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 .
Claim Status
Claims 1-6, 8-9, 12, 14-20, 24-25, and 29-30 are pending and being examined on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color (Figure 1A and 1B). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The disclosure is objected to because of the following informalities: in paragraph [0022], the figures are described based on color (“where red intensity correlates with increased gene expression and blue intensity correlates with decreased gene expression”). Unless a petition has been filed to include color drawings, the drawings will be presented in grayscale. Descriptions should not use color to describe the figures.
Appropriate correction is required.
Claim Objections
Claims 9, 14-16, 25, and 29 are objected to because of the following informalities:
Claim 9 reads “the presence or absence or chronic disease” and should read “the presence or absence [[or]]of chronic disease”.
Claim 14 reads “further comprising administering a treatment comprising one or more corticosteroid to a patient that is not high risk, or administering a treatment comprising one or more therapy excluding a corticosteroid to a patient that is classified as high risk, to provide a method of treating a pediatric patient with septic shock” and should read “further comprising administering a treatment comprising one or more corticosteroids to a patient that is not high risk, or administering a treatment comprising one or more [[therapy]]therapies excluding a corticosteroid to a patient that is classified as high risk, to provide a method of treating a pediatric patient with septic shock”.
Claim 15 reads “wherein one or more high risk therapy is administered to a patient classified as high risk” and should read “wherein one or more high risk [[therapy is]]therapies are administered to a patient classified as high risk”.
Claim 16 reads “wherein the one or more high risk therapy comprises” and should read “wherein the one or more high risk [[therapy comprises]]therapies comprise”.
Claim 25 reads “wherein a patient classified as high risk after the second time point is administered one or more high risk therapy, or wherein a patient not classified as high risk after the second time point is administered a treatment comprising one or more corticosteroid” and should read “wherein a patient classified as high risk after the second time point is administered one or more high risk [[therapy]]therapies, or wherein a patient not classified as high risk after the second time point is administered a treatment comprising one or more corticosteroids”.
Claim 29 reads “wherein the patient classified as high risk and administered one or more high risk therapy after the first time point is not classified as high risk after the second time point” and should read “wherein the patient classified as high risk and administered one or more high risk [[therapy]]therapies after the first time point is not classified as high risk after the second time point”.
Appropriate correction is required.
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 1-6, 8-9, 12, and 30 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (e.g.: a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claim(s) is/are directed to a judicial exception encompassing abstract ideas and natural phenomena. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception as set forth below. The judicial exception is not integrated into a practical application of the judicial exception.
The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S., (2010) (slip op., at 5). “Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U. S. 63, 67 (1972).
Additionally, the unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Inti, 134 S. Ct. 2347, 2354 (2014).
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter? Yes - the claims are directed to methods.
Step 2A, prong 1. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes - Where the claims are directed to “classifying” a patient as high risk or other than high risk”, the claims are directed to an abstract idea; it is the mental identification of a phenotype, or the correlation of data and information.
Furthermore, the claims are directed to an asserted correlation between biomarker expression and adverse outcomes in septic shock; such a correlation is a natural phenomenon which is a genotype:phenotype relationship.
Step 2A, prong 2. Does the claim recite additional elements that integrate the judicial exception into a practical application? No - The judicial exception(s) to which the claims are directed are not integrated into a practical application because there are no required particular practical steps recited related to the classification of the patient as high risk of adverse outcomes, such as applying a particular septic shock treatment to the subject.
Step 2B. Does the claim recite additional elements that amount to significantly more than the judicial exception? No - The claims recite only routine steps related to analyzing expression levels of biomarkers.
Additionally, it is noted that the specification indicates that the practical steps of data collection were routinely practiced in the prior art. For example, the specification provides (paragraph [0047]), that the detection of gene expression of the 100 gene biomarker panel has previously been performed to construct patient mosaic gene expression endotypes. Additionally, Wong et al. (2015) teaches the analysis of gene expression and mosaic endotypes using the specific gene panel of 100 biomarkers as listed in claim 1.
So even where a practical step of the claim may require collecting gene expression data using conventional methods that have been practiced in the art, in University of Utah Res. Foundation v. Ambry Genetics Corp. (Fed Cir, 2014), the Court addressed claims that recite known methodological steps for collecting data (specifically genetic information) to be used in the application of a judicial exception, and held that:
Having determined that the comparison steps of claims 7 and 8 are abstract ideas, we move to the second step of Alice and ask whether the particular mechanism for the comparisons added by claims 7 or 8 renders the claims patent-eligible. For this step, Alice dictates that we ask whether the remaining elements, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to “transform the nature of the claim’ into a patent-eligible application.” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297). There must be a further inventive concept to take the claim into the realm of patent-eligibility. Id. at 2355. The second paragraph of claim 7 describes the way in which the sequences are compared: they are compared by 1) hybridizing a BRCA gene probe and 2) detecting the presence of a hybridization product. Similarly, claim 8 requires 1) amplification of the BRCA1 gene and 2) sequencing of the amplified nucleic acids. The non-patent-ineligible elements of claims 7 and 8 do not add “enough” to make the claims as a whole patent- eligible.
Additionally, In University of Utah Research v. Ambry Genetics the courts stated, "Recently in Alice the Supreme Court reiterated its two-step test to determine patent eligibility for any claims that allegedly encompass abstract ideas. First, "we determine whether the claims at issue are directed to [a] patent-ineligible concept. If so, we then ask, ‘what else is there in the claims before us?" Id. at 2355 (quoting Mayo, 132 S. Ct. at 1296-97) (citations and punctuation omitted). That is, we next ask whether the remaining elements, either in isolation or combination with the other non-patent- ineligible elements, are sufficient to " ‘transform the nature of the claim’ into a patent- eligible application." Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further "inventive concept" to take the claim into the realm of patent eligibility."
For these reasons the claims are rejected under 35 USC 101 as directed to subject matter that is not significantly more than a judicial exception.
Claim Rejections - 35 USC § 112b - Indefiniteness
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 1-6, 8-9, 12, 14-20, 24-25, and 29-30 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 1 is directed to a method of classifying “a patient” with septic shock. The claim goes on to specify that the sample used for this classifying is obtained from “a pediatric patient”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “a patient”, and the claim also recites “a pediatric patient” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Furthermore, claim 1 refers to “the patient” in lines 6-7 and 10-11. It is unclear whether “the patient” refers to the genus “patient” or to the specific type of patient “pediatric patient”. For purposes of examination “the patient” will refer back to the generic “a patient with septic shock” in the preamble of the claim. However, further clarification is required.
Claim 1 is indefinite in that the gene expression mosaic is calculated for the patient based on the expression levels of 100 biomarkers (lines 5-6) and then the Z value is calculated using “the gene expression reference mosaic for the patient”. It is unclear if this is the same gene expression mosaic calculated previously in the claim or if this is an entirely new metric. The specification does not provide any clarification. For the purposes of examination, the gene expression reference mosaic for the patient is going to be interpreted as the gene expression mosaic that is calculated based on the gene expression of the 100 biomarkers. However, further clarification is required.
Claims 2-6, 8-9, 12, 14-20, 24-25, and 29-30 depend from claim 1, inherit these deficiencies, and are rejected on the same basis.
Claim 18 is directed to the method of claim 14 “comprising improving an outcome in a pediatric patient with septic shock”. “Improving an outcome” is indefinite in that no reference metric is provided to indicate what “improving” might encompass. It is unclear what the standard outcome is by which an improvement is being made. Therefore, the scope of the claim is indefinite.
Claims 20, 24-25, and 29 depend from claim 18, inherit this deficiency, and are rejected on the same basis.
Claim 20 recites the limitation "the second time point" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims 24-25 and 29 depend from claim 20, inherit this deficiency, and are rejected on the same basis.
Claim 24 recites the limitation "the second time point" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 25 recites the limitation "the second time point" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 29 depends from claim 25, inherits this deficiency, and is rejected on the same basis.
Claim 29 recites the limitation "the second time point" in line 3. There is insufficient antecedent basis for this limitation in the claim.
In regards to the rejection of claims 20, 24, 25, and 29 for including the limitation “the second time point” with a lack of antecedent basis: in the interest of compact prosecution, the second time point is being interpreted as referring to the second time point as defined by claim 19 for purposes of examination.
Claim Rejections - 35 USC § 112d – Failure to Further Limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 18 and 30 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 18 is directed to the method of claim 14, “comprising improving an outcome in a pediatric patient with septic shock”. However, this is inherent to the method of claim 14, in which a treatment is administered to a patient based on the classification of high risk or other than high risk given the teaching of the specification that patients in the high risk subclass do not benefit from being administered corticosteroids. Therefore, claim 18 does not further limit claim 14.
Claim 30 is directed to the method of claim 1, “wherein the patient is a pediatric patient”. However, claim 1 already defines that the patient is “a pediatric patient with septic shock”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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 1-2, 5-6, 8-9, 12, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong 2015 (Wong et al., American journal of respiratory and critical care medicine, 2015; cited on IDS of 10/12/2023, C18).
Claim 1: Wang 2015 teaches classifying a pediatric patient with septic shock into specific endotype groups (A or B), in which endotype A patients had a higher mortality rate and a higher rate of a complicated course than those in endotype B (this reads on high risk of adverse outcome and/or mortality or other than high risk of adverse outcome and/or mortality). Wang 2015 teaches obtaining samples from pediatric patients with septic shock (pg 310, col 3) and analyzing the samples to determine the expression levels of 100 biomarkers to generate a gene expression mosaic for the patient (pg 310, col 3). Wang 2015 teaches determining a Z value for the patient wherein “absolute difference in RGB pixel-to-pixel intensity was calculated for each individual patient mosaic, relative to the reference mosaics” and “Final subclass allocation was based on the least difference between the individual patient mosaic and one of the reference mosaics representing the septic shock subclasses” (which reads on Equation 1). Wang 2015 teaches classifying the patient into one of the septic shock subclasses based on a threshold cutoff value wherein a score lower than the cutoff value was associated with subclass A (high risk) and a score greater than the cutoff value was associated with subclass B (other than high risk; pg 312, col 3). Wang 2015 teaches that the 100 biomarkers comprise all 100 of the listed genes in claim 1 (Supplementary Table 1).
Claim 2: Wong 2015 teaches that the cutoff Z value is determined by modeling an interaction between the Z value (GES score of each subclass) and the receipt of corticosteroids using logistic regression (“We used logistic regression to test the association between adjunctive corticosteroids and outcomes within each subclass”, pg 314, col 1).
Claim 5: Wong 2015 teaches the difference between the gene expression reference mosaic of the patient and the reference mosaic is calculated by a pixel-to-pixel intensity difference (“The absolute difference in RGB pixel-to-pixel intensity was calculated for each individual patient mosaic, relative to the reference mosaics”, pg 311, col 1).
Claim 6: Wong 2015 teaches that the biomarker expression levels are determined by mRNA quantification (“We measured expression of the 100 subclass defining genes using a multiplex messenger RNA (mRNA) quantification platform”, pg 310, col 2).
Claims 8 and 9: Wong 2015 teaches that the classification is combined with one or more patient demographic data and/or other clinical characteristics, specifically age, presence of co-morbidities of the patient, and illness severity (“we used logistic regression to test the association between class allocation and outcome adjusted for age, presence of comorbidity, and illness severity (PRISM scores)” pg 313, col 2-3).
Claim 12: Wong 2015 teaches that samples were obtained within the first 48 hours of presentation with septic shock (“Blood samples were obtained within 24 hours of initial presentation to the PICU with septic shock”, pg 310, col 3).
Claim 30: Wong 2015 teaches that the patient is a pediatric patient (pg 310, col 3).
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.
Claim 4 is rejected under 35 U.S.C. 103 as obvious over Wong 2015 (Wong et al., American journal of respiratory and critical care medicine, 2015; cited on IDS of 10/12/2023, C18).
The teachings of Wong 2015 are detailed in the 102 rejection above. Relevant to the instantly rejected claims, Wong 2015 teaches that the cutoff Z value is determined by modeling an interaction between the Z value (GES score of each subclass) and the receipt of corticosteroids using logistic regression (“We used logistic regression to test the association between adjunctive corticosteroids and outcomes within each subclass”, pg 314, col 1). Wong teaches that this threshold value can delineate between endotypes, and that the cutoff value in their calculations is 401 (pg 312, col 3).
Wong 2015 does not teach that the cutoff value is about 15. However, Wong 2015 teaches that a threshold value based on a specific percentile of calculated endotype category can be successfully used to accurately classify patients. It would have been prima facie obvious to one skilled in the art to apply the same knowledge to the calculated single value for each mosaic, as demonstrated by the GES in Wong 2015. One would be motivated to use a threshold value for classification given the assertion by Wong 2015 that this allows for classification with a high level of sensitivity and specificity (pg 312, col 3). One would have a reasonable expectation of success given that Wong 2015 is also using gene expression mosaics to then calculate a single value (GES), which is used in an algorithm to establish a cutoff for classification.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Wong 2015 (Wong et al., American journal of respiratory and critical care medicine, 2015; cited on IDS of 10/12/2023, C18) as applied to claims 1-2, 5-6, 8-9, 12, and 30 above and further in view of Gauthier (Gauthier et al., Bone Marrow Transplant 2019).
The teachings of Wong 2015 are detailed in the 102 rejection above. Relevant to the instantly rejected claims, Wong 2015 teaches that the cutoff Z value is determined by modeling an interaction between the Z value (GES score of each subclass) and the receipt of corticosteroids using logistic regression (“We used logistic regression to test the association between adjunctive corticosteroids and outcomes within each subclass”, pg 314, col 1).
Wong 2015 does not teach that fitting the Z value using cubic splines. However, using cubic splines to model continuous variables with respect to a clinical outcome is known in the art, as taught by Gauthier.
Gauthier teach using an alternative modeling strategy that enables exploration of non-linear continuous associations between a continuous variable and clinical outcomes, particular cubic splines (pg 676, col 2, paragraph 2).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Wong 2015 with that of Gauthier to fit the Z value using cubic splines. One would be motivated to do so given the assertion by Gauthier that using linear regression to dichotomize or impose a linear relationship between a variable and an outcome “can lead to loss of information” which “might impair the predictive ability of the model” (pg 676, col 1, paragraph 1). One would have a reasonable expectation of success given that Wong 2015 is attempting to use an association between a continuous variable (Z value) and an outcome (high risk of adverse outcome vs other than high risk of adverse outcome) to create a predictive model, which Gauthier teaches cubic splines can be particularly beneficial for constructing (pg 679, col 2, paragraph 3).
Claims 14-20, 24-25, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Wong 2015 (Wong et al., American journal of respiratory and critical care medicine, 2015; cited on IDS of 10/12/2023, C18) as applied to claims 1-2, 5-6, 8-9, 12, and 30 above and further in view of Wong 2019 (US2019/0065666A1; cited on IDS of 10/12/2023, A1).
The teachings of Wong 2015 are detailed in the 102 rejection above. Relevant to the instantly rejected claims, Wong 2015 teaches that patients classified as endotype A (high risk) do not respond favorably to treatment with corticosteroids and exhibit an increased risk of mortality/worse outcome with corticosteroid treatment (pg 314, col 1 and 3).
Though Wong 2015 implies that patients classified as not high risk can receive corticosteroids while those classified as high risk (subclass A) may benefit the most from more high risk therapies such as immune-enhancing therapies (pg 314, col 3), Wong 2015 does not explicitly teach administering a treatment based on the classification of high risk or other than high risk. However, administration of an appropriate treatment following classification of a patient as high risk or other than high risk (endotype A vs endotype B) is known in the art, as taught by Wong 2019.
Wong 2019 teaches a method for classifying pediatric patient with septic shock as high risk (endotype A) or low risk (endotype B), in which two or more biomarkers selected from a 100 gene biomarker list are examined for expression levels (the same 100 biomarkers as taught in the instant application; paragraph [0007] and Table 1).
Claim 14: Wong 2019 teaches “administering a treatment including one or more corticosteroid to a patient that is not endotype A/high risk, or administering a treatment including one or more therapy excluding a corticosteroid to a patient that is classified as endotype A/high risk, to provide a method of treating a pediatric patient with septic shock” (paragraph [0016]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Wong 2015 (who teaches that patients classified as not high risk can receive corticosteroids while those classified as high risk (subclass A) may benefit the most from more high risk therapies such as immune-enhancing therapies) with that of Wong 2019 who teaches administering corticosteroids to those pediatric patients with septic shock not classified as high risk and teaches using therapies without corticosteroids for those with high risk. One would be motivated to administer therapies in this way given the combined teachings of both Wong 2015 and Wong 2019 that patients in the high risk endotype A subclass have a higher incidence of mortality when administered corticosteroids than those in other than endotype A subclass (Wong 2015: pg 314, col 3; Wong 2019: paragraphs [0075-0076]). One would have a reasonable expectation of success given that Wong 2015 and Wong 2019 are using the same gene set to classify pediatric septic shock patients into similar high risk and other than high risk categories.
Claim 15: Wong 2019 teaches “one or more high risk therapy can be administered to a patient classified as endotype A/high risk” (paragraph [0016]).
Claim 16: Wong 2019 teaches “the one or more high risk therapy includes at least one of immune enhancing therapy, extracorporeal membrane oxygenation/life support, plasmapheresis, pulmonary artery catheterization, and/or high volume continuous hemofiltration” (paragraph [0016]).
Claim 17: Wong 2019 teaches “the immune enhancing therapy includes administration of GMCSF, interleukin-7, and/or anti-PD-I” (paragraph [0016]).
Claim 18: Wong 2019 teaches the method of administering an appropriate treatment to a patient includes “improving an outcome in a pediatric patient with septic shock” (paragraph [0016]).
Claim 19: Wong 2019 teaches “obtaining a sample from a patient at a later time point, analyzing the subsequent expression levels of the two or more biomarkers selected from the biomarkers listed in Table 1, and determining whether the expression levels of the two or more biomarkers are non-elected above a cut-off levels, thereby determining if the patient’s endotype classification has changed”. Wong 2019 further teaches “maintaining the treatment being administered if that patient’s endotype classification has not changed, or changing the treatment being administered if the patient’s endotype classification has changed” (paragraph [0017]).
Claims 20 and 24: Wong 2019 teaches that the second time point is on day 3, relative to the first time point on day 1, therefore being in the range of 24 to 96 hours, or longer after the first time point (paragraph [0090]).
Claim 25: Wong 2019 teaches that “Corticosteroids were associated with increased risk of mortality among subjects who persisted as endotype A” (paragraph [0090]). While Wong 2019 does not explicitly teach administering another treatment after the second time point, it would be obvious to those skilled in the art that those classified as endotype A after the second time point should not be administered corticosteroids, in accordance with the findings and teachings regarding classification at the first time point.
Claim 29: Wong 2019 does not explicitly teach an instance in which a patient classified as high risk and administered a high risk therapy after the first time point is not classified as high risk after the second time point. However, Wong 2019 teaches administering a high risk therapy to a pediatric septic shock patient after classification of high risk at a first time point (paragraph [0016]). Wong 2019 additionally teaches that subjects exhibit transition between endotypes A and B during a 1 to 3 day comparison study (paragraph [0090]). Additionally, Wong 2019 teaches that administration of treatment of a high risk therapy to a patient classified as high risk includes “improving an outcome in a pediatric patient with septic shock” (paragraph [0016]). Therefore, it is an obvious desirable result that following administration of a high risk therapy to a patient after classification at a first time point would lead to the patient not being classified as high risk after the second time point, thus being an indication of an “improved outcome”.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683