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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on October 14, 2025 is acknowledged. The traversal is on the ground(s) that subject matter of all claims is sufficiently related that a thorough search for the subject matter of any one Group of claims would encompass a search for the subject matter of the remaining claims and therefore the search and examination can be made without search burden (Response). This is not found persuasive. As stated in the restriction requirement, Applicants’ product claim is directed to encompass any reagent that is for amplifying a gene which need not necessarily be limited to its particular intent of use (i.e., ascertaining risk of incidence of a healthcare-associated infection in a patient). Therefore, a thorough search of a particular method of use would not reveal the products (i.e., reagents for amplifying the gene TAP2) in context of other physical conditions or means of detections. The Office notes that the restriction mailed on August 14, 2025 offered a rejoinder option under in re Ochiai, where if Applicants opted to elect the product claims, and the product becomes allowable, all withdrawn process of its use would be entitled to rejoinder (so long as the direction to maintained eligibility was followed). Applicants did not elect this option, but chose to elect the particular method of use, and this usage, as discussed above, would not reveal all prior art applicable to the non-elected product as well as requiring considerations under non-prior art issues under 35 U.S.C. 101 and 112(a), where search and examination of both inventions would place an undue burden on the Office.
For these reasons, the requirement is still deemed proper and is therefore made FINAL.
Claim 12 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 14, 2025.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on April 4, 2023 is proper and is being 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.
Claims 3-5 and 13 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.
Claim 3 is indefinite because the claim lacks a conjunction between the last two genes recited in each of the category of genes. For example, for the first category of gene reciting the phrase, “GNLY, S100A9, … OAS2, OAS3”, should have the conjunction “and” between the genes “OAS2” and “OAS3”. For the purpose of prosecution, this assumption has been made.
This correction should be made to all of the categories of the genes recited in claim 3.
Claim 4 is indefinite for missing a conjunction between the genes, “ZAP70” and “HP”. For the purpose of prosecution, the conjunction, “and” has been assumed.
Claim 5 is indefinite for missing a conjunction between the genes, “CD74” and “HP”. For the purpose of prosecution, the conjunction, “and” has been assumed.
Claim 13 is indefinite for reciting the phrase, “using the in vitro or ex vivo: of means for amplifying and/or means for detecting the expression of TAP2 …” because the claim does not have an antecedent basis to refer to the means recited as being “the in vitro or ex vivo”. Also, an embodiment of claim 13 embodies, “[a] method comprising using the in vitro or ex vivo: of means for amplifying …”. It is unclear what is meant by a method using an in vitro or ex vivo of means [or ‘of a kit’]…” For the purpose of prosecution, the phrase has been interpreted to mean that the claims is directed to an in vitro or ex vivo method for determining the risk of incidence of a healthcare associated infection in a patient by: means for amplifying and/or detecting the expression of TAP2; or using a kit of reagents for said amplifying and/or detection means.
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.
Claim 2 is 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. This is a Written Description Rejection.
The Federal Circuit reiterated that mere use of the same words in the specification and the claim (an in ipsis verbis test) is not sufficient to establish written description.
The written description requirement ensures that, “an applicant invented the subject matter which is claimed. Further, the written description requirement for a claimed genus may be satisfied through a sufficient description of a representative number of species by 1) reduction to practice; 2) reduction to drawing; or 3) disclosure of relevant identifying characteristics (i.e., structure of other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure) (MPEP 2163 at II(A)(3)(a)(ii)).
Reduction to Practice
The specification discloses that TAP2 at its mRNA expression level is seen to be correlated with a healthcare-associated infection when examined at various stages after the being administered care.
“TAP2 gene have been associated with certain diseases, such as ankylosing spondylitis. The expression of the transcript of this gene has also been studied in septic patients, in whom it has been shown that it made it possible to identify patients with a particular endotype associated with the occurrence of death at 28 days” (page 2)
“It has now been discovered, entirely surprisingly, that measuring the expression of the TAP2 gene made it possible to determine the risk of incidence of a healthcare-associated infection in a patient.” (page 2-3)
“A reduction in the expression of TAP2 at the mRNA level, measured on D5/7 from inclusion in the cohort, was associated with a greater risk of incidence of a healthcare-associated infection before D30 in the overall patient population … This association was always significant after adjustment with the SOFA and Charlson score” (page 80)
“The prediction models also showed that the expression of TAP2 at the mRNA level made it possible to predict the incidence of a healthcare-associated infection in the 4 days or 7 days following the sample being taken” (page 81)
“Thus, the results obtained show that the measurement of the expression of TAP2 alone makes it possible to predict the incidence of healthcare-associated infection(s) in the 15 days starting from the immunoinflammatory attack, in the 4 days following the sample being taken or in the 7 days following the sample being taken” (page 82)
The specification also claims that the examination of at least one additional gene expression level along with TAP2 expression aids in enhanced determination.
“the expression level of TAP2 and also that of other genes was measured by RT-qPCR … measurement of the expression of one of more of these other genes, in addition to the measurement of the expression of TAP2, makes it possible to improve the performance (compared to the measurement of the expression of TAP2 alone) in predicting the risk of incidence of a healthcare-associated infection, whether before D15 starting from inclusion in the cohort (table 6) or in the 4 days or in the 7 days following the sample being taken (table 7)” (page 82)
The specification specifically lists a specific set of genes (as reflected in claim 3) which are categorized as those of: a) innate immune system; b) cell cycle; c) cytokines; d) anti-inflammatory cytokines; e) pro-inflammatory cytokine receptors in region 2q11-2q12; f) all pro-inflammatory cytokines; cytoskeleton formation; g) any and all involved in gene expression and transcription; h) growth factors; i) metabolism; j) adaptive immune system; k)signal transduction; l) modulation of acute phase (see page 7-8).
However, claim 2 essentially encompasses any and all genes of the recited categories as being to be used with the claimed method of determining the risk of incidents of healthcare-associated infection in a patient, when their findings of the additional genes being actually correlated is based on a small subset of each of these categories.
Therefore, the specific set of genes disclosed in the specification is not deemed to be a representative number of species of each category of genes so as to justify the genus as presently claimed in the method of claim 2.
Reduction to Drawing
The specification does not have any figures for demonstrating a reasonable number of species of the genes so as to demonstrate the genus of genes from each categories discussed above.
Disclosure of Relevant Identifying Characteristics
While one could argue that a skilled artisan would be able to identify the “representative number of species” of such genes and their expressions from each of the categories, each of the categories encompasses a tremendously large numbers of species and experimenting each of these genes of the claimed categories along with TAP2 gene expression, and determining whether or not they are useful in the “risk” determination would not satisfy the written description for the genus claims because, “the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art” (MPEP 2163(I)(A)). For the claims at issue, such essential or critical feature is the number of genes of each category which demonstrate a representative number of species therein. Applicants simply have not disclosed enough number of species within the claimed genus as evidenced by the small number of species for each category in the specification, as reflected in claim 3.
As stated in University of California v. Eli Lilly and Co. at page 1404:
An adequate written description of a DNA ... "requires a precise definition, such as by structure, formula, chemical name, or physical properties," not a mere wish or plan for obtaining the claimed chemical invention. Fiers v. Revel, 984 F.2d 1164, 1171, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). Accordingly, "an adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself." Id. at 1170, 25 USPQ2d at 1606.
Therefore, for the foregoing reasons, the genus embraced by the claims is not sufficiently described by the number of species disclosed in the specification, and therefore, the specification lacks written description 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 1-11 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the law of nature (i.e., judicial exception) without significantly more. The claims recite the correlation that exists between the level of TAP2 gene and combination of TAP2 gene and an additional gene from a category of genes (recited in claim 2) and a patient’s propensity to develop infection from healthcare visit. This judicial exception is not integrated into a practical application because the claims do not integrate this judicial exception into a practical application because reciting general means of detection that are either generic or conventionally employed are deemed to be insignificant extra-solution activity.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. Claims 1-11 and 13 satisfy the present inquiry as being drawn to a method.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Prong-1 inquiry under step 2A determines whether the claim(s) recites an abstract idea, a law of nature, or a natural phenomenon.
The specification discloses the natural correlation that exist between the level of TAP2 gene and a subject’s risk in developing healthcare-associated infection:
“It has now been discovered, entirely surprisingly, that measuring the expression of the TAP2 gene made it possible to determine the risk of incidence of a healthcare-associated infection in a patient. This has never been shown or suggested in the literature. Patients having a high risk of contracting a care-associated infection could advantageously benefit from customized treatment (page 2-3)
“A reduction in the expression of TAP2 at the mRNA level, measured on D5/7 from inclusion in the cohort, was associated with a greater risk of incidence of a healthcare-associated infection before D30 in the overall patient population … This association was always significant after adjustment with the SOFA and Charlson score” (page 80)
Moreover, the prediction models showed that the expression of TAP2 at the mRNA level, measured on D3/4 or D5/7 from inclusion in the cohort, made it possible to predict the incidence of a healthcare-associated infection before D15 from inclusion in the cohort (page 81)
The prediction models also showed that the expression of TAP2 at the mRNA level made it possible to predict the incidence of a healthcare-associated infection in the 4 days or 7 days following the sample being taken (page 81)
Thus, the results obtained show that the measurement of the expression of TAP2 alone makes it possible to predict the incidence of healthcare-associated infection(s) in the 15 days starting from the immunoinflammatory attack, in the 4 days following the sample being taken or in the 7 days following the sample being taken (page 82)
“the expression level of TAP2 and also that of other genes was measured by RT-qPCR … measurement of the expression of one of more of these other genes, in addition to the measurement of the expression of TAP2, makes it possible to improve the performance (compared to the measurement of the expression of TAP2 alone) in predicting the risk of incidence of a healthcare-associated infection, whether before D15 starting from inclusion in the cohort (table 6) or in the 4 days or in the 7 days following the sample being taken (table 7)” (page 82)
Therefore, the claims recite a judicial exception of a correlation that exists between TAP2 gene and additional gene(s) and a subject’s risk of developing an infection after receiving healthcare treatment. Therefore, claim recites a judicial exception.
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
Claim 1 does not recite any additional meaningful limit to the judicial exception as discussed above.
Claims 2-5 recite at least one additional gene(s) to be used in conjunction with TAP2 gene, but as discussed above, the combination of their genes and their expression is also tied to the natural correlation of the patient’s risk of developing healthcare-associated infection and therefore, do not recite any additional meaningful limit.
Claims 6 and 7 further recite the type of sample form which the genes are examined and the gene expression being measured at mRNA level. However, the gene expression at the mRNA level represents the above-discussed natural correlation; and the sample from which the mRNAs are examined is also based on natural correlation as the natural correlation exists from mRNA that are present in the isolated sample.
Claims 8-10 and 13 recite additional elements directed to the mean of determining the gene expression level, such as RT-PCR, sequencing, hybridization, and utilizing “amplification means”.
However, these means are recited in a highly generic manner and tantamount to “applying” the judicial exception without a meaningful limitation.
As to the use of a housekeeping gene expression level to normalize the expression of TAP2 and at least one additional genes, the use of a housekeeping gene is also recited in a highly generic manner and that which is employed when ascertaining gene expression levels of genes.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
As discussed above, claims 1-7 do not recite any additional elements other that that which are representation of the judicial exception.
The additional elements recited in claims 8-11 and 13 discussed further add more than the judicial exception because the assays such as RT-PCR, hybridization, and sequencing as well as utilizing the expression of housekeeping genes in an expression determination assay, are routinely and conventionally employed in the area of molecular diagnostics.
Therefore, these elements are not deemed significantly more than inclusion of that are commonly used, routine and conventional.
Therefore, the present claims lack patent eligibility.
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.
Claims 1-4, 6-8, 10, 11, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Scicluna et al. (WO 2018/146162 A1, published August 2018; IDS reference).
The present rejection is based on the claim interpretation that the method only requires the measurement of expression of TAP2 in a biological sample from a patient because the intent of the method of “determining the risk of incidence of a healthcare-associated infection” is not actively recited in the steps of the method.
A rejection directed to an alternative claim interpretation where the determination is made is also made below.
With regard to claim 1, Scicluna et al. teach a method of measuring the expression of TAP2 in a biological sample of a patient (“[m]ethod of determining the survival of a patient admitted to an intensive care unit … determining the expression level of at least … TAP2 in a biological sample of said patient”, see claim 1).
With regard claims 2-4, BPGM expression is also measured (“determining the expression level of at least BPGM and/or TAP2 in a biological sample of said patient”, see claim 1).
With regard to claim 6, the biological sample is blood sample (“wherein said biological sample contains white blood cells”, see claim 1).
With regard to claims 7-8, 10, and 13, the means of detection is directed to RT-PCR (thus targets mRNA and based on amplification), microarray analysis (thus hybridization):
“the step of determining the expression level comprises the use of at least one techniques selected from the group consisting of: i. PCR-based methods, preferably RT-PCR, Quantitative RT-PCR, nucleic acid microarray analysis … in situ hybridization …” (page 5, lines 26-29)
With regard toc claim 11, Scicluna et al. teach a well-known means of normalizing the expression levels with an expression level of a housekeeping gene:
“method further comprises the step of normalizing at least one of the determined gene expression levels … Normalization can be carried out against an endogenous unregulated reference gene transcript … These unregulated genes are termed housekeeping genes” (page 19, line 31 to page 20, line 6)
Therefore, the invention as claimed is anticipated by Scicluna et al.
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 to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-4, 6-11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Scicluna et al. (WO 2018/146162, published August 2018; IDS reference) in view of Jain, Mukesh (Briefings in Functional Genomics, 2011, vol. 11, no. 1, pages 63-70).
With regard to claim 1, Scicluna et al. performed genome-wide blood gene expression in blood of adult patients admitted to the ICUs and of patients with sepsis caused by CAP 1admitted to 29 ICUs (see page 1, bottom paragraph).
From the study, the artisans reached a, “consensus in portioning at four molecular endotypes … designed Mars 1-4 … In so doing, we identified 140 genes that clearly stratified Mars1 and Mars4 endotypes” (page 2, lines 1-4).
Scicluna et al. teach that patients classified to Mars1 had the worst outcome with 39% mortality at 28-days as well as the worst outcome until 1 year of patient follow up (page 2, lines 10-12), wherein TAP2 and BPGM as being directed to Mars1 sepsis endotype (“8 genes were derived as candidate biomarker for the identification of sepsis endotypes at ICU admission, with BPGM and TAP2 transcripts delineating the poor prognosis Mars1 sepsis endotype”, page 4, lines 9-11), wherein Mars1 was characterized by “decreased expression in genes that function in both innate and adaptive immune mechanisms” (page 4, lines 21-23) concluding that Mars1 classified patients may represent an “immunoparalyzed” endotype with poor prognosis (see page 4, lines 25-26).
Scicluna et al., teach that these findings are applied in a method of determining the risk of a patients’ adverse outcome due to sepsis (“expression levels of the genes BPGM and TAP2 as prognostic biomarker for a high risk mortality sepsis endotype”, page 1, first paragraph), wherein the determining involves a method analyzing the expression level of, inter alia, the genes TAP2 and/or BPGM from blood a patient (claim 6), wherein the expression is measured at mRNA level (claim 7) involving assays such as RT-PCR (claims 8 and 13), involving hybridization (claim 10), involving normalization with housekeeping gene(s) (claim 11):
“determining the expression level of at least BPGM and/or TAP2 in a biological sample of said patient” (claim 1)
“wherein said biological sample contains white blood cells” (claim 1).
“the step of determining the expression level comprises the use of at least one techniques selected from the group consisting of: i. PCR-based methods, preferably RT-PCR, Quantitative RT-PCR, nucleic acid microarray analysis … in situ hybridization …” (page 5, lines 26-29)
“method further comprises the step of normalizing at least one of the determined gene expression levels … Normalization can be carried out against an endogenous unregulated reference gene transcript … These unregulated genes are termed housekeeping genes” (page 19, line 31 to page 20, line 6)
While Scicluna et al. teach that the TAP2 and/or BPGM gene levels are prognostic markers for determining a patient’s risk of mortality sepsis endotype, the artisans do not explicitly state that the method is for determining the risk of incidents of a healthcare associated infection (claim 1, in-part).
Scicluna et al. do not explicitly teach that a way for measuring a gene expression level is by sequencing (claim 9).
Jain teaches well-known technological advancements which have been available before the effective filing date of the claimed invention wherein sequencing reaction can also be employed to analyze gene expression levels from samples:
“The unprecedented level of sensitivity and high-throughput nature make NGS technologies as the method of choice for gene expression analysis … absolute measurement of gene-expression using RNA-seq provides greater quantitative and qualitative insight, and accuracy than microarray” (page 63)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Scicluna et al. and Jain, thereby arriving at the invention as claimed for the following reasons.
As to the use of an alternatively and conventionally known means of determining the gene expression levels of TAP2 and/or BPGM, such as sequencing means, doing so would have been an obvious application of routinely employed means that yield no more than a predictable outcome based on the knowledge and advantages of utilizing a sequencing means to determine gene expression levels, as discussed by Jain.
As expressed by the Supreme Court, a combination of teachings that add no more than a predictable outcome is likely to be obvious.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
As to utilizing the findings of Scicluna et al. for determining a subject’s risk of developing healthcare associated infection, arriving at such an application would have been obvious based on the findings provided by Scicluna et al. who teach that the genes categorized under Mars1 exhibit lower expression levels and are associated with, “function in both innate and adaptive immune mechanisms”, wherein Mars1 classified patients may represent an “immunoparalyzed” endotype with poor prognosis (see page 4, lines 21-26).
Given that the genes TAPS2 and BGPM are categorized under Mars1 that represent patients with immunoparalysis, and adverse sepsis (inflammatory reaction to infection) outcome, assaying for these genes and their levels would have been an obvious application for the purpose of determining the risk of the patient for developing healthcare-associated infection.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Scicluna et al. (WO 2018/146162, published August 2018; IDS reference) in view of Jain, Mukesh (Briefings in Functional Genomics, 2011, vol. 11, no. 1, pages 63-70), as applied to claims 1-4, 6-11, and 13 above, and further in view of Friggeri et al. (Critical Care, 2016, vol. 20, pages 1-13).
The teachings of Scicluna et al. and Jain have already been discussed above.
While Scicluna et al. explicitly teach assaying for gene expression profiles for identifying genes which are prognosticative for a patient’s risk of developing sepsis after a healthcare treatment, wherein the artisans teach various Mars categories of genes that relate to cytokine signaling, cell growth/proliferation/mobility, lymphocyte pathways, protein catabolism/translations (see Figure 1.3D, also see page 7), the artisans do not explicitly teach an additional gene recited in claim 5.
Friggeri et al. teach that CXCR1 messenger RNA expression is decreased in patients associated with mortality from septic shock:
“we observed an association between decreased CX3CR1 on monocytes after septic shock and decreased functional response of monocytes ex vivo … This provides a link between decreased CX3CR1 and immune dysfunction after sepsis and suggests that the measure of such a host response messenger RNA (mRNA) marker may be useful in evaluation of injury-induced immune alterations” (page 2, 1st column)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Scicluna et al. and Jain with the teachings of Friggeri et al., thereby arriving at the invention as claimed for the following based on the rationale provided for by the court in In re Kerkhoven:
MPEP 2144.06, in discussing art recognized equivalence for the same purpose, mentions In re Kerkhoven, wherein the court expressed the following:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
The inclusion of additional genes to the TAP2 and BPGM, such as CX3CR1 which have been suggested as being useful as a marker for sepsis based on the similar function (i.e., immune dysfunction)2 would have been expected to provide additional information relating to the outcome of the patient’s outlook from infections.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 December 2, 2025
/YJK/
1 a.k.a. Community Acquired Pneumonia
2 Scicluna et al. also teach that the expression level of TAP2 is indicative of immunoparalysis, see page 4, lines 21-26