DETAILED ACTION
Claims 21-39 are pending.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 01/15/2024, 03/12/2024, 09/13/2024, 05/27/2025, and 06/19/2025 have been considered by the examiner.
Claim Rejections - 35 USC § 112
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.
1. Claims 21-38 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.
The steps of instant claim 21 do not reflect the preamble or intended use of diagnosing tubulointerstitial disorders. It is suggested that the claims be amended to add thereby diagnosing tubulointerstitial disorders.
Therefore, instant claim 21 and its dependent claims are indefinite.
The steps of instant claim 28 do not reflect the preamble or intended use of diagnosing one or more kidney diseases. It is suggested the claims be amended to add thereby diagnosing one or more kidney diseases.
Therefore, instant claim 28 and its dependent claims are indefinite.
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.
2.Claims 21-26 and 28-30. 32-39 are rejected under 35 U.S.C. 101 because the claimed product and method are directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 1
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03.
A. Regarding instant claims 21-26, 28-30, and 32-38, 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 21-26, 38-30, and 32-38.
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, instant claims 21-26, 32-33, and 35-37 are directed to a method that measures sCD14-ST (a protein) and correlating the measurement to tubulointerstitial disorders (Step 1: YES).
Instant claims 28-30, 34, and 38 are directed to a method that measures sCD14-ST (a protein) and correlating the measurement to one or more kidney disease (Step 1: YES).
B. Instant claim 39 recites the use of a sCD14-ST antibody, which is a protein. Because proteins are a composition of matter, the sCD14-ST antibody is a composition of matter, which is a statutory category of invention. As explained in the MPEP, it is not necessary to identify single category into which a claim falls, so long as it is clear that the claim falls into at least one category. MPEP 2106.03(I). Here, because the antibody for sCD14-ST is a composition of matter, the claim is to at least one category of invention (Step 1: YES).
Step 2A, Prong 1: Does the claim recite a judicial exception?
This part of the eligibility analysis evaluates whether the claim recites a judicial
exception. As explained in MPEP 2106.04(II) and the October 2019 Update, a claim “recites” a
judicial exception when the judicial exception is “set forth” or “described” in the claim.
A. Regarding instant claims 21-26, 28-30, and 32-38, Example 43 of the “2019 PEG” shows a similar fact pattern.
Regarding claim 1 in 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, instant claim 21 recites measuring sCD14-ST (protein) and correlating the levels of the protein to tubulointerstitial disorders and thus is considered a law of nature. Further, instant claim 21 recites “optionally dividing the concentration of sCD14-ST by a urinary creatinine value”, which is a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. In addition, this type of arithmetic calculation 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. Further, 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. Consequently, instant claim 21 is recite the judicial exception of applying and using a law of nature and an abstract idea.
Instant claim 28 recites measuring sCD14-ST (protein) and correlating the levels of the protein to one or more kidney diseases and thus is considered a law of nature. Further, claim 28 recites “optionally dividing the concentration of sCD14-ST by a urinary creatinine value”, which is a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. In addition, this type of arithmetic calculation 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. Further, 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. Consequently, instant claim 28 is recite the judicial exception of applying and using a law of nature and an abstract idea.
B. Regarding instant claim 39, Example 44 of the “2019 PEG” shows a similar fact
pattern. Claim 1 in example 44 is drawn to denveric acid. The markedly different characteristics
analysis is used to determine if the nature-based product limitation is a product of nature
exception. MPEP 2106.04(c)(I). Although the claim also recites a non-nature based product
limitation (the container), the markedly different characteristics analysis should be applied only
to the nature- based product limitation. MPEP 2106.04(c)(I)(A). The markedly different
characteristics analysis is performed by comparing the nature-based product limitation in the
claim to its naturally occurring counterpart to determine if it has markedly different characteristics from the counterpart. MPEP 2106.04(c)(II). Here, the closest natural counterpart
is naturally occurring denveric acid. When the claimed denveric acid is compared to this
counterpart, the comparison indicates that there are no differences in structure, function, or
other characteristics. Therefore, the claimed denveric acid is a product of nature exception.
Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 576, 589-90 (2013)
(naturally occurring things are “products of nature” which cannot be patented).”
Similarly, instant claim 39 recites the use of a sCD14-ST antibody. The closest natural counterpart to a sCD14-ST antibody is a naturally occurring sCD14-ST antibody. When the claimed markers are compared to this counterpart, the comparison indicates that there are no differences in structure, function, or other characteristics. Further, instant claim 39 recites “dividing the concentration…”, which is a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. In addition, this type of arithmetic calculation 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. Further, 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.
Accordingly, instant claim 39 recites a judicial exception (a product of nature and an
abstract idea), and the analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
A. Regarding instant claims 21-26, 28-30, and 32-38, Example 43 of “2019 PEG” shows a similar fact pattern.
In 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, the 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, instant claims 21 and 28 do not have additional elements that would integrate the judicial exception cited above into a practical application. In comparison to claim 1, Example 43 did not pass step 2A prong 2 with a step of general treatment. Instant claims 21 and 28 don’t even recite a treatment step. Example 43 failed with a step of a general treatment, instant claims 21 and 28 do not recite a further active step, let alone a treatment.
Instant claims 26, 30, and 35 recite “determining” that the subject has tubulointerstitial disorder or one or more kidney disease when the measurements are above a certain threshold, which is directed towards an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing or looking at collected information, which is an act of evaluating information that can be practically performed in the human mind. Instant claim 36 explicitly recites “comparing said ratio…” which is directed towards an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing or looking at collected information, which is an act of evaluating information that can be practically performed in the human mind. Instant claims 37-38 recite “a method of judging…” which is directed towards an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing or looking at collected information, which is an act of evaluating information that can be practically performed in the human mind.
Further, instant claims 33-34 recite the use of a “treatment wherein said treatment is chosen from lifestyle improvement, dietary therapy, drug therapy, immunosuppressive treatment, and kidney transplant” which amounts to nothing more than identifying a correlation and then “applying a treatment” since the treatment step is recited at a high level of generality.
Therefore, instant claims 21-26, 28-30, and 32-38 do not integrate the judicial exception into a practical application.
B. Regarding instant claim 39, Example 44 of the “2019 PEG” shows a similar fact
pattern. In claim 1 of example 44 of the “2019 PEG” and per Step2A, Prong two, the 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. 2019 PEG Section III(A)(2), 84 Fed. Reg. at 54-55. Claim 1 recites an additional
element (the container). Although this limitation indicates that the denveric acid is held in the
container, it does not provide any information as to how the denveric acid is contained, or what
the container is, but instead covers any possible container that a doctor or pharmacist decides
to use. Because denveric acid must be placed in a container in order to store and use it, merely
reciting a generic “container” thus fails to meaningfully limit the claim because it is at best the
equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, the container does not integrate the recited judicial exception into a practical application and the
claim is therefore directed to the judicial exception (Step 2A: YES)”.
While example 44 recites a container which was still not deemed sufficient, instant claim 39 does not recite any container and contains no more than the sCD14-ST antibody (the natural product) and instructions. Example 44 did not pass Step 2A prong 2 with an additional element (the container). Accordingly, instant claim 39 does not have additional elements that would integrate the judicial exception cited above into a practical application.
Therefore, instant claim 39 does not integrate the judicial exception into a practical application.
Step 2B: Does the claim recite significantly more?
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, instant claim 21 recites the additional limitation of “obtaining or having obtained a urinary sample from a subject; contacting said sample with an antibody; detecting sCD 14-ST in said sample by binding of said antibody to sCD 14-ST in said sample”, which recite contacting the naturally occurring proteins, which are merely instructions of obtaining a judicial exception and cannot be considered an inventive concept (STEP 2B: NO).
Instant claim 28 recites the additional limitation of “contacting a sample from said subject with an antibody; detecting sCD 14-ST in said sample by binding of said antibody to sCD 14-ST in said sample” which recite contacting the naturally occurring proteins, which are merely instructions of obtaining a judicial exception and cannot be considered an inventive concept (STEP 2B: NO).
B. Regarding instant claim 39, 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 discussed with respect to Step 2A Prong Two, the claims do not even
recite a container or any additional elements. (Step 2B: NO). The claims are not eligible.
Thus, claims 21-26 and 28-30. 32-39 are rejected under 35 USC 101.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
3.Claims 21-22, 24-26, 28-30, 32, 35, and 37-39 are rejected under 35 U.S.C. 103 as being unpatentable over Carpio et al., “Utility of presepsin (sCD14-ST) as a diagnostic and prognostic marker of sepsis in the emergency department” Clinica Chimica Acta vol. 450, 169-175. 23 Oct. 2015, https://doi.org/10.1016/j.cca.2015.08.013, in view of Kobayashi et al., “Prediction of presepsin concentrations through commensurate decline in kidney function in the elderly.” Clinica chimica acta; international journal of clinical chemistry vol. 500 (2020): 1-9. doi:10.1016/j.cca.2019.09.012 (IDS filed on 01/15/2024).
Instant claim 21 recites “A method of detecting a tubulointerstitial disorder in a subject comprising: obtaining or having obtained a urinary sample from a subject; contacting said sample with an antibody; detecting sCD14-ST in said sample by binding of said antibody to sCD14-ST in said sample; measuring a concentration of sCD14-ST in said sample by immunoassay; and optionally dividing the concentration of sCD14-ST by a urinary creatinine value.”
Instant claim 28 recites “A method of detecting one or more kidney disease in a subject comprising: contacting a sample from said subject with an antibody; detecting sCD14-ST in said sample by binding of said antibody to sCD14-ST in said sample; measuring a concentration of sCD14-ST in said sample by immunoassay; and optionally dividing the concentration of sCD14-ST by a urinary creatinine value.”
Carpio teaches measuring sCD15-ST (also known as presepsin/PSEP) in individuals with kidney disease (see whole document, see page 171 “The patients with a medical history of kidney disease revealed noticeably higher PSEP concentrations”) comprising:
tubulointerstitial disorder detecting sCD14-ST in a sample by binding of said antibody to sCD14-ST in said sample (see page 169 “A chemiluminescent immunoassay using a specific antibody to determine sCD14-ST, named PSEP, is commercially available.”, see page 170 “PSEP was determined using PATHFAST PSEP (LSI Medience Corporation, Tokyo, Japan), a chemiluminescent enzyme immunoassay for the quantitative measurement of PSEP concentration in whole blood or plasma. The test principle is based on the non-competitive chemiluminescence enzyme immunoassay (CLEIA) combined with *MAGTRATIONⓇ technology”);
measuring sCD14-ST in a sample by immunoassay (see page 169 “A chemiluminescent immunoassay using a specific antibody to determine sCD14-ST, named PSEP, is commercially available.”, see page 170 “PSEP was determined using PATHFAST PSEP (LSI Medience Corporation, Tokyo, Japan), a chemiluminescent enzyme immunoassay for the quantitative measurement of PSEP concentration in whole blood or plasma. The test principle is based on the non-competitive chemiluminescence enzyme immunoassay (CLEIA) combined with *MAGTRATIONⓇ technology”) (instant claims 21 and 28). Carpio teaches the subject being suspected of having kidney disease (see page 174) (instant claim 24). Carpio teaches measuring presepsin at least two or more different timing intervals (see page 174 “PSEP values measured at presentation, at 8, 24 and 72 h after admission were statistically evaluated to investigate the ability to determine the efficacy of initial therapeutic measures at a very early stage”) (instant claim 32). Carpio teaches a kit comprising an antibody for sCD14-ST; standard data for correlating a concentration of sCD14-ST, and a degree or renal damage (see page 169 “A chemiluminescent immunoassay using a specific antibody to determine sCD14-ST, named PSEP, is commercially available.”, see page 174 “The noticeably higher PSEP values in patients with a history of kidney disease as indicated in Table 3 give reason to assume that PSEP plasma concentration is associated with renal function. PSEP as a 13 kDa protein is filtered by the glomerulus and reabsorbed within proximal tubular cells. Thus, decreasing kidney function should cause accumulation of PSEP in the circulation, resulting in elevated plasma PSEP concentration. Kidney injury and renal dysfunction occur commonly in septic patients.”). While Carpio does not explicitly recite a “kit” or “instructions”, it would have been obvious that the time of the instant application to include instructions on how to use the kit, as including instructions to a testing device is a common practice in the art (instant claim 39). Carpio teaches all the claimed elements used together. The use of a kit is widely known in the art.
While Carpio teaches that presepsin can be detected in urine (see page 174 “These studies should also address the question of acute or chronic renal failure and corresponding PSEP concentrations in urine in different clinical situations. Such studies could additionally evaluate the diagnostic and prognostic validity of PSEP in patients on chronic dialysis.”), Carpio does not explicitly teach using a urine sample.
Carpio does not teach the tubulointerstitial disorder being nephrosclerosis or being chronic, measuring presepsin in a urine sample, and the concentration of sCD14-ST is greater than 312 pg/mL in patients.
Kobayashi teaches measuring presepsin in a urine sample (see page 7 “Furthermore,
we examined the presepsin concentrations in urine samples among those subjects. The urinary excretion of presepsin increased, inversely proportional to the decline of GFR (data not shown).”) (instant claims 21, 28, and 39). Kobayashi teaches the tubulointerstitial disorder being a chronic condition and the condition being nephrosclerosis (see page 6 “CKD is increasing in incidence and prevalence worldwide, with aging of the global population being the primary factor. CKD affects more than 26 million adults in the United States and about 13 million adults in Japan. Age-related physiological changes such as glomerulosclerosis lead to nephrosclerosis and subsequent nephron loss with normal aging in the elderly.”, see page 8 “The possibility of residual confounding by prevalent CKD due to nephrosclerosis, explaining (at least in part) the association of presepsin concentrations, cannot be excluded”) (instant claims 22, 25, and 29). Kobayashi teaches when the concentration of sCD14-ST is greater than 312 pg/mL in patients with suspected tubulointerstitial disorder and/or kidney disease (see table 6, see page 3 under “3.3. Development and analysis of the prediction equations for presepsin concentrations”) (instant claims 26, 30, and 35). While Kobayashi does not explicitly state judging whether or not to perform a renal biopsy in a subject, where detecting sCD14 occurs before the renal biopsy, Kobayashi teaches the detection of sCD14 in a urine sample (see page 7). It would have been obvious to one of ordinary skill in the art to routinely optimize measuring a non-invasive biomarker test before an invasive renal biopsy (instant claims 37-38).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the teachings of measuring sCD15-ST in a subject who is suspected of having a kidney disease taught by Carpio, with the teachings of measuring presepsin in a urine sample to detect a kidney disease taught by Kobayashi. Kobayashi teaches that presepsin concentrations were exponentially correlated with kidney function decline (see abstract, see page 3). Kobayashi teaches that presepsin concentration in urine samples were increased in those who chronic kidney disease (see page 7). The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
4.Claims 23, 27, 31, and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Carpio and Kobayashi et al., as applied to claims 21-22, 24-26, 28-30, 32, 35, and 37-39 above, in view of Scherberich et al., “Blood monocyte phenotypes and soluble endotoxin receptor CD14 in systemic inflammatory diseases and patients with chronic renal failure.” European Dialysis and Transplant Association - European Renal Association vol. 15,5 (2000): 574-8. doi:10.1093/ndt/15.5.574.
The teachings of Carpio and Kobayashi as it pertains to claims 21-22, 24-26, 28-30, 32, 35, and 37-39 are discussed in the 35 USC 103 rejection above.
Carpio does not teach the tubulointerstitial disorder being tubulointerstitial nephritis.
Scherberich teaches measuring sCD14 in a urine sample to detect tubulointerstitial nephritis (see page 575 under “Soluble CD14 (sCD14)”, see page 577 “In patients with tubulointerstitial nephritis urine levels of sCD14 were significantly higher”) (instant claim 23). Scherberich teaches treating the subject with an immunosuppressive (see page 575 “immunosuppressive drugs down-modulate the CD14 antigen”, see page 576 “Glucocorticoids caused rapid clinical improvement”) (instant claims 27, 31, and 33-34).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the teachings of measuring sCD15-ST in a subject who is suspected of having a kidney disease taught by Carpio, with the teachings of measuring presepsin in a urine sample to detect a kidney disease taught by Kobayashi, and with the teachings of treating tubulointerstitial nephritis with immunosuppressants taught by Scherberich. Scherberich teaches that glucocorticoids caused sCD14 to decrease/down-regulate (see page 576). Scherberich teaches that the release of sCD14 induced a rapid decline of the amount of circulating proinflammatory cells (see page 576). Scherberich further teaches that sCD14 is a promising non-invasive marker to describe enhanced migration of leukocytes into the inflamed kidneys, which occurs in tubulointerstitial nephritis (see page 577). The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
5.Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Carpio and Kobayashi et al., as applied to claims 21-22, 24-26, 28-30, 32, 35, and 37-39 above, in view of Miyoshi et al., “Usefulness of presepsin / creatinine ratio as a new index that corrects for renal function”, The Journal of Medical Investigation, 2021, Volume 68, Issue 1.2, Pages 105-111. https://doi.org/10.2152/jmi.68.105.
The teachings of Carpio and Kobayashi as it pertains to claims 21-22, 24-26, 28-30, 32, 35, and 37-39 are discussed in the 35 USC 103 rejection above.
Carpio does not teach dividing the concentration of sCD14-ST and creatinine to obtain a ratio to diagnose tubulointerstitial disorder.
Kobayashi teaches measuring sCD 14-ST in a urine sample (see page 7 “Furthermore,
we examined the presepsin concentrations in urine samples among those subjects. The urinary excretion of presepsin increased, inversely proportional to the decline of GFR (data not shown).”) and using the measurement to diagnose a tubulointerstitial disorder (see page 6 “CKD is increasing in incidence and prevalence worldwide, with aging of the global population being the primary factor. CKD affects more than 26 million adults in the United States and about 13 million adults in Japan. Age-related physiological changes such as glomerulosclerosis lead to nephrosclerosis and subsequent nephron loss with normal aging in the elderly.”, see page 8 “The possibility of residual confounding by prevalent CKD due to nephrosclerosis, explaining (at least in part) the association of presepsin concentrations, cannot be excluded”) (instant claim 36).
Miyoshi teaches wherein the concentration of sCD 14-ST is divided by creatinine value to obtain a ratio of the amounts of sCD 14-ST and creatinine (see abstract “We evaluated presepsin/creatinine (P-SEP / CRE) and P-SEP / eGFR ratios as possible indices for renal function”); and comparing said ratio to a reference ratio (see page 107 under “stratified comparison of P-SEP/CRE ratio”); the reference ratio is derived from a sample from a subject known not to have exhibited a tubulointerstitial disorder (see figure 4 showing the comparison between a “normal” individual and others who may have a renal disorder), and wherein a ratio of sCD 14-ST to creatinine in the sample from the test subject which is essentially identical to the reference ratio or which is lower than the reference ratio indicates that the subject has not exhibited a renal disorder (see figures 4 and 6) (instant claim 36).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the teachings of measuring sCD14-ST in a subject who is suspected of having a kidney disease taught by Carpio, with the teachings of measuring presepsin in a urine sample to detect a kidney disease taught by Kobayashi, and with the teachings of dividing the amount of sCD14-ST and creatinine to develop a ratio taught by Miyoshi. Miyoshi teaches that the ratio of sCD14-ST (referred to as presepsin or P-SEP) and creatinine is useful as an index that corrects for renal function (see page 105). The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MCKENZIE A DUNN whose telephone number is (571)270-0490. The examiner can normally be reached Monday-Tuesday 730 am -530pm, Wednesday-Friday 730 am-430 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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