DETAILED ACTION
Claims 50-143 are pending.
Election/Restrictions
Applicant’s election of group II claims 69-87 in the reply filed on 09/03/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 50-68 and 88-143 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/03/2025.
Claims 69-87 are under examination.
Priority
Claims 69-87 do not qualify for the earlier priority date of the provisional application 63/169,193 because ‘193 does not teach or reference a method for discriminating a tauopathy.
Due to claims 69-87 of the instant application not being supported by ‘193, claims 69-87 of the instant application do not qualify for the earlier filing date of the provisional application 63/169,193.
The earliest priority date for claims 69-87 is the 371 date 03/31/2022.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 03/28/2024, 01/21/2025, 07/08/2025, and 10/20/2025 have been considered by the examiner.
Claim Objections
Claim 69 is objected to because of the following informalities: The claim recites an abbreviation and/or acronym of “CSF” which should be spelled out at their first usage followed by the abbreviation/acronym in parenthesis. Appropriate correction is required.
Claims 71-74, 77, 79-80, and 82-83 are objected to because of the following informalities: The claim recites an abbreviation and/or acronym of “AD” which should be spelled out at their first usage followed by the abbreviation/acronym in parenthesis. Appropriate correction is required.
Claims 74 and 76 are objected to because of the following informalities: The claim recites an abbreviation and/or acronym of “FTD” which should be spelled out at their first usage followed by the abbreviation/acronym in parenthesis. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 69-87 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 69, 73-74, 76, 79-80, 82-83, 85, and 87 recite “from a healthy state”. However, it is unclear what is considered a “healthy state”. The instant specification fails to explicitly teach what a “healthy state” refers to. The instant specification states discriminating a MAPT R406W tauopathy from Alzheimer’s disease, 4R-tauopathy and a healthy state (see [0010], [0011], [0030], and [0033]). The instant specification mentions a “healthy” subject refers to a subject, or group of subjects, who are clinically determined to not have a tauopathy or A3 amyloidosis (including but not limited to Alzheimer’s disease), based on a qualitative or quantitative test rest (see [0071]). However, the instant application does not teach any criterial that would qualify something as a “healthy state”. It is unclear if a “healthy state” is a population of people who have normal levels of p-tau and Aβ 42/40. Further, it is unclear what levels/measurements are considered a “healthy state”.
Claims 71-72, 80, and 83 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 71-72, 80, and 83 recite “value of the and an Aβ 42/40 value…”. It is unclear what “value of the” is referring to. The instant application fails to explicitly teach what “value of the” is referring to. One of skill in the art would not know what the inventor is comparing the value to. The limitations of the claims are unknown.
Claims 80 and 83 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 80 and 83 recite “normal” values. However, it is unclear what is considered “normal” values. The instant application teaches that a “normal population” refers to a subject, or group of subjects, who are clinically determined to not have a tauopathy or A3 amyloidosis (including but not limited to Alzheimer’s disease), based on a qualitative or quantitative test rest (see [0071]). However, the instant specification does not recite what values would be considered “normal”. The instant specification recites “a normal Aβ 42/40 value” in multiple paragraphs, including [0008], but does not provide any criteria or range to what qualifies as “normal”. Thus, it is unclear what levels/measurements are considered “normal”.
Claim 73 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 73 recites “calculating determining a composite pT217/T217 x Aβ 42/40…”. It is unclear what is being calculated. The instant application fails to explicitly teach or even mention what is being calculated. Further, the claim recites “a composite pT217/T217 x Aβ 42/40 value”. It is unclear if the x is for multiplication, some X factor, or a placeholder for “and”. It is unclear whether the composite is merely a multiplication of two ratios (pT217/T217 and Aβ 42/40). If that is the case, suggested language would be i.e., “…further comprising calculating a composite value, wherein the calculation is pT217/217 x Aβ 42/40, wherein an increased composite value relative to a healthy control population indicated the subject as having or at an increased risk for Alzheimer’s Disease (AD) or non-Alzheimer’s Disease (non-AD) tauopathy”, or “…further comprising calculating a composite value, wherein pT217/T217 is multiplied by Aβ 42/40, wherein an increased composite value relative to a healthy control population indicated the subject as having or at an increased risk for Alzheimer’s Disease (AD) or non-Alzheimer’s Disease (non-AD) tauopathy”.
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 69-87 are rejected under 35 U.S.C. 101 because the claimed method is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 1
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03
Regarding instant claim 69, Example 43 of “2019 PEG” is particularly enlightening
because the fact pattern of claim 1 of example 43 is most similar to the instant application
claims.
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 1, the claim is directed to a process, which is one of the statutory categories of invention as the claim recites “A treatment method comprising: (a) calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype; (b) administering a treatment to the patient having a non-responder phenotype.” (Step 1: YES).
Similarly, instant claim 69 is directed to a statutory method that measures one or more phospho-tau and Aβ species in a blood sample from a subject, then using that measurement to discriminate a tauopathy from a healthy state (Step 1: YES).
Step 2A, Prong 1: Does the claim recite a judicial exception?
This part of the eligibility analysis evaluates whether the claim recites a judicial
exception. As explained in MPEP 2106.04(II), 2019 Revised Patent Subject MatterEligibility Guidance, PEG and the October 2019 Update, a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim.
Regarding instant claims 69-87, Example 43 of the “2019 PEG” shows a similar fact pattern.
Regarding claim 1 of Example 43, Limitation (a) in the claim recites several nature-based product limitations including C11, C13, and the blood sample, which raises the question of whether the markedly different characteristics analysis should be used to determine if the nature-based product limitations are product of nature exceptions. For a process claim, the general rule is that the claim is not subject to the markedly different analysis for nature-based products used in the process. MPEP 2106.04(c)(I)(C). While there is an exception to this general rule for process claims that are drafted in such a way that they are no different in substance than a product claim, claim 1 does not invoke this exception because review of this claim indicates that it is focused on a process of determining how much C11 and C13 is present in the blood sample and then treating a patient in accordance with that determination, and is not focused on the products per se. Thus, the general rule expressed in the MPEP applies, meaning that the markedly different characteristics analysis is not performed on the recited nature-based product limitations, and the claim is not considered to “recite” any products of nature for purposes of further eligibility analysis.
Similarly, instant claim 69 recites several nature-based product limitations including CSF, blood samples, one or more phospho-tau and Aβ species. While there is an exception to this general rule for process claims that are drafted in such a way that they are no different in substance than a product claim, instant claim 69 does not invoke an exception because review of this claim indicates that it is focused on a process of determining the presence/levels of phosphor-tau and Aβ species is present in a CSF or blood sample and then using those values to discriminate a tauopathy from a healthy state. Thus, the general rule expressed in the MPEP applies, meaning that the markedly different characteristics analysis is not performed on the recited nature-based product limitations, and the claim is not considered to “recite” any products of nature for purposes of further eligibility analysis. However, like claim 1 in Example 43, the instant claim 69 must then be further reviewed for any other type of judicial exception.
Example 43 of “2019 PEG” continues the analysis to determine whether it recites any other type of judicial exception,per Step 2A, prong 1, the claim recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” and according to broadest reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the ratio of C11 to C13 that can be used to identify whether the patient has the non-respondent phenotype.
Specifically, limitation (a) in claim 1 of Example 43 of the “2019 PEG” recites “calculating
a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic
Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder
phenotype,” which has a BRI that requires performing an arithmetic calculation (division) in
order to obtain the ratio of C11 to C13 levels, and then using this ratio to identify whether the
patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or
greater and thus is not responding, or will not respond, to glucocorticoids). This limitation
therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the
2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG
Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping
of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be
practically performed in the human mind, and is in fact performed in the human mind on a daily
basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature
of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract
ideas.
In addition, limitation (a) describes a naturally occurring relationship between the ratio
of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a
law of nature. Accordingly, limitation (a) recites a judicial exception (an abstract idea that falls
within the mathematical concept and mental process groupings in the “2019 PEG”, and a law of
nature), and the analysis must therefore proceed to Step 2A Prong Two.
Instant claim 69 recites “(b) quantifying, in the processed sample, a phospho-tau value and an Aβ 42/40 value, wherein a significantly different phospho-tau value and/or Aβ 42/40 value discriminates a tauopathy from a healthy state” which describes a naturally occurring relationship between the one or more phosphor-tau and Aβ 42/40 and correlating it to a tauopathy, and thus is considered to recite a law of nature. Further, instant claim 69 recites using the obtained phosphor-tau and Aβ 42/40 values to discriminate between a tauopathy and a healthy state, which is directed towards an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion)). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind.
Consequently, like example 43, instant claim 69 recites the judicial exception of applying and using a law of nature and an abstract idea.
Dependent instant claims 70-87 contain limitations that fall under a judicial exception. The dependent claims recite measurements of biomarkers and/or natural correlations of the presence and levels of biomarkers with a disease. Further, instant claims 71-73, 77, 79-80, 82-83, 85, and 87 recite “relative to” which has a BRI that requires a comparison between a subject’s biomarker levels to a healthy subject’s biomarker level, which is directed towards an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion)). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Lastly, Instant claim 73 recites calculating “a composite pT217/T217 x Aβ 42/40 value”, which has a BRI that requires performing an arithmetic calculation (multiplication) in order to obtain a value relative to a healthy control in order to indicate the subject as being at risk for AD or a non-AD tauopathy. This limitation therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be practically performed in the human mind, and is in fact performed in the human mind on a daily basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract ideas.
Accordingly, instant claims 69-87 recite a judicial exception (a law of nature and an abstract idea that falls within the mental process groupings) and the analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
Regarding instant claim 69, Example 43 of “2019 PEG” shows a similar fact pattern.
In claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a
whole does not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional
elements recited in the claim beyond the judicial exception, and (b) evaluating those additional
elements individually and in combination to determine whether the claim as a whole integrates
the exception into a practical application. Besides the abstract idea, the claim 1 of example 43
of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient
having a non-responder phenotype”. Although this limitation indicates that a treatment is to be
administered, it does not provide any information as to how the patient is to be treated, or what
the treatment is, but instead covers any possible treatment that a doctor decides to administer
to the patient. In fact, this limitation is recited at such a high level of generality that it does not
even require a doctor to take the calculation step’s outcome (the patient’s phenotype) into
account when deciding which treatment to administer, making the limitation’s inclusion in this
claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to
meaningfully limit the claim because it does not require any particular application of the recited
calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial
exception. Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the
recited judicial exception into a practical application and the claim is therefore directed to the
judicial exception.
Similarly, instant claim 69 does not have additional elements that would integrate the judicial exception cited above into a practical application. In comparison, claim 1 of Example 43 did not pass step 2A prong 2 with step of general treatment, instant claim 69 does not even recite any steps of treatment. Example 43 failed with the step of general treatment, instant claim 69 does not even recite a further active step, let alone a step for treatment.
Therefore, instant claim 69 does not integrate the judicial exception into a practical application.
Step 2B: Does the claim recite significantly more?
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2B, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element in limitation (b), which does not require any particular application of the recited calculation and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept (Step 2B: NO). The claim is not eligible.
Similarly, instant claim 69 recites the additional limitation of (a) providing a processed CSF or blood sample obtained from a subject that is enriched for one or more phosphor-tau and Aβ species which recites measuring naturally occurring biomarkers in a sample from a subject which are mere instructions of obtaining a judicial exception and cannot be considered an inventive concept. Accordingly, instant claim 69 is not eligible (STEP 2B: NO).
Instant claims 69-87 are rejected as ineligible under 35 USC 101.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
1.Claims 69-70, 73, 75, 78-79, 81-82, and 84-87 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Barthelemy et al., (WO 2019213612A1) (IDS filed on 03/28/2024).
Regarding claim 69, Barthelemy teaches a method of discriminating a tauopathy, the method comprising (a) providing a processed CSF or blood sample obtained from a subject (see [0060] “An isolated tau sample, as used herein, refers to a composition comprising tau, wherein tau has been purified from blood or cerebrospinal fluid (CSF) obtained from a subject.”),
wherein the CSF or blood sample is enriched for one or more phospho-tau and Aβ species (see [0139] “Our results demonstrate that several phosphorylated residues are significantly enriched in the CSF compared to brain extracts, such as T217, T231, T153 and T111. All are proline-directed sites, are potential substrates of GSK-3P protein kinase, and may be subject to kinase-dependent regulation. Unlike pT217, pS214 was not elevated in the CSF compared to the brain. This extracellular enrichment of pT217 over pS214 agreed with kinetic differences we previously identified within cells for these isoforms (Sato et al., 2018), with pT217 having a shorter turnover rate than”); and
(b) quantifying, in the processed sample, a phospho-tau value and an Aβ 42/40 value, wherein a significantly different phospho-tau value and/or Aβ 42/40 value discriminates a tauopathy from a healthy state (see [0010] “In another aspect, the present disclosure encompasses a method to stage a subject after onset of Alzheimer’s disease (AD) symptoms. The method comprises (a) providing an isolated tau sample obtained from a subject and measuring, in the isolated tau sample, tau phosphorylation at one or more amino acid residue chosen from T181 , T205 and T217 and optionally measuring total tau; and (b) diagnosing the subject as being a certain number of years after onset of MCI due to AD when the measured phosphorylation level(s) significantly deviate from the mean in a control population without brain amyloid plaques as measured by PET imaging and/or Ab42/40 measurement in CSF. Alternatively, or in addition to, using a measurement of tau phosphorylation at T181, T205 and/or T217, optionally with a measurement of total tau, a ratio calculated from the measured phosphorylation level(s), or a ratio calculated from the measured phosphorylation level(s) and total tau, may be used. A ratio calculated from the measured phosphorylation level(s) may be a ratio between p-T181 and p-T205, p-T217 and p-T205, or p-T181 and p-T217. A ratio calculated from the measured phosphorylation level(s) and total tau may be a ratio between p-T181 and total tau, p-T205 and total tau, or p-T217 and total tau. Mathematical operations other than a ratio may also be used.”, see [0271] “This profile allows the discrimination of AD versus non-AD pathologies and the detection of AD process many years prior to cognitive symptoms or complaint.”).
Regarding claim 70, Barthelemy teaches quantifying in a processed sample, a pT217/T217 value and an Ap 42/40 value (see [0008] “…(a) providing an isolated tau sample obtained from a subject and measuring, in the isolated tau sample, tau phosphorylation at one or more amino acid residue chosen from T181, T205 and T217 and optionally measuring total tau; and (b) diagnosing the subject as having an increased risk for conversion to MCI due to AD when the measured phosphorylation level(s) significantly deviate from the mean in a control population without brain amyloid plaques as measured by PET imaging and/or Ab42/40 measurement in CSF.”).
Regarding claim 73, Barthelemy teaches determining a composite pT217/T217 x Ap 42/40 value wherein an increased composite value relative to a healthy control population indicates the subject as having or at an increased risk for AD or a non-AD tauopathy (see [0008] – [0009], see [0070]).
Regarding claims 75, 78, 81, 84, and 86, Barthelemy teaches quantifying p tau 181, 153, 111, 205, and ps208 (see figure 13, see figure 15, see [0064] “Methods of the present disclosure provide means to measure the stoichiometry of phosphorylation at one or more specific amino acids of tau. In some embodiments, methods herein comprise measuring tau phosphorylation at one or more residue chosen from T111, S113, T181, S199, S202, S208, T153, T175, T205, S214, T217, and T231. In some embodiments, methods herein comprise measuring tau phosphorylation at one or more residue chosen from T111, T181, T205, S208, S214, T217, and T231”, see [0070] “(a) providing an isolated tau sample obtained from a subject and measuring, in the isolated tau sample, tau phosphorylation at one or more amino acid residue chosen from chosen from T111, S113, T181, S199, S202, S208, T153, T175, T205, S214, T217, and T231 , and optionally measuring total tau… (a) providing a first and a second isolated tau sample obtained from a subject and measuring, in each isolated tau sample, tau phosphorylation at one or more amino acid residue chosen from chosen from T111, S113, T181, S199, S202, S208, T153, T175, T205, S214, T217, and T231 , and optionally measuring total tau…”).
Regarding claim 79, Barthelemy teaches wherein the subject is diagnosed as having or at an increased risk of having AD when the detected pT153/T153 value is increased relative to a healthy control population and/or a non-AD tauopathy population (see [0072] teaching measuring pT153/T153 in those who have AD. See [0057] teaching that “significantly deviate from the mean” refers to at least 1 standard deviation above or below the mean. See [0131] teaching that pT153 was not detected in non-AD patients and is likely increased in AD patients. See [0143] teaching that pT153 was exclusively found in AD CSF).
Regarding claim 82, Barthelemy teaches wherein the subject is diagnosed as having or at an increased risk of having AD when the detected pT111/T111 value is increased relative to a healthy control population and/or a non-AD tauopathy population (see [0025], see figure 11, see [0071] teaching measuring T111 in order to diagnose AD staging and where the pT111 levels are significantly deviated from the mean of the control population. See [0057] teaching that “significantly deviate from the mean” refers to at least 1 standard deviation above or below the mean.)
Regarding claim 85, Barthelemy teaches wherein the subject is diagnosed as having or at an increased risk of having a tauopathy when the detected pT205/T205 value is increased relative to a healthy control population (see [0032] teaching an increase in pT205 levels. See [0282] teaching an increase in T205 levels in subject with AD). Regarding claim 87, Barthelemy teaches wherein the subject is diagnosed as having or at an increased risk of having a tauopathy when the detected pS208/S208 value is increased relative to a healthy control population (see [0023] teaching pS208 levels are increased in those who have AD. See [0072] that teaches measuring pS208/S208 to diagnose AD staging and where pS208 levels and where pS208 levels are significantly deviated from the mean of the control population. See [0057] teaching that “significantly deviate from the mean” refers to at least 1 standard deviation above or below the mean.)
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.
2.Claim 74 and 76-77 are rejected under 35 U.S.C. 103 as being unpatentable over Barthelemy et al., (WO 2019213612A1) as discussed above in the 35 USC 102 rejection.
Regarding claims 74 and 76, Barthelemy teaches possible specific p-tau profiles that are found in frontotemporal dementia (FTD) patients (see [0005], see [0056], see [01436]). Further, Barthelemy teaches decreasing p-T217 and p-T181 levels is associated with dementia and cognitive decline patients (see [0033], see figures 19A-19D). Barthelemy teaches determining a composite pT217/T217 x Ap 42/40 value wherein an increased composite value relative to a healthy control population indicates the subject as having or at an increased risk for AD or a non-AD tauopathy (see [0008] – [0009], see [0070]). While Barthelemy doesn’t explicitly teach diagnosing FTD when levels of p-T217 or p-T181 are decreased, but it would have been prima facia obvious to one of ordinary skill in the art at the time of the instant application to consider measuring p-T217 and/or p-T181 to determine if someone has or is at risk for having FTD, because as Barthelemy teaches, p-T217 and/or p-T181 levels are decreased in those who have dementia or cognitive decline. One of ordinary skill in the art would have considered comparing the levels of the biomarkers from the subject to a healthy control to determine if the levels have increased, decreased, or stayed the same. Using a healthy control sample when measuring biomarkers to compare values is a commonly used technique in the art.
Regarding claim 77, Barthelemy teaches a method of staging a subject after onset of Alzheimer’s disease (AD) by measuring p-T181/T181 levels and diagnosing a subject being a certain number of years after onset of MCI due to AD when the phosphorylation levels significantly deviate from the mean in a control population without brain amyloid plaques (see [0010]). Barthelemy further teaches a profile that allows the discrimination of AD versus non-AD pathologies (see [0271]). While Barthelemy does not explicitly teach excluding a subject from an AD diagnosis when the detected pT181/T181 value is decreased relative to an AD population, it would have been prima facia obvious to one of ordinary skill in the art at the time of the instant application to measure pT181/T181 levels in a subject who is suspected of having AD because as Barthelemy teaches, pT181/T181 is a known biomarker for AD (see [0010]). One of ordinary skill in the art would have considered comparing the biomarker levels from the subject to a control (AD population) in order to discriminate AD and non-AD (see [0271]). It is a common technique in the diagnostic art to compare biomarker levels to a control population in order to differentiate/discriminate between diseases. It would have been prima facia obvious to one of ordinary skill in the art to exclude a subject from an AD diagnosis when they do not have the biomarker levels that are associated with AD disease.
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678