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 Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-7, 15-23 and 25-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McQuiston et al (US PGPub 2018/0364261).
Regarding Claims 1 and 7, McQuiston et al teaches a method for detecting and/or diagnosing a traumatic brain injury in a subject comprising detecting and/or measuring at least one biomarker in a biological sample obtained from said subject (see abstract and [0009]) and wherein said biological sample is obtained from a subject (see [0022] and [0047]).
Regarding Claims 2-3, McQuiston et al teaches that the biological sample is a fluid, such as urine (see [0189] and [0445]).
Regarding Claim 4, McQuiston et al teaches that the biomarkers are detected and/or measured in the gaseous phase of the biological sample (see [0080]).
Regarding Claims 5-6, McQuiston et al teaches that said traumatic brain injury is mild or moderate, such as a concussion (see [0005] and [0201]).
Regarding Claims 15 and 28, McQuiston et al teaches that said detecting and/or measuring of at least one biomarker comprises gas chromatography and/or mass spectrometry, and/or ion mobility spectrometry (see [0142] or [0225]).
Regarding Claims 16 and 26, McQuiston et al teaches that aid at least one biomarker is measured and/or detected by a handheld device (see [0465]).
Regarding Claims 17-21, McQuiston et al teaches that said biological sample is obtained from the subject within 48 hours of a purported traumatic brain injury, more specifically within 24 hours, 12 hours, 6 hours or 1 hour of a purported traumatic brain injury (see [0019] and [0483]).
Regarding Claim 22, McQuiston et al teaches that the presence and increase in the at least one biomarker indicates the subject has a traumatic brain injury (see [0181] and [0242]-[0243]).
Regarding Claim 23, McQuiston et al teaches administering a traumatic brain injury therapeutic to the subject determined to have a traumatic brain injury (see [0048], [0119] and [0269]).
Regarding Claim 25, McQuiston et al teaches a device for detecting and/or diagnosing a traumatic brain injury in a subject, said device configured to detect and/or measure at least one biomarker in a biological sample obtained from said subject (see [0009], [0225] and [0402]).
Regarding Claim 27, McQuiston et al teaches that said device is configured to detect and/or measure at least one biomarker in a fluid (see [0189]-[0190]) and/or gas (see [0080]).
Claim(s) 1-3, 5-7, 15-16, 22-23 and 25-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Harel et al (US PGPub 2020/0003772).
Regarding Claims 1 and 7, Harel et al teaches a method for detecting and/or diagnosing a traumatic brain injury in a subject comprising detecting and/or measuring at least one biomarker in a biological sample obtained from said subject (see [0194] and [0201]) and wherein said biological sample is obtained from a subject (see [0079], [0173] and [0188]).
Regarding Claims 2-3, Harel et al teaches that the biological sample is a fluid, such as urine (see [0012] and [0079]).
Regarding Claims 5-6, Harel et al teaches that said traumatic brain injury is mild or moderate, such as a concussion (see [0179] and [0219]).
Regarding Claims 15 and 28, Harel et al teaches that said detecting and/or measuring of at least one biomarker comprises gas chromatography and/or mass spectrometry, and/or ion mobility spectrometry (see [0199]).
Regarding Claims 16 and 26, Harel et al teaches that aid at least one biomarker is measured and/or detected by a portable device (see [0074]).
Regarding Claim 22, Harel et al teaches that the presence and increase in the at least one biomarker indicates the subject has a traumatic brain injury (see [0012] and [0197]).
Regarding Claim 23, McQuiston et al teaches administering a traumatic brain injury therapeutic to the subject determined to have a traumatic brain injury (see
Regarding Claim 25, Harel et al teaches a device for detecting and/or diagnosing a traumatic brain injury in a subject, said device configured to detect and/or measure at least one biomarker in a biological sample obtained from said subject (see [0198]).
Regarding Claim 27, Harel et al teaches that said device is configured to detect and/or measure at least one biomarker in a fluid (see [0012]).
Claim(s) 1-7, 15-23 and 25-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hayes et al (US PGPub 2014/0303041).
Regarding Claims 1 and 7, Hayes et al teaches a method for detecting and/or diagnosing a traumatic brain injury in a subject comprising detecting and/or measuring at least one biomarker in a biological sample obtained from said subject (see [0017] and [0090]) and wherein said biological sample is obtained from a subject (see [0104] and [0112]).
Regarding Claims 2-3, Hayes et al teaches that the biological sample is a fluid, such as urine (see [0033], [0088] and [0096]).
Regarding Claim 4, Hayes et al teaches that the biomarkers are detected and/or measured in the gaseous phase of the biological sample (see [0128] and [0139]).
Regarding Claims 5-6, Hayes et al teaches that said traumatic brain injury is mild or moderate, such as a concussion (see [0075] and [0077]).
Regarding Claims 15 and 28, Hayes et al teaches that said detecting and/or measuring of at least one biomarker comprises gas chromatography and/or mass spectrometry, and/or ion mobility spectrometry (see [0112], [0115] and [0128]).
Regarding Claims 16 and 26, Hayes et al teaches that aid at least one biomarker is measured and/or detected by a handheld device (see [0087]).
Regarding Claims 17-21, Hayes et al teaches that said biological sample is obtained from the subject within 48 hours of a purported traumatic brain injury, more specifically within 24 hours, 12 hours, 6 hours or 1 hour of a purported traumatic brain injury (see [0046], [0150], [0160] and [0168]).
Regarding Claim 22, Hayes et al teaches that the presence and increase in the at least one biomarker indicates the subject has a traumatic brain injury (see abstract, [0096] and [0101]).
Regarding Claim 23, Hayes et al teaches administering a traumatic brain injury therapeutic to the subject determined to have a traumatic brain injury (see [0164]).
Regarding Claim 25, Hayes et al teaches a device for detecting and/or diagnosing a traumatic brain injury in a subject, said device configured to detect and/or measure at least one biomarker in a biological sample obtained from said subject (see abstract and [0017]).
Regarding Claim 27, Hayes et al teaches that said device is configured to detect and/or measure at least one biomarker in a fluid (see [0073]) and/or gas (see [0128]).
Claim(s) 1-7, 15-23 and 25-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Svetlov et al (US PGPub 2015/0268252).
Regarding Claims 1 and 7, Svetlov et al teaches a method for detecting and/or diagnosing a traumatic brain injury in a subject comprising detecting and/or measuring at least one biomarker in a biological sample obtained from said subject (see [0002], [0004] and [0066]-[0067]) and wherein said biological sample is obtained from a subject (see [0004], [0108] and [0120]).
Regarding Claims 2-3, Svetlov et al teaches that the biological sample is a fluid, such as urine (see [0107]-[0108]).
Regarding Claim 4, Svetlov et al teaches that the biomarkers are detected and/or measured in the gaseous phase of the biological sample (see [0181]).
Regarding Claims 5-6, Svetlov et al teaches that said traumatic brain injury is mild or moderate, such as a concussion (see [0076], [0080] and [0168]).
Regarding Claims 15 and 28, Svetlov et al teaches that said detecting and/or measuring of at least one biomarker comprises gas chromatography and/or mass spectrometry, and/or ion mobility spectrometry (see 0121]).
Regarding Claims 16 and 26, Svetlov et al teaches that aid at least one biomarker is measured and/or detected by a handheld device (see [0172]).
Regarding Claims 17-21, Svetlov et al teaches that said biological sample is obtained from the subject within 48 hours of a purported traumatic brain injury, more specifically within 24 hours, 12 hours, 6 hours or 1 hour of a purported traumatic brain injury (see [0144], [0167]-[0168] and [0198]).
Regarding Claim 22, Svetlov et al teaches that the presence and increase in the at least one biomarker indicates the subject has a traumatic brain injury (see [0067] and [0070]).
Regarding Claim 23, Svetlov et al teaches administering a traumatic brain injury therapeutic to the subject determined to have a traumatic brain injury (see [0130], [0146] and [0164]).
Regarding Claim 25, Svetlov et al teaches a device for detecting and/or diagnosing a traumatic brain injury in a subject, said device configured to detect and/or measure at least one biomarker in a biological sample obtained from said subject (see [0010] and [0172]-[0178]).
Regarding Claim 27, Svetlov et al teaches that said device is configured to detect and/or measure at least one biomarker in a fluid (see [0107]-[0108]) and/or gas (see [0181]).
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.
Claim(s) 8, 9, 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over McQuiston et al (or Hayes et al or Harel et al or Svetlov et al) as applied to claim 1 above, and further in view of Kimball et al (with references taken from US PGPub 20240085413).
Regarding Claims 8-9, 13 and 14, none of McQuiston et al (or Hayes et al or Harel et al or Svetlov et al) explicitly discloses that at least one biomarker is an aliphatic ketone, which comprises a ketone group at position 2, such as 3-methyl-4-hexen-2-one.
However, in the analogous art of methods and devices for the discrimination of pathogens based on volatile compound patterns, WO Kimball teaches n assay is provided for rapidly distinguishing a source of infection in a mammalian subject by detecting in a biological sample and comparing the levels of one, two or all three of the VOCs 2-ethyl-l -hexanol, acetophenone, and 3-methyl-4-hexen-2-one (which is an aliphatic ketone, with the ketone at position 2). In one embodiment, the levels of these VOCs are distinguishable by comparison to known levels in a standard for a bacterial infection and a standard for viral infection (see [0009]). Furthermore, Kimball et al teaches assays which may utilize steps to detect increased or decreased 3-methyl-4-hexen-2-one levels relative to a suitable standard as stated above. In one embodiment, for classification of the sample as a viral infection, the assay permits detection of increased 3-methyl-4-hexen-2-one relative to a reference standard for Gram-positive bacterial infection and/or a reference standard for Gram-negative infection and/or a reference standard for a febrile disease caused by a non-infectious circumstance, e.g., trauma (see [0047]). It would have been obvious to one of ordinary skill in the art to detect an aliphatic ketone (with ketone at position 2) such as 3-methyl-4-hexen-2-one (as taught by Kimball et al), as 3-methyl-4-hexen-2-one is a known VOC, for the benefit of effectively detecting a viral infection, a bacterial infection or a febrile disease.
Claim(s) 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over McQuiston et al (or Hayes et al or Harel et al or Svetlov et al) as applied to claim 1 above, and further in view of Kimball et al (“ Alterations of the volatile metabolome in mouse models of Alzheimer’s disease), hereinafter referred to as Kimball npl, cited in the IDS.
Regarding Claims 13-14, McQuiston et al (or Hayes et al or Harel et al or Svetlov et al) does not explicitly disclose that said at least one biomarker comprises phenylacetone.
However, in the analogous art of biomarkers associated with Alzheimer’s disease, Kimball npl teaches the use of phenylacetone as a biomarker for detecting/diagnosing Alzheimer’s, wherein Kimball npl teaches a metabolomic approach to identify chemical profile differences between APP and NTg mouse urinary odor by means of headspace GC/MS, where phenylacetone significantly increased in APP transgenic mice across all strains (p = 0.0044). Furthermore, Kimball npl teaches that the finding of elevated phenylacetone among both juvenile and aged APP mice in this study indicate a metabolic abnormality throughout the life span in these mice, consistent with altered metabolic properties in persons with AD (see pages 4-5). It would have been obvious to one of ordinary skill in the art to detect phenylacetone, as taught by Kimball npl, for the benefit of effectively indicating a metabolic abnormality throughout the life span in these mice, consistent with altered metabolic properties in persons with AD.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over McQuiston et al (or Hayes et al or Harel et al or Svetlov et al) as applied to claim 23 above, and further in view of Kaddurah-Daouk et al (US PGPub 2020/0241011).
Regarding Claim 24, McQuiston et al (or Hayes et al or Harel et al or Svetlov et al) does not explicitly disclose that said traumatic brain injury therapeutic comprises a branched chain amino acid.
However, in the analogous art of compositions and methods for use in the analysis of broad metabolic changes associated with neurological disorders, Kaddurah-Daouk et al teaches obtaining a sample from a subject; b) performing biochemical analysis on the sample to measure or detect a level of at least one biomarker metabolite, wherein the at least one biomarker metabolite is selected from the group consisting of a branched-chain amino acid biomarker metabolite, a glutamate biomarker metabolite, a tryptophan biomarker metabolite, a tyrosine biomarker metabolite, a 2 amino adipic acid biomarker metabolite, a phosphatidylcholine biomarker metabolite, a lysophosphatidylcholine biomarker metabolite, and combinations thereof, wherein if the subject has a level of the at least one biomarker metabolite that is lower that the level of the at least one biomarker metabolite in a control sample, the subject is predicted to develop Alzheimer's disease or have an increased risk of Alzheimer's disease, and c) initiating treatment for Alzheimer's disease in the subject predicted to develop Alzheimer's disease (see [0014]). Furthermore, Kaddurah-Daouk et al teaches that association between the BCAA and genes that are involved directly or indirectly with cognitive diseases, such as AD. For example, low levels of valine was associated with CDYL which is known to regulate REST, which is associated with cognitive disorders, such as AD, in men (see [0035]). In addition, Kaddurah-Daouk et al teaches that the method further comprises initiating treatment for Alzheimer's disease in the subject diagnosed with Alzheimer's disease. In some embodiments, if the subject is male and diagnosed with Alzheimer's disease or determined to have an increased risk of developing Alzheimer's disease, the treatment comprises administering a drug that modulates KLF15, CDYL, CDH22, SLC35C2, ADAM32, and/or ADAM9 activity. In some embodiments, if the at least one metabolic biomarker is valine, the drug modulates the activity of CDYL, KLF15 and/or CCDC37. In some embodiments, if the at least one metabolic biomarker is leucine, the drug modulates the activity of CDH22 and/or SLC35C2. In some embodiments, if the at least one metabolic biomarker is isoleucine, the drug modulates the activity of ADAM9 and/or ADAM32. In some embodiments, treatment comprises a branched-chain amino acid, such as valine, isoleucine, and/or leucine (see [0057]).
It would have been obvious to one of ordinary skill in the art to utilize a branched chain amino acid as the traumatic brain injury therapeutic, as taught by Kaddurah-Daouk et al, for the benefit of providing an effective (and gender-specific) treatment or therapy for Alzheimer’s disease by modulating KLF15, CDYL, CDH22, SLC35C2, ADAM32, and/or ADAM9 activity.
Allowable Subject Matter
Claim 10-12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding Claims 10-12, none of the cited prior art teaches or fairly suggests that said aliphatic ketone further comprises a double bond between carbons 3 and 4 or that said at least one biomarker comprises 3-octen-2-one, 3-nonen-2-one, and/or 3-decen-2-one.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Van Meter (US PGPub 20220074953) discloses methods, compositions and kits useful in the detection, assessment, diagnosis, prognosis and/or treatment of brain injuries, especially mild traumatic brain injury (mTBI) or concussion, are based upon detection of changes in levels of certain protein biomarkers in a subject undergoing testing, or upon detection of changes in levels of certain protein biomarkers in conjunction with neuroimaging analyses to detect changes in vascular or blood brain barrier (BBB) permeability in the brain, or to detect damage to fiber tracts in the brain, in which changes in biomarker levels correlate with detection of changes in BBB permeability or in brain fiber tract or white matter damage in a subject with brain injury such as mTBI or concussion (see abstract).
Van Keuren-Jensen et al (US PGPub 20180258483) discloses methods of determining the risk of a subject developing mTBI. The methods generally include obtaining a biological sample from a subject; measuring the biological sample for an amount of at least one microRNA marker selected from the group consisting of the biomarkers selected from biomarkers listed in any one of Tables 1-65; and comparing the amount of the at least microRNA marker with the amount of the at least one microRNA marker in a control biological sample, wherein a change in the amount of the at least one microRNA marker from the subject compared with the control is indicative of the subject having an increased risk for mTBI (see [0010]).
Van Eyk et al (US PGPub 2019/038382) discloses methods for diagnosing and evaluating a subject that has sustained or may have sustained an injury to the head, such as a traumatic brain injury (TBI). In particular, the present disclosure identifies various biomarkers, the detection and/or differential expression of which can be used to assess the presence or absence of a TBI in a subject, and can be used as a basis for diagnosing a subject as having a specific type of TBI (e.g., severe TBI or subclasses of mild TBI). The various TBI biomarkers can be detected individually or in combination and can be used as an important diagnostic, prognostic, and/or TBI risk stratification tool as part of assessing a subject's TBI status (see abstract).
Belli et al (US PGPub 2018/0127828) discloses kits, systems and methods for diagnosing and/or monitoring traumatic brain injury (TBI). More particularly, the present invention relates to the diagnosis and monitoring of TBI using miRNA biomarkers (see [0003]).
Rai et al (US PGPub 2023/0135030) discloses methods and systems for diagnosis, detection, monitoring, and treatment of traumatic brain injury are described. The methods and systems include detection of salivary biomarkers associated with brain injury in a human subject, one application of which is to determine whether the subject has sustained a concussion or a more severe traumatic brain injury (TBI). Detection of the salivary biomarkers can also provide a basis to determine that a subject can safely return to play in an athletic event and can provide a basis to evaluate the efficacy of particular treatments. The methods and systems may be implemented, for example, by means of a kit (see abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER WECKER whose telephone number is (571)270-1109. The examiner can normally be reached 9:30AM - 6 PM EST M-F.
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/JENNIFER WECKER/ Primary Examiner, Art Unit 1797
