DETAILED ACTION
In application filed on 09/15/2023, Claims 1-29 are pending. The claim set submitted on 04/20/2026 is considered because this is the most recent claim set with some preliminary amendments. Claims 12-23 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/15/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on 04/20/2026 is acknowledged. Claims 1-11 and 24-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/20/2026.
Group II, Claims 12-23 are considered on the merits below.
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 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. All claims are directed to statutory categories, i.e., a method (Claim 23) (Step 1: YES).
Analysis:
Claim 23: Ineligible.
Step 1:
The claim recites a series of steps or acts, including “method for evaluating the development of an infant’s communication ability using the marker set”. Thus, the claim is directed to a process, which is one of the statutory categories of invention (Step 1: YES).
Step 2A, Prong 1:
Claim 23 recites “…the algorithm generating a traumatic brain injury score based on a comparison of the measured expression levels to reference levels…”. Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a math process since claim 23 relates to using a math process to perform the steps reciting the abstract ideas.
Step 2A, Prong Two:
This judicial exception is not integrated into a practical application. In particular, the claim recites ‘additional elements’ which are the steps performed before and after the recited abstract ideas. However, the steps before the abstract ideas are performed in order to gather data necessary to perform the determination step. Thus, these steps do not add a meaningful limitation since these steps are insignificant pre-solution activity.
Once the traumatic brain injury score is generated by the algorithm, no further action takes place. The steps of “measuring expression levels of one or more proteins in the biological sample…”; and “obtaining or having obtained a biological sample” (Claim 12) are recited at a high level of generality that it amounts to mere data gathering (insignificant extra-solution activity). See MPEP 2106.05(g).
Accordingly, these steps are ‘additional elements’ which do not integrate the abstract ideas into a practical application because they do not impose meaningful limits on practicing the abstract ideas (Step 2A, Prong Two: NO).
Step 2B:
Furthermore, the courts have found that limitations adding insignificant extrasolution activity to the judicial exception, such as mere data gathering in conjunction with a law of nature or abstract idea, are limitations found not to be enough to qualify as ‘significantly more’ when recited in a claim with a judicial exception (see the 2014 Interim Guidance on Patent Subject Matter Eligibility of the Federal Register dated December 16, 2014; and MPEP 2106.05(I)(A)). Note that mere data gathering is not significantly more than the abstract idea. See MPEP 2106.05(g).
Claim Objections
Claims 12 is objected to because of the following informalities:
Claim 12 recites “in the same” in line 4 of the Claim. It appears that this limitation should be recited as “in the same biological sample”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 12-17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over by Fernando et al. (Fernando, M. Rohan, et al. "New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes." PloS one 12.8 (2017): e0183915.) in view of Ashley et al. ("Detection of mitochondrial DNA depletion in living human cells using PicoGreen staining." Experimental cell research 303.2 (2005): 432-446., submitted in IDS on 09/15/2023).
Regarding Claim 12, Fernando teaches a method of detecting DNA (See Abstract… Cell-free DNA (cfDNA) in blood) comprising:
obtaining or having obtained a biological sample (See Abstract…Plasma was obtained; See Page 2… Blood samples were obtained from …donors).
staining extracellular vesicles in the same DNA staining dye (See Abstract…A large proportion of extracellular vesicles isolated from plasma were identified as exosomes using a fluorescence probe specific for exosomes and three protein markers, Hsp70, CD9 and CD63, that are commonly used to identify exosome fraction; See Page 5… Qubit™ ds DNA HS assay kit and Qubit™ 3.0 fluorometer was used to quantify DNA isolated from cell-free plasma and plasma exosomes following manufacturer’s recommended protocol. Qubit™ RNA HS assay kit and Qubit™ 3.0 fluorometer was used to quantify RNA isolated from exosomes; Fernando does not teach using mitochondrial DNA specific primers.
Further, Fernando teaches that extracellular vesicles released by cells are classified by their intracellular origin. The three main categories of vesicles are apoptotic bodies, microvesicles and exosomes (Introduction, Page 2).
The limitation “detecting the presence of mitochondrial DNA in the biological sample by monitoring and quantification of extracellular vesicles sizes, extracellular vesicles surface features and content, or extracellular vesicles sizes specific markers” is viewed as optional and thus not required by the claim.
Fernando does not teach “detecting the presence of mitochondrial DNA in the biological sample by staining extracellular vesicles in the same with a DNA staining dye, without using mitochondrial DNA specific primers”.
In the analogous art of the detection of mitochondrial dna depletion in living human cells using picogreen staining, Ashley teaches that “detecting the presence of mitochondrial DNA in the biological sample by staining (See Fig. 1…PicoGreen specifically stains mtDNA and not mtRNA in cells; Under BRI, Examiner submits that virtually all human cells produce and release extracellular vesicles (EVs)) in the same with a DNA staining dye (See Results, Page 435…We found that human mtDNA could be visualised in nonpermeabilised cells with PicoGreen by simply incubating cells for periods of up to 2 h in medium containing the diluted dye.), without using mitochondrial DNA specific primers” (See Page 434…. Single-colour molecular beacon PCR reactions were used to quantify mtDNA levels relative to nuclear DNA; 250 nM each of either mitochondrial or nuclear primers, 100 nM of the corresponding nuclear or mitochondrial probe and 8 ng of target DNA, thereby teaching that the nuclear primer is used while the use of the mitochondrial primer is optional. thereby teaching “without using mitochondrial DNA specific primers”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando to include “detecting the presence of mitochondrial DNA in the biological sample by staining extracellular vesicles in the same with a DNA staining dye, without using mitochondrial DNA specific primers”, as taught by Ashley for the benefit of using PicoGreen to estimate the degree of mtDNA depletion within living cells (Ashley, Abstract), allowing for the development of a simple yet effective method to visualise mtDNA in situ within living cells using the fluorescent stain (Ashley, Abstract).
Regarding Claim 13, the method of claim 12 is obvious over Fernando in view of Ashley. Fernando further teaches the DNA staining dye is selected from at least one of GeiRed, 10 EvaGreen, SYBR, PicoGreen and derivatives, TOTO, YOYO, 8080, POPO, JOJO, LOLO, SYTOX, POPRO, 80-PRO, YO-PRO, TO-PRO, JO-PRO, PO-PRO, LO- PRO, and combinations thereof (See Page 6… Exosomes isolated using Invitrogen Total Exosome isolation (from plasma) method were stained with Quant-iT™ PicoGreen1 fluorescence dye and examined under confocal microscope. “Fig 2A” shows confocal microscopic image of exosomes with intense green fluorescence indicating the presence of dsDNA in exosomes).
Regarding Claim 14, the method of claim 12 is obvious over Fernando in view of Ashley.
Fernando teaches that extracellular vesicles released by cells are classified by their intracellular origin. The three main categories of vesicles are apoptotic bodies, microvesicles and exosomes (Introduction, Page 2).
Fernando does not explicitly teach that the DNA staining dyes is engineered for recognition and quantification of mitochondrial DNA encapsulated within extracellular vesicles.
In the analogous art of the detection of mitochondrial dna depletion in living human cells using picogreen staining, Ashley teaches that “the DNA staining dyes (‘PicoGreen’) is engineered for recognition and quantification of mitochondrial DNA encapsulated within extracellular vesicles” (See Abstract… Quantitative analysis shows that PicoGreen can be used to estimate the degree of mtDNA depletion within living cell; See Page 433…PicoGreen is a fluorescent DNA-specific dye primarily used for quantification of double-stranded DNA in solution [23] and has previously been used to visualize mtDNA in permeabilised cells; Under BRI, Examiner submits that virtually all human cells produce and release extracellular vesicles (EVs)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando to include “the DNA staining dyes is engineered for recognition and quantification of mitochondrial DNA encapsulated within extracellular vesicles”, as taught by Ashley for the benefit of using PicoGreen to estimate the degree of mtDNA depletion within living cells (Ashley, Abstract), allowing for the development of a simple yet effective method to visualise mtDNA in situ within living cells using the fluorescent stain (Ashley, Abstract).
Regarding Claim 15, the method of claim 12 is obvious over Fernando in view of Ashley.
Fernando teaches that the biological sample is a liquid biopsy, or is an exhaled breath condensate (See Abstract…Plasma was obtained; See Page 2… Blood samples were obtained from …donors, thereby teaching “liquid biopsy”).
Regarding Claim 16, the method of claim 12 is obvious over Fernando in view of Ashley.
Fernando teaches that DNA is circulating cell-free DNA, or DNA encapsulated in extracellular vesicles (See Abstract… Cell-free DNA (cfDNA) in blood is used as a source of genetic material for noninvasive prenatal and cancer diagnostic assays in clinical practice; See Page 2…In this exosome characterization study, we found evidence that more than 90% of cfDNA in human blood plasma is localized in plasma exosomes, thereby teaching “circulating cell-free DNA”).
Regarding Claim 17, the method of claim 12 is obvious over Fernando in view of Ashley.
Fernando teaches that a DNA sample is obtained and tested in an emergency room, a critical care setting, an ICU, a sideline, a locker room, or a battlefield, in a point of care diagnostic, or an at-home test (See Page 2… Blood samples were obtained from the American Red Cross Apheresis Center located at the University of Nebraska Medical Center).
Regarding Claim 20, the method of claim 12 is obvious over Fernando in view of Ashley.
Fernando teach the detection of DNA ((See Abstract… Cell-free DNA (cfDNA) in blood) is done in conjunction with other markers of tissue injury (See Abstract…A large proportion of extracellular vesicles isolated from plasma were identified as exosomes using a fluorescence probe specific for exosomes and three protein markers, Hsp70, CD9 and CD63, that are commonly used to identify exosome fraction.; Under BRI…Hsp70, CD9, and CD63 are used as protein markers related to tissue injury).
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over (Fernando, M. Rohan, et al. "New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes." PloS one 12.8 (2017): e0183915.) in view of Ashley et al. ("Detection of mitochondrial DNA depletion in living human cells using PicoGreen staining." Experimental cell research 303.2 (2005): 432-446., submitted in IDS on 09/15/2023) as applied to claim 12 above, and further in view of Guescini et al. ("Astrocytes and Glioblastoma cells release exosomes carrying mtDNA." Journal of neural transmission 117.1 (2010): 1-4.
Regarding Claim 18, the method of claim 12 is obvious over Fernando in view of Ashley.
The combination of Fernando and Ashley does not teach that the biological sample is obtained from:
a patient suspected of having a lung adenocarcinoma;
a patient suspected of having a traumatic brain injury, a brain trauma, a concussion, or a disease of oxidative stress; or
a patient suspected of having SARS-CoV-2 or other virus infection.
In the analogous art disclosing that astrocytes and glioblastoma cells release exosomes carrying mtdna, Guescini teaches that a patient suspected of having a a disease of oxidative stress (See Page 4…In view of the demonstration of a pathogenic role of altered mitochondria in Alzheimer’s disease (AD) (Schapira 2006), the finding that altered (rotenone-poisoned) mitochondria can migrate via TNTs (Agnati et al. 2009) has a substantial interest; Under BRI, Alzheimer’s disease (AD) is heavily linked to oxidative stress).
The limitation “a patient suspected of having a lung adenocarcinoma; a patient suspected of having a traumatic brain injury, a brain trauma, a concussion; or a patient suspected of having SARS-CoV-2 or other virus infection” is viewed as optional.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando and Ashley to include that the biological sample is obtained from: a patient suspected of having a lung adenocarcinoma; a patient suspected of having a traumatic brain injury, a brain trauma, a concussion, or a disease of oxidative stress; or a patient suspected of having SARS-CoV-2 or other virus infection, as taught by Guescini for the benefit of demonstrating the pathogenic role of altered mitochondria in Alzheimer’s disease (AD) (Guescini, Page 4), allowing for providing that bonafide exosomes, constitutively released by Glioblastoma cells and Astrocytes, can carry mtDNA, which can be, therefore, transferred between cells. This datum may help the understanding of some diseases due to mitochondrial alterations (Guescini, Abstract).
Regarding Claim 19, the method of claim 12 is obvious over Fernando in view of Ashley.
The combination of Fernando and Ashley does not teach wherein an amount of mitochondrial DNA in the sample is increased when compared to a sample obtained from a subject not having a disease.
In the analogous art disclosing that astrocytes and glioblastoma cells release exosomes carrying mtdna, Guescini teaches that wherein an amount of mitochondrial DNA in the sample is increased when compared to a sample (‘Glioblastoma and Astrocyte cells”) obtained from a subject not having a disease (See Abstract… Glioblastoma and Astrocyte cells release microvesicles, which carry mitochondrial DNA (mtDNA)… This datum may help the understanding of some diseases due to mitochondrial alterations; See Page 2… This analysis revealed the presence of mtDNA (Fig. 1b) but not of nDNA (data not shown) in the exosomal pellet of both glioblastoma cells and astrocytes, thereby teaching “an amount of mitochondrial DNA in the sample is increased when compared to a sample obtained from a subject not having a disease”.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando and Ashley to include that an amount of mitochondrial DNA in the sample is increased when compared to a sample obtained from a subject not having a disease, as taught by Guescini for the benefit of disclosing the mTDNA is present on exosomes released under disease conditions (Guescini, Abstract, Page 2), allowing for providing that bonafide exosomes, constitutively released by Glioblastoma cells and Astrocytes, can carry mtDNA, which can be, therefore, transferred between cells. This datum may help the understanding of some diseases due to mitochondrial alterations (Guescini, Abstract).
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over (Fernando, M. Rohan, et al. "New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes." PloS one 12.8 (2017): e0183915.) in view of Ashley et al. ("Detection of mitochondrial DNA depletion in living human cells using PicoGreen staining." Experimental cell research 303.2 (2005): 432-446., submitted in IDS on 09/15/2023) as applied to claim 12 above, and further in view of Goetzl et al. ("Traumatic brain injury increases plasma astrocyte‐derived exosome levels of neurotoxic complement proteins." The FASEB Journal 34.2 (2020): 3359-3366.
Regarding Claim 21, the method of claim 12 is obvious over Fernando in view of Ashley.
Fernanado teaches that the biological sample is from a subject (See Abstract…Plasma was obtained; See Page 2… Blood samples were obtained from …donors).
The combination of Fernando and Ashley does not explicitly teach that the biological sample is from a subject suspected of having a traumatic brain injury and one or more proteins in the extracellular vesicles from plasma are up-regulated: complement factor D.
In the analogous art of traumatic brain injury increases plasma astrocyte-derived exosome levels of neurotoxic complement proteins, Goetz teaches that the biological sample is from a subject suspected of having a traumatic brain injury: complement factor D (CFD) (See Abstract… Possible involvement of complement (C) systems in the pathogenesis of traumatic brain injury (TBI) was investigated by quantifying Cproteins in plasma astrocyte-derived exosomes (ADEs) of subjects with sports-related TBI (sTBI) and TBI in military veterans (mtTBI) without cognitive impairment.) and one or more proteins in the extracellular vesicles (See Abstract… quantifying Cproteins in plasma astrocyte-derived exosomes (ADEs)) from plasma are up-regulated (See Abstract… elevated levels of factor D (complementary factor D), Bb, and MBL).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando and Ashley to include that the biological sample is from a subject suspected of having a traumatic brain injury and one or more proteins in the extracellular vesicles from plasma are up-regulated, as taught by Goetzl for the benefit of identifing abnormalities in plasma ADE levels of complement mediators and inhibitors for groups of patients with TBI of different severity and at different times after TBI (Goetzl, Introduction), which allows to demonstrate that ADE complement and other protein cargoes should be meaningfully considered when evaluating biomarkers of TBI and neurodegenerative diseases as their levels are significantly higher than those of NDEs from the same patients demonstration (Goetzl, Discussion, Page 3365).
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Fernando, M. Rohan, et al. "New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes." PloS one 12.8 (2017): e0183915.) in view of Ashley et al. ("Detection of mitochondrial DNA depletion in living human cells using PicoGreen staining." Experimental cell research 303.2 (2005): 432-446., submitted in IDS on 09/15/2023) as applied to claim 12 above, and further in view of Takeuchi et al. ("Decrease in plasma adiponectin level and increase in adiponectin immunoreactivity in cortex and hippocampus after traumatic brain injury in rats." Turkish Neurosurgery (2012).
Regarding Claim 22, the method of claim 12 is obvious over Fernando in view of Ashley.
The combination of Fernando and Ashley does not explicitly teach that the biological sample is from a subject suspected of having a traumatic brain injury and one or more proteins in the extracellular vesicles from plasma are down-regulated: haptoglobin (Hp); von Willebrand factor (VWF); Corticosteroid-binding globulin (Q06770); Coagulation factor XIII B chain (Q07968); Alpha- 1B-glycoprotein (Q19LI2); Adiponectin (Q60994); Alpha-2-macroglobulin-P (Q6GQT1);Coagulation factor XIII A chain (Q8BH61); Fibrinogen beta chain; Fibrinopeptide B; Fibrinogen beta chain (Q8KOE8); Fibrinogen gamma chain (Q8VCM7); CD5 antigen-like (Q9QWK4); Proteasome subunit alpha type-1 (Q9R1P4); or Proteasome subunit alpha type-5 (Q9Z2U1).
In the analogous art of the decrease in plasma adiponectin level and increase in adiponectin immunoreactivity in cortex and hippocampus after traumatic brain injury in rats, Takeuchi teaches that the biological sample is from a subject suspected of having a traumatic brain injury (See Abstract… Adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury using the Dragonfly device.) and one or more proteins (‘adiponectin’) in the extracellular vesicles (Adiponectin are found in extracellular vesicles as evidenced by Constantin et al. ) from plasma are down-regulated: Adiponectin (See Abstract… The plasma adiponectin levels gradually decreased and were significantly lower at 48 h and 72h after injury than before injury).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando and Ashley to include that the biological sample is from a subject suspected of having a traumatic brain injury and one or more proteins in the extracellular vesicles from plasma are down-regulated: …Adiponectin, as taught Takeuchi for the benefit of disclosing that adiponectin might participate in the pathophysiological process occurring after TBI (Takeuchi, Conclusion), allowing for the presentation of the hyposthesis that adiponectin may participate in cerebroprotective mechanisms through its anti-inflammatory and/or anti-apoptotic actions after TBI. In addition, we consider that the accumulation (recruitment) of adiponectin in the brain might contribute to the decrease in the plasma adiponectin levels (Takeuchi, Page 353).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Fernando, M. Rohan, et al. "New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes." PloS one 12.8 (2017): e0183915.) in view of Ashley et al. ("Detection of mitochondrial DNA depletion in living human cells using PicoGreen staining." Experimental cell research 303.2 (2005): 432-446., submitted in IDS on 09/15/2023) as applied to claim 12 above, and further in view of Kulbe et al. ("Current status of fluid biomarkers in mild traumatic brain injury." Experimental neurology 275 (2016): 334-352) in view of
Regarding Claim 23, the method of claim 12 is obvious over Fernando in view of Ashley.
The combination of Fernando and Ashley does not explicitly teach measuring expression levels of one or more proteins in the biological sample selected from: Serum Amyloid.
In the analogous art of fluid biomarkers in mild traumatic brain injury, Kulbe teaches measuring expression levels of one or more proteins (See Table 3… Identification of Serum Amyloid in serum) in the biological sample (See Page 5…Blood (serum and plasma)) selected from: Serum Amyloid (See Table 3… Identification of Serum Amyloid in serum).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando and Ashley to include that measuring expression levels of one or more proteins in the biological sample selected from: Serum Amyloid, as taught Kulbe, for the benefit of determining Serum Amyloid as a candidate biomarker to identify children with mild AHI that would benefit from radiologic evaluation (Kulbe, Page 20), allowing for the provision of an approach that has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers (Kulbe, Abstract).
The combination of Fernando, Ashley and Kulbe does not teach:
applying an algorithm to the measured protein expression,
the algorithm generating a traumatic brain injury score based on a comparison of the measured expression levels to reference levels, wherein the algorithm is selected from a machine learning algorithm, a clustering algorithm, a support vector machine, or combinations thereof; and
In the analogous art of a computer-implemented method for generating an assessment of traumatic brain injury (TBI) includes a TBI assessment computer receiving structural imaging data acquired by performing a structural imaging scan on an individual and generating a structural imaging score based on the structural imaging data, Odry teaches that:
applying an algorithm (See Para 0023… an automated algorithm that takes into account several imaging modalities and uses their specificity to combine findings into one score) to the measured protein expression (referred to as brain features [Para 0011]; Examiner submits that brain lesions (areas of damaged tissue) often comprise or are surrounded by accumulated proteins),
the algorithm generating a traumatic brain injury score based on a comparison of the measured expression levels to reference levels, wherein the algorithm is selected from a machine learning algorithm, a clustering algorithm, a support vector machine, or combinations thereof (See Page 0023…the disclosed techniques utilize an automated algorithm that takes into account several imaging modalities and uses their specificity to combine findings into one score; See Para 0049…processors 620 may also be employed in a multi-processing arrangement to execute the one or more sequences of instructions contained in system memory 630; Under BRI, Examiner submits that processors in a multi-processing arrangement are a critical hardware infrastructure used to execute machine learning tasks efficiently, thereby teaching “machine learning algorithm).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando, Ashley and Kulbe to include applying an algorithm to the measured protein expression,
the algorithm generating a traumatic brain injury score based on a comparison of the measured expression levels to reference levels, wherein the algorithm is selected from a machine learning algorithm, a clustering algorithm, a support vector machine, or combinations thereof, as taught by Odry, for the benefit of utilizing an automated algorithm that takes into account several imaging modalities and uses their specificity to combine findings into one score (Odry, Para 0023), allowing for the provision of a system for TBI assessment which provides for qualification of severity, along with quantification of related information (Odry, Para 0003).
The combination of Fernando, Ashley, Kulbe and Odry does not teach:
identifying the subject with the higher traumatic brain injury score as having a higher clinical outcome score for traumatic brain injury.
In the analogous art of method for reducing the risk of neurological injury to a neonatal human child, Edgar teaches:
identifying the subject with the higher traumatic brain injury score (‘Z-score’) as having a higher clinical outcome score for traumatic brain injury (See Page 20… As shown in Figure 12, in patients with evidence of diffuse brain injury (see Figs. 12-12C, black arrows showing high Z-scores in many brain regions)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Fernando, Ashley, Kulbe and Odry to include identifying the subject with the higher traumatic brain injury score as having a higher clinical outcome score for traumatic brain injury, as taught by Edgar, for the benefit of determining the evidence of brain injury (Edgar, Page 20), allowing for the provision of a means to detect and monitor for traumatic brain injury, especially mild traumatic brain injury, in order to rapidly and accurately provide a diagnosis and to ensure rapid medical treatment, which is important for a more effective and successful therapy (Edgar, Page 2).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Constantin et al. (“Extracellular vesicles from adipose tissue stem cells in diabetes and associated cardiovascular disease; pathobiological impact and therapeutic potential." International Journal of Molecular Sciences 21.24 (2020): 9598.) teaches that Adiponectin, as well as a small amount of resistin were found also in small EVs from serum (See Section 3…Extracellular Vesicles from Adipose Tissue Stem Cells).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
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