antibody and the soluble CD14 subtype capture antibody which are separately coated on the solid phase”. However, claim 35 of the method of claim 33 recites that “the procalcitonin capture antibody
and the soluble CD14 subtype capture antibody are mixed in a range of 5: 1 to 1: 5”. It is not clear how will the two capture antibodies be separately coated if they are mixed as stated by claim 35. The specification does not provide an explanation nor an example on how to separately coat the two antibodies. The specification teaches how to coat a mixture of the two antibodies (Page 26, lines 21-23, “a PCT capture antibody and a Presepsin capture antibody were mixed at a certain ratio, and then the mixture was coated on the surface of a solid phase carrier”).
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 38-40 are rejected under 35 U.S.C. 101 because the claimed invention is for a process or a method that is directed to at least one judicial exception without significantly more. The claims recite a mere collection of information in the form of data that is compared to a cutoff value from which the applicant or doctor will be able to predict the possibility of sepsis in a patient and the risk of death from sepsis. Such an inference is not sufficient to transform the abstract idea of a mental process of a comparison with identification and a law of a nature (correlation of high concentration levels of procalcitonin and soluble CD14 subtype to patient suffering from sepsis or having higher risk of death from sepsis) into a patentable application.
The claims are ineligible because the claims recite at least one judicial exception, i.e., an abstract idea of a mental process (comparing the combined concentration level relative to a reference value)
and a law of nature (correlation of high concentration levels of procalcitonin and soluble CD14 subtype to patient suffering from sepsis or having higher risk of death from sepsis).
Moreover, the claims as a whole do not integrate the judicial exceptions into a practical application nor do they provide an inventive concept. The doctor or skilled artisan is not required to offer any type of treatment or intervention upon the finding of the patient having sepsis or being at risk of death from sepsis.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?)
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03.
Example 43 of “2019 PEG” is particularly enlightening because the fact pattern of claim 1 of example 43 is most similar to the instant application claims.
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 1, the claim is directed to a process, which is one of the statutory categories of invention as the claim recites “A treatment method comprising: (a) calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype; (b) administering a treatment to the patient having a non-responder phenotype.” (Step 1: YES).
Similarly, claims 38 and 40 of the instant application are also directed to a statutory class of a method of identifying a patient as suffering from sepsis or a method of evaluating the prognosis of a suspected sepsis patient respectively that measures the concentrations of procalcitonin and soluble CD14 subtype to compare the combined concentration levels to a reference value for identification and evaluation of sepsis in a patient. (Step 1: YES).
(Step 2A, Prong 1: Does the claim recite an abstract idea, law of nature or natural phenomenon?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 1, the claim recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” and according to broadest reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the ratio of C11 to C13 that can be used to identify whether the patient has the non-respondent phenotype.
Specifically, limitation (a) in claim 1 of Example 43 of the “2019 PEG” recites “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” which has a BRI that requires performing an arithmetic calculation (division) in order to obtain the ratio of C11 to C13 levels, and then using this ratio to identify whether the patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or greater and thus is not responding, or will not respond, to glucocorticoids). This limitation therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be practically performed in the human mind, and is in fact performed in the human mind on a daily basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract ideas.
In addition, limitation (a) describes a naturally occurring relationship between the ratio of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a law of nature. Accordingly, limitation (a) recites a judicial exception (an abstract idea that falls within the mathematical concept and mental process groupings in the “2019 PEG”, and a law of nature), and the analysis must therefore proceed to Step 2A Prong Two.
Similarly, claims 38 and 40 of the instant application recite a judicial exception of an abstract idea of a mental process of comparing the combined concentration level relative to a reference value for identification and evaluation of sepsis in a patient “comparing the combined concentration level relative to a reference value”, an abstract idea of a mental process of identifying a patient with sepsis in claim 38 “identifying the patient having an elevation in the combined concentration level compared to the reference value”, an abstract idea of a mental process of evaluating a patient suspected of having sepsis for risk of death in claim 40 “evaluating the suspected sepsis patient having an elevation in the combined concentration level compared to the reference value”.
Claims 38 and 40 also recite a judicial exception of law of nature of correlating elevated combined concentration levels of procalcitonin and soluble CD14 subtype to having sepsis or being at risk of death from sepsis respectively “identifying the patient having an elevation in the combined concentration level compared to the reference value as suffering from sepsis” and “evaluating the suspected sepsis patient having an elevation in the combined concentration level compared to the reference value as having higher risk of death”.
Last, while example 43 of the “2019 PEG” is drawn to the calculation of a ratio of C11 to C13 levels in limitation (a), claims 38 and 40 of the instant application are just merely detecting the levels of procalcitonin and soluble CD14 subtype and associating the elevated concentration level with the risk of sepsis or the risk of death from sepsis. Thus, claims 38 and 40 of the instant application also describe a naturally occurring relationship between the combined concentration levels of procalcitonin and soluble CD14 subtype and the risk of sepsis or death from sepsis in a patient, and thus is considered to recite a law of nature.
Accordingly, each of claims 38 and 40 of the instant application recites three judicial exceptions of two mental processes and a law of nature, and the analysis must therefore proceed to Step 2A Prong Two.
(Step 2A, Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. Besides the abstract idea, claim 1 of example 43 of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient having a non-responder phenotype”. Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. In fact, this limitation is recited at such a high level of generality that it does not even require a doctor to take the calculation step’s outcome (the patient’s
phenotype) into account when deciding which treatment to administer, making the limitation’s inclusion in this claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception.
Similarly, claims 38 and 40 of the instant application do not have additional elements that would integrate the judicial exceptions cited above into a practical application. The claims have steps of detecting the combined concentration levels of procalcitonin and soluble CD14 subtype to compare to a reference value to identify a patient as suffering from sepsis or being at risk of death from sepsis, and these steps do not integrate the judicial exception into a practical application because they are data gathering steps to use in the detection and comparison, which do not add a meaningful limitation to the method as they are insignificant extra-solution activity. These steps do not integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d). Furthermore, unlike claim 1 of example 43 of the “2019 PEG”, claims 38 and 40 of the instant application do not have a treatment step. In the instant case, the doctor or skilled artisan is not required to perform any action if the patient is identified as suffering from sepsis or being at risk of death from sepsis.
Therefore, claims 38 and 40 do not integrate the judicial exception into a practical application.
(Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2B, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element in limitation (b), which does not require any particular application of the recited calculation and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept (Step 2B: NO). The claim is not eligible.
Similarly, claims 38 and 40 of the instant application simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, such as measuring the concentrations of procalcitonin and soluble CD14 subtype
with a commercially available assay such as chemiluminescent analyzer (Specification, page 28, lines 1-13). Furthermore, the claims themselves are recited at a high level of generality in which any assay can be used as the measurement method for claims 38 and 40.
Thus, claims 38 and 40 are not eligible and are rejected under 35 USC 101.
Regarding claim 38, the claim states the time for performing the detection of procalcitonin and soluble CD14 subtype from a patient who is suspected of suffering from sepsis which does not integrate the judicial exception into a practical application, nor does it amount to significantly more.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 33 -34, 38 and 40 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Horsch et al. (US 2023/0030564 A1, priority to 10/28/2019).
Regarding claim 33, Horsch teaches a method for combined detection of procalcitonin and a soluble CD14 subtype in a sample to be tested (Abstract; [0010], “In particular, the combined determination of Procalcitonin and Presepsin allows for the identification of risk patient”).
Horsch teaches mixing a sample with a procalcitonin capture antibody coated on a solid phase, and with a soluble CD14 subtype capture antibody coated on a solid phase, so that the procalcitonin capture antibody coated on the solid phase binds to the procalcitonin in the sample, and the soluble CD14 subtype capture antibody coated on the solid phase binds to the soluble CD14 subtype in the sample ([0057], [0062]).
Horsch teaches adding a labeled procalcitonin detection antibody and a labeled soluble CD14 subtype detection antibody to the mixture, so that the labeled procalcitonin detection antibody binds to the procalcitonin bound on the procalcitonin capture antibody to form a sandwich complex and the labeled soluble CD14 subtype detection antibody binds to the soluble CD14 subtype bound on the soluble CD14 subtype capture antibody to form a sandwich complex ([0057], [0058], [0062]).
Horsch teaches washing the sandwich complexes to remove unbound substances ([0062]).
Horsch teaches adding a detection substrate to the washed sandwich complexes to detect the combined concentration level of the procalcitonin and the soluble CD14 subtype in the sample ([0062]).
Regarding claim 34, Horsch teaches providing the procalcitonin capture antibody and the soluble CD14 subtype capture antibody which are coated on the solid phase ([0057], [0061]).
Regarding claim 38, Horsch teaches a method of identifying a patient as suffering from sepsis ([0018]; [0121]).
Horsch teaches mixing a sample to be tested from the patient with a procalcitonin capture antibody coated on a solid phase and with a soluble CD14 subtype capture antibody coated on a solid phase ([0057], [0062]).
Horsch teaches adding a labeled procalcitonin detection antibody and a labeled soluble CD14 subtype detection antibody to the mixture ([0057], [0058], [0062]).
Horsch teaches detecting a combined concentration level of the procalcitonin and the soluble CD14 subtype in the sample to be tested ([0062]).
Horsch teaches comparing the combined concentration level relative to a reference value ([0014]; [0094]; [0106]).
Horsch teaches identifying the patient having an elevation in the combined concentration level
compared to the reference value as suffering from sepsis ([0010], “Further, the combined determination of Procalcitonin and Presepsin allows for the identification of patients whose risk for a poor outcome” ;[0283], “patients with a PCT concentration of >2 ng/mL and/or a Presepsin concentration of >1000 pg/mL are at an increased risk of a complicated clinical course.”).
Regarding claim 40, Horsch teaches a method of evaluating the prognosis of a suspected sepsis patient ([0010], “Further, the combined determination of Procalcitonin and Presepsin allows for the identification of patients whose risk for a poor outcome”).
Horsch teaches mixing a sample to be tested from the patient with a procalcitonin capture antibody coated on a solid phase and with a soluble CD14 subtype capture antibody coated on a solid
phase (([0057], [0062]).).
Horsch teaches adding a labeled procalcitonin detection antibody and a labeled soluble CD14
subtype detection antibody to the mixture ([0057], [0058], [0062]).
Horsch teaches detecting a combined concentration level of the procalcitonin and the soluble CD14 subtype in the sample to be tested ([0062]).
Horsch teaches comparing the combined concentration level relative to a reference value (0014]; [0094]; [0106]).
Horsch teaches evaluating the suspected sepsis patient having an elevation in the combined
concentration level compared to the reference value as having higher risk of death (Abstract; [0001]; [0010], “Further, the combined determination of Procalcitonin and Presepsin allows for the identification of patients whose risk for a poor outcome” ;[0283], “patients with a PCT concentration of >2 ng/mL and/or a Presepsin concentration of >1000 pg/mL are at an increased risk of a complicated clinical course.”).
Claim Rejections - 35 USC § 103
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 (PHOSITA) 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.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over Horsch et al. (US 2023/0030564 A1) as applied to claim 38 above, and further in view of Chen et al. (European Journal of Emergency Medicine, 2019, Vol 26 No 5, Accepted 21 May 2018).
Regarding claim 39, Horsch teaches detecting the combined concentration value of the procalcitonin and the soluble CD14 subtype in the sample to be tested from the patient ().
Regarding claim 39, Horsch does not teach detecting the combined concentration levels of procalcitonin and the soluble CD14 subtype in the sample to be tested from the patient within 72 hours after the patient is suspected of suffering from sepsis.
Regarding claim 39, Chen teaches predicting mortality in a patient within 72 hours after the patient is suspected of suffering from sepsis (Abstract, conclusion).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the mortality prediction time frame of Chen with the detection method of Horsch to identify a patient of having sepsis in a timely manner because Chen teaches that the most common preventable medical error leading to unexpected death within 72 hours is inappropriate treatment for sepsis (Page 323, left column, first paragraph). Chen further teaches that early recognition of patients at risk of early mortality is important, as such patients may benefit from aggressive and prompt therapeutic intervention (Page 323, left column, first paragraph). A skilled artisan would have been motivated to combine the above methods to enhance the early identification of sepsis in a patient for treatment purposes. A PHOSITA would have had a reasonable expectation of success in combining the methods of Chane and Horsch based on the methods being in the field of identifying sepsis in a patient. Consequently, it would have been obvious for a PHOSITA to combine the detection timeframe of Chen with the measurements of Horsch to improve the sensitivity of detecting sepsis in a patient for effective treatment.
Conclusion
No claims are allowed.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678