DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis 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.
Claim Status
Claims 1, 7, 9-12, 15-18, 20-21, 30-34, 36, 45, and 48 are pending.
Claims 2-6, 8, 13-14, 19, 22-29, 35, 37-44, 46-47, and 49-241 are canceled.
Claims 1, 7, 9-12, 15-18, 20-21, 30-34, 36, 45, and 48 are under examination.
Claims 1, 7, 9-12, 15-18, 20-21, 30-34, 36, 45, and 48 are rejected.
Priority
Applicant's claim for the benefit of a prior-filed application, PCT/US2020/054033, filed 10/20/2020, is acknowledged, which claims domestic benefit to US provisional application 62/909,530, filed on 10/02/2019, and claims domestic benefit to US provisional application 63/009,331, filed on 04/03/2020
Accordingly, each of claims 1, 7, 9-12, 15-18, 20-21, 30-34, 36, 45, and 48 are afforded the effective filing date of 10/02/2019.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 05/25/2022 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
Drawings
The Drawings submitted 04/01/2022 are accepted.
Nucleotide and/or Amino Acid Sequence Disclosures
The sequence listing submitted 04/01/2022 has been accepted.
Specification
The disclosure is objected to for the following informalities. It is noted that for purposes of the instant Office Action, any reference to the specification pertains to the clean copy of the substitute specification as originally filed on 04/01/2022.
Hyperlinks
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Non-limiting examples include the reference section item 36-37, 50, 52, and 53. Applicant will note that this is exemplary and other instances may exist. It is requested that all instances be corrected.
Abstract
The abstract of the disclosure is objected to because it is presented on two pages, which include text other than the abstract. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Appropriate correction for all objections to the specification is required.
Claim Rejections - 35 USC § 112
35 U.S.C. 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1, 7, 9-12, 15-18, 20-21, 30-34, 36, 45, and 48 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites “obtaining or having obtained quantitative data”. The limitation “having obtained” doesn’t recite any active steps and it's not clear what the scope of the limitations are. For compact prosecution the active step of obtaining will be examined. Claim(s) 7, 9-12, 15-18, 20-21, 30-34, 36, 45, and 48 is/are rejected for the same reason because they depend from claim 1, and does not resolve the indefiniteness issue in those claims.
Claim 21 recites “administering or having administered therapy to the subject based on the therapy recommendation”. The limitation “having administered therapy” doesn’t recite any active steps and it's not clear what the scope of the limitations are. For compact prosecution the active step of administering will be examined.
Claim 31 recites “the classification-specific score for the subject using the first subscore and the second subscore”. It is unclear how the two subscores are used to obtain the classification-specific score. Claim(s) 32 is/are rejected for the same reason because they depend from claims 31, respectively, and do not resolve the indefiniteness issue in those claims.
Claim 34 recites “wherein the machine-learned model is a support vector machine (SVM), that receives, as input, one or more classification-specific scores and outputs the classification of the subject”. It is unclear whether the wherein clause is intended to require the inputting and outputting steps are within the metes and bounds of the claimed invention, or if it is only further limiting the SVM such that the inputting and outputting is not required within the metes and bounds of the invention. The rejection may be overcome by clarifying what steps are required to be performed.
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, 7, 9-12, 15-18, 20-21, 30-34, 36, 45, and 48 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to method, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claim 1:
determining a classification of a subject based on the quantitative data using a patient subtype classifier.
Dependent claim 7:
identifying a therapy recommendation for the subject based at least in part on the classification.
Dependent claim 30:
determining, for at least one candidate classification of the subject, a classification- specific score for the subject;
determining, by the patient subtype classifier, based on the classification-specific score, the classification of the subject.
Dependent claim 31:
determining a first subscore of the quantitative data for the subject for one or more biomarkers of the candidate classification, wherein the quantitative data for the subject for the one or more biomarkers of the candidate classification are increased relative to the quantitative data for the one or more biomarkers for one or more control subjects;
determining a second subscore of the quantitative expression for the subject for one or more additional biomarkers of the candidate classification, wherein the quantitative data for the subject for the one or more additional biomarkers of the candidate classification are decreased relative to the quantitative data for the one or more additional biomarkers for the one or more control subjects; and
determining the classification-specific score for the subject using the first subscore and the second subscore.
Dependent claims 9-12, 15-18, 20, 32-34, 36, 45, and 48 recite further steps that limit the judicial exceptions in independent claim 1 and, as such, also are directed to those abstract ideas. For example, claim 9 further limits host response of claim 1, claims 10-11 further limit the classification of claim 1, claims 12, 15-16, and 18 further limit responsive to the classification of claims 10 and 11, claim 17 further limits the therapy recommendation of claim 16, claim 20 further limits the therapy of claim 18, claim 32 further limits the subscore of claim 31, claim 33 further limits the patient subtype of claim 1, claim 34 further limits machine learning model of claim 33, claim 45 further limits the therapy of claim 7, and claim 48 further limits the subtype of claim 45.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually determine and identify. Without further detail as to the methodology involved in “determining a classification of a subject “, “identifying a therapy recommendation”, “determining, for at least one candidate classification of the subject, a classification- specific score”, “determining, by the patient subtype classifier”, “determining a first subscore”, “determining a second subscore”, and “determining the classification-specific score”; under the BRI, one may simply, for example, use pen and paper to recommending a therapy for a dysregulated host response.
Therefore, claim 1 and those claims dependent therefrom recite an abstract idea and a law of nature/natural phenomenon [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claim 1:
obtaining or having obtained quantitative data for at least a first biomarker, a second biomarker, and a third biomarker wherein the first biomarker is one of STOM, MME, BNT3A2, HLA-DPA1, ZNF831, or CD3G, wherein the second biomarker is one of EPB42, GSPT1, LAT, HK3, or SERPINB 1, and wherein the third biomarker is one of SLC1A5, IGF2BP2, ANXA3, GBP2, TNFRSF1, BTN3A2, OR TNFRSF1A; and determining a classification of a subject based on the quantitative data using a patient subtype classifier.
Dependent claim 21:
administering or having administered therapy to the subject based on the therapy recommendation.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “obtaining”, perform function of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
With respect to claim 21, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to administering or having administered therapy do not impose any meaningful limitations on the abstract idea, or on how the abstract idea is performed. These steps are insignificant extra-solution activity to the judicial exception (MPEP 2106.05(g)(2)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)).
As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claim 21 and those claims dependent therefrom, those steps directed to administering or having administered therapy are not directed to a particular treatment in accordance with MPEP 2106.04(d)(2). In order for a limitation to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception.
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A. Claim(s) 1, 7, 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Spencer et al, (US 2017/009297 A 1 (SPENCER PHILLIPPA MARIA [GB] ET AL) published 12 January 2017, cited on IDS dated 05/25/2022) in view of Toufiq et al. (Toufiq, Mohammed, et al. "Annexin A3 in sepsis: novel perspectives from an exploration of public. "Immunology 155.1 (2018): 18-23, newly cited).
Claim 1 is directed to A method for determining a patient subtype for a subject exhibiting a dysregulated host response, the method comprising: obtaining or having obtained quantitative data for at least a first biomarker, a second biomarker, and a third biomarker wherein the first biomarker is one of STOM, MME, BNT3A2, HLA-DPA1, ZNF831, or CD3G, wherein the second biomarker is one of EPB42, GSPT1, LAT, HK3, or SERPINB 1, and wherein the third biomarker is one of SLC1A5, IGF2BP2, ANXA3, GBP2, TNFRSF1, BTN3A2, OR TNFRSF1A; and determining a classification of a subject based on the quantitative data using a patient subtype classifier.
Spencer discloses classifying biological samples using a biomarker signature (list of 266 biomarkers, Table 1) to pre-symptomatically predict/detect the development and a biomarker signature that could differentiate between sepsis and systematic inflammatory response syndrome (SIRS) and/or differentiate between sepsis and non-sepsis [0022]. Spencer further discloses within the table biomarkers HLA-DPA1 and HK3 but is silent on biomarkers SLC1A5, IGF2BP2, ANXA3, GBP2, TNFRSF1, BTN3A2, OR TNFRSF1A.
However, Toufiq discloses Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data [title]. Toufiq further discloses the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis [summary]. Toufiq also discloses ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes [summary].
Claim 7 is directed to the method of claim 1, further comprising identifying a therapy recommendation for the subject based at least in part on the classification.
Spencer discloses the output from the analytical process may enable the time to onset of symptoms to be predicted, such as 1, 2, or 3 days prior to onset of symptoms, and consequently may be particularly valuable and useful to a medical practitioner in Suggesting a course of treatment, especially when the choice of course of treatment is dependent on the progression of the disease [0049].
Claim 9 is directed to the method of claim 1, wherein the dysregulated host response of the subject comprises one of sepsis and dysregulated host response not caused by infection.
Spencer discloses methods for classifying biological samples using a biomarker signature (list of 266 biomarkers, Table 1) to pre-symptomatically predict/detect the development and a biomarker signature that could differentiate between sepsis and systematic inflammatory response syndrome (SIRS) and/or differentiate between sepsis and non-sepsis [0022].
Claim 10 is directed to the method of any one of claims1, wherein the classification of the subject comprises one of subtype A or subtype B.
Spencer discloses the machine learning output the predictive accuracy of the selected biomarker signature and also indicate whether the specific patient data set is indicative of the development of sepsis, versus non-sepsis and/or SIRS [0027] which reads on classifying the subject into at least two subtypes.
Claim 11 is directed to the method of any one of claims1, wherein the classification of the subject comprises one of subtype A, subtype B, or subtype C.
Spencer discloses the machine learning output the predictive accuracy of the selected biomarker signature and also indicate whether the specific patient data set is indicative of the development of sepsis, versus non-sepsis and/or SIRS [0027], which reads on three different subtypes.
In regards to claim(s) 1, 7, 9, and 11 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 Spencer with Toufiq as they both disclose biomarkers for sepsis analysis. The motivation would have been to combine the biomarkers of Toufiq with the biomarkers of Spencer as they all are known biomarkers for sepsis. All the claimed biomarkers were known, in the art and one skilled in the art could have combined the biomarkers as claimed by known methods.
B. Claims 12, 15-18, 20-21, 30-34, 36, 45, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Spencer in view of Toufiq, as applied to claims 1, 7, and 9 as above, and in further view of Wong et al (Wong, Hector R., et al. "Developing a clinically feasible personalized medicine approach to pediatric septic shock." American journal of respiratory and critical care medicine 191.3 (2015): 309-315, newly cited).
Claim 12 is directed to the method of claim 10 wherein responsive to the classification of the subject comprising subtype A, the therapy recommendation identified for the subject comprises at least no immunosuppressive therapy, no corticosteroid therapy, or no hydrocortisone.
Spencer discloses the ability to detect the earliest signs of infection and/or sepsis has clear benefits in terms of allowing treatment as soon as possible. Indications of the severity of the condition and likely out [0020]. Spencer and Toufiq are silent on the therapy recommendation identified for the subject comprises at least no immunosuppressive therapy, no corticosteroid therapy, or no hydrocortisone.
However, Wong discloses developing a clinically feasible personalized medicine approach to pediatric septic shock [title]. Wong further discloses accordingly, the subclassification method has the potential to promote personalized medicine in that allocation to subclass A or B could potentially direct therapy [p. 312, col. 2, par. 2]. Wong also discloses the subclassification method identifies a group of patients (subclass A) who may not respond favorably to adjunctive corticosteroids [p. 312, col. 2, par. 2].
Claim 15 is directed to the method of claim 10, wherein responsive to the classification of the subject comprising subtype B, the therapy recommendation identified for the subject comprises at least one of no therapy recommendation, immune stimulation therapy, suppression of immune regulation therapy, blocking of immune suppression therapy, blocking of complement activity therapy, and anti-inflammatory therapy.
Spencer discloses the ability to detect the earliest signs of infection and/or sepsis has clear benefits in terms of allowing treatment as soon as possible. Indications of the severity of the condition and likely out [0020]. Spencer and Toufiq are silent on the therapy recommendation.
However, Wong discloses accordingly, the subclassification method has the potential to promote personalized medicine in that allocation to subclass A or B could potentially direct therapy [p. 312, col. 2, par. 2]. Wong also discloses the subclassification method identifies a group of patients (subclass A) who may not respond favorably to adjunctive corticosteroids [p. 312, col. 2, par. 2]. There was no therapy recommendation for subclass B.
Claim 16 is directed to the method of claim 10, wherein responsive to the classification of the subject comprising subtype B, the therapy recommendation identified for the subject further comprises at least one of a checkpoint inhibitor, a blocker of complement components, a blocker of complement component receptors, and a blocker of a pro-inflammatory cytokine.
The limitation of claim 16 is considered disclosed as only one limitation is required to be performed per the claimed “or” statement in claim 15. As the prior art discloses no therapy recommendation, further limiting steps of claim 16 are not required to be performed as it is conditional.
Claim 17 is directed to the method of claim 16, wherein the therapy recommendation identified for the subject further comprises at least one of GM-CSF, anti-PD-1, anti-PD-L1, anti- CLTA-4, anti-CEACAM-1, anti-TIM-3, anti-BTLA, IL-7, INEF-gamma, IFN-beta ia regulator, IL-22 agonist, IFN-alpha regulator, IFN-lambda regulator, IFN-alpha 2b stimulant, anti-C5a, anti-C3a, anti-C5aR, anti-C3aR, anti-TNF-alpha, and anti-IL-6, Anti-HMGB1, ST2 antibody, IL- 33 antibody.
The limitation of claim 17 is considered disclosed as only one limitation is required to be performed per the claimed “or” statement in claim 15. As the prior art discloses no therapy recommendation, further limiting steps of claim 17 are not required to be performed as it is conditional.
Claim 18 is directed to the method of claim 11, wherein responsive to the classification of the subject comprising subtype C, the therapy recommendation identified for the subject comprises at least one of no therapy recommendation, immune stimulation therapy, suppression of immune regulation therapy, blocking of immune suppression therapy, modulators of coagulation therapy, and modulators of vascular permeability therapy, checkpoint inhibitor, and anticoagulant.
Spencer discloses the ability to detect the earliest signs of infection and/or sepsis has clear benefits in terms of allowing treatment as soon as possible. Spencer further discloses indications of the severity of the condition and likely outcomes [0020]. Spencer and Toufiq are silent on the therapy recommendation.
However, Wong discloses a total of 57 subjects (34%) were allocated to subclass A, and 111 subjects were allocated to subclass B with no subjects were allocated to subclass C [p. 311, col, 2, par. 3]. As there were no subjects allocated there was also no therapy recommendation for this subclass.
Claim 20 is directed to the method of claim 18, wherein the therapy recommendation identified for the subject further comprises at least one of GM-CSF, anti-PD-1, anti-PD-L1, anti-CLTA-4, anti-CEACAM-1, anti-TIM-3, anti-BTLA, IL-7, INF-gamma, IFN- beta la regulator, IL-22 agonist, IFN-alpha regulator, IFN-lambda regulator, IFN-alpha 2b stimulant, activated protein C, antithrombin, and thrombomodulin.
The limitation of claim 20 is considered disclosed as only one limitation is required to be performed per the claimed “or” statement in claim 18. As the prior art discloses no therapy recommendation, further limiting steps of claim 20 are not required to be performed as it is conditional.
Claim 21 is directed to the method of claim 7, further comprising administering or having administered therapy to the subject based on the therapy recommendation.
Spencer and Toufiq are silent on administering or having administered therapy.
Spencer discloses the ability to detect the earliest signs of infection and/or sepsis has clear benefits in terms of allowing treatment as soon as possible. Indications of the severity of the condition and likely out [0020]. Spencer and Toufiq are silent on the administering a therapy recommendation.
However, Wong discloses accordingly, the subclassification method has the potential to promote personalized medicine in that allocation to subclass A or B could potentially direct therapy [p. 312, col. 2, par. 2]. Wong also discloses the subclassification method identifies a group of patients (subclass A) who may not respond favorably to adjunctive corticosteroids [p. 312, col. 2, par. 2]. It would be obvious to one in the art that giving a corticosteroid can be administered as a therapy.
Claim 30 is directed to the method of claim 1, wherein the classification of the subject is determined by: determining, for at least one candidate classification of the subject, a classification- specific score for the subject; determining, by the patient subtype classifier, based on the classification-specific score, the classification of the subject.
Spencer discloses the method preferably uses mathematical model ling tools and/or algorithms to monitor and assess expression of the biomarkers both qualitatively and quantitatively [0047]. Spencer further discloses the tools could in particular include Support vector machine (SVM) algorithms, decision trees, random forests, artificial neural net [0047] which reads on a patient subtype classifier. Spencer and Toufiq are silent on classification- specific score for the subject.
However, Wong discloses Gene expression mosaics representing the expression patterns of the 100 subclass defining genes were generated using the Gene Expression Dynamics Inspector [p. 310, col. 3, par. 3]. Wong further discloses the gene expression mosaics from individual patients were compared with subclass reference mosaics using a public analysis platform. Wong also discloses the absolute difference in RGB pixel-to pixel intensity was calculated for each individual patient mosaic, relative to the reference mosaics [p. 311, col. 1, par. 1]. Wong further discloses 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 [p. 311, col. 1, par. 1] which reads on determining, by the patient subtype classifier, based on the classification-specific score. Wong further discloses as an alternative to subclassification based on gene expression mosaics and computer assisted image analysis, we constructed a Gene Expression Score to allocate subjects into subclass A or B [p. 311, col. 3, par. 3].
Claim 31 is directed to the method of claim 30, wherein determining the classification-specific score comprises: determining a first subscore of the quantitative data for the subject for one or more biomarkers of the candidate classification, wherein the quantitative data for the subject for the one or more biomarkers of the candidate classification are increased relative to the quantitative data for the one or more biomarkers for one or more control subjects; determining a second subscore of the quantitative expression for the subject for one or more additional biomarkers of the candidate classification, wherein the quantitative data for the subject for the one or more additional biomarkers of the candidate classification are decreased relative to the quantitative data for the one or more additional biomarkers for the one or more control subjects; and determining the classification-specific score for the subject using the first subscore and the second subscore.
Spencer discloses the method preferably uses mathematical model ling tools and/or algorithms to monitor and assess expression of the biomarkers both qualitatively and quantitatively [0047]. Spencer further discloses the tools could in particular include Support vector machine (SVM) algorithms, decision trees, random forests, artificial neural net [0047] which reads on a patient subtype classifier. Spencer and Toufiq are silent on classification- specific score for the subject.
However, Wong discloses Gene expression mosaics representing the expression patterns of the 100 subclass defining genes were generated using the Gene Expression Dynamics Inspector [p. 310, col. 3, par. 3]. Wong further discloses the gene expression mosaics from individual patients were compared with subclass reference mosaics using a public analysis platform. Wong also discloses the absolute difference in RGB pixel-to pixel intensity was calculated for each individual patient mosaic, relative to the reference mosaics [p. 311, col. 1, par. 1]. Wong further discloses 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 [p. 311, col. 1, par. 1].
Claim 32 is directed to the method of claim 31, wherein one or both of the first subscore and the second subscore are geometric means.
Spencer and Toufiq are silent on a subscore.
However, Wong discloses GES was defined to quantify the range of variability in expression of the 100 subclass defining genes by calculating the sum of the squared differences between the expression levels of each gene and the geometric mean of all genes [p. 311, col. 1, par. 2].
Claim 33 is directed to the method of claim 1, wherein the patient subtype classifier is a machine-learned model.
Spencer discloses the method preferably uses mathematical model ling tools and/or algorithms to monitor and assess expression of the biomarkers both qualitatively and quantitatively [0047]. Spencer further discloses the tools could in particular include Support vector machine (SVM) algorithms, decision trees, random forests, artificial neural net [0047] which reads on a patient subtype classifier as a machine learning model.
Claim 34 is directed to the method of claim 33, wherein the machine-learned model is a support vector machine (SVM), that receives, as input, one or more classification-specific scores and outputs the classification of the subject.
Spencer discloses the method preferably uses mathematical model ling tools and/or algorithms to monitor and assess expression of the biomarkers both qualitatively and quantitatively [0047]. Spencer further discloses the tools could in particular include Support vector machine (SVM) algorithms, decision trees, random forests, artificial neural net [0047] which reads on a patient subtype classifier as a machine learning model. Spencer also discloses a patient data set, for example that comprising gene expression levels for the 266 biomarkers in a patient blood sample, is inputted into the ANN, having selected a biomarker signature (list of biomarkers), and will thereby output the predictive accuracy, of the selected biomarker set is indicative of the development of sepsis, versus non sepsis and/or SIRS. [0027] which reads on a core contributing to the output of a subtype.
Claim 36 is directed to the method of claim 30,wherein the patient subtype classifier determines the classification of the subject by: comparing the classification-specific scores to one or more threshold values; and determining the classification of the subject based on the comparisons.
Spencer and Toufiq are silent on classification- specific score for the subject.
However, Wong discloses Gene expression mosaics representing the expression patterns of the 100 subclass defining genes were generated using the Gene Expression Dynamics Inspector [p. 310, col. 3, par. 3]. Wong discloses 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 [p. 311, col. 1, par. 1].
Claim 45 is directed to the method of claim 7, wherein: the therapy recommendation identified for the subject further comprises corticosteroid therapy, no corticosteroid therapy, or no therapy recommendation.
Spencer and Toufiq are silent on the therapy recommendation identified for the subject comprises at least no immunosuppressive therapy, no corticosteroid therapy, or no hydrocortisone.
However, Wong discloses developing a clinically feasible personalized medicine approach to pediatric septic shock [title]. Wong further discloses accordingly, the subclassification method has the potential to promote personalized medicine in that allocation to subclass A or B could potentially direct therapy [p. 312, col. 2, par. 2]. Wong also discloses the subclassification method identifies a group of patients (subclass A) who may not respond favorably to adjunctive corticosteroids [p. 312, col. 2, par. 2] which reads on a therapy recommendation of no corticosteroid for group A.
Claim 48 is directed to the method of claim 45, wherein the subtype is subtype A or subtype C.
Spencer and Toufiq are silent on the therapy recommendation identified for the subject comprises at least no immunosuppressive therapy, no corticosteroid therapy, or no hydrocortisone.
However, Wong discloses developing a clinically feasible personalized medicine approach to pediatric septic shock [title]. Wong further discloses accordingly, the subclassification method has the potential to promote personalized medicine in that allocation to subclass A or B could potentially direct therapy [p. 312, col. 2, par. 2]. Wong also discloses the subclassification method identifies a group of patients (subclass A) who may not respond favorably to adjunctive corticosteroids [p. 312, col. 2, par. 2] which reads on a therapy recommendation of no corticosteroid for group A.
In regards to claim(s) 12, 15-18, 20-21, 30-34, 36, 45, and 48, 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 Spencer and Toufiq with Wong as they are all directed to analyzing sepsis through biomarkers. The motivation would have been to combine the classifying methods of Spencer with the therapy recommendation of Wong to immuneenhancing therapies to improve sepsis outcomes as disclosed by Wong [p. 314, col, 3, par. 2].
Conclusion
No claims are allowed.
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/D.M.B./Examiner, Art Unit 1685
/Soren Harward/Primary Examiner, TC 1600