DETAILED ACTION
Claims 17-36 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 09/29/2023 has been considered by the examiner.
Claim Objections
Claim 32 is objected to because of the following informalities: The claim recites an abbreviation and/or acronym of “STED”, “SIM”, “STORM”, and “dSTORM”, 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.
Claim 32 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 32 recites “wherein detection is carried out by one of confocal fluorescent microscopy, fluorescence correlation spectroscopy (FCS), optionally in combination with cross correlation and single particle immunosolvent laser scanning assay, laser scanning microscopy (LSM) or TIRF microscopy, as well as a corresponding super-resolution variant STED, SIM, STORM, or dSTORM”.
Claim 32 is indefinite because it is unclear from the language of “optionally in combination with…as well as” whether a corresponding super-resolution variant STED, SIM, STORM, or dSTORM is optional or not. Thus, it is unknown what the claim limitations require and what is optional.
The claim should recite proper Markush language i.e., “wherein detection is carried out by one or more selected from a group consisting of confocal fluorescent microscopy, fluorescence correlation spectroscopy (FCS), cross correlation and single particle immunosolvent laser scanning assay, laser scanning microscopy (LSM) or TIRF microscopy, corresponding super-resolution variant STED, SIM, STORM, and dSTORM”.
In order to expedite prosecution, the claim is interpreted at least any one of listed methods-fluorescent microscopy, fluorescence correlation spectroscopy (FCS), cross correlation and single particle immunosolvent laser scanning assay, laser scanning microscopy (LSM) or TIRF microscopy, corresponding super-resolution variant STED, SIM, STORM, and dSTORM must be used.
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 35-36 are rejected under 35 U.S.C. 101 because the claimed methods are directed to a judicial exception (i.e., a law under 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.
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 Appendix 1 to the October 2019 Update: Subject Matter Eligibility Life Sciences & Data Processing Examples 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).
Instant claim 35 recites a method with active step of applying stool sample, adding probes to A beta and alpha synuclein and detecting aggregates and measuring Aβ and/or α-synucleins aggregates in a stool sample and correlating that measurement to the efficacy of a treatment of Alzheimer’s Disease or Parkinson’s Disease. Like claim 1 in Example 43, claim 35 is directed to at least one statutory category of invention (STEP 1: YES).
Instant claim 36 recites a method with active steps of carrying out the quantification and/or characterization of Aβ aggregates according to the method of claim 17, and comparing the measured value with a threshold. Like claim 1 in Example 43, claim 36 is directed to at least one statutory category of invention (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) and the October 2019 Update, a claim “recites” a
judicial exception when the judicial exception is “set forth” or “described” in the claim.
Regarding claim 1 in Example 43 Appendix 1 to the October 2019 Update: Subject Matter Eligibility Life Sciences & Data Processing Examples and 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.
instant claims 35-36 follows a similar fact pattern as Example 43 of the Appendix 1 to the October 2019 Update: Subject Matter Eligibility Life Sciences & Data Processing Examples.
Regarding claim 1 in Example 43 of the Appendix 1 to the October 2019 Update: Subject Matter Eligibility Life Sciences & Data Processing Examples and 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.
Limitation (a) in claim 1 of Example 43 of the “2019 PEG” 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. However, the claim still must be reviewed to determine if it recites any other type of judicial exception.
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. Not 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.
Similarly, instant claim 35 recites the use of several nature-based product limitations including Aβ and α- synuclein. 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 35 does not invoke this exception because review of this claim indicates that it is focused on a process of determining how much Aβ and/or α- synuclein 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. However, the claim still must be reviewed to determine if it recites any other type of judicial exception.
Further, instant claim 35 recites a judicial exception of “comparing the active ingredients and/or curative methods with respect to their effect on Aβ or α- synuclein aggregate formation, those active ingredients and/or curative methods which show lower Aβ or α-synuclein aggregate formation compared to a control being selected.” The language of “comparing” is directed to a judicial exception as it is 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 35 recites the judicial exception of applying and using an abstract idea.
Instant claim 36 also recites the judicial exception of “A method for making a decision regarding the inclusion of an individual in a clinical trial or test, wherein the method comprises carrying out a quantification and/or characterization of A-beta aggregates according to the method of claim 17 and comparing a measured value with a threshold value.” The language of “making a decision” and “comparing” is directed to a judicial exception as it is 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 36 recites the judicial exception of applying and using an abstract idea.
Accordingly, instant claim 35 and instant claim 36 recite a judicial exception (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?
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 35 does not have additional elements that would integrate the judicial exception cited above into a practical application. Claim 1 of Example 43 recites the use of a general treatment. It is recited at the highest level of generality. This limitation indicates that a treatment is to be administered, but it does not provide any information as to how the patient is to be treated, or what the treatment is. Thus, the limitation of treating a subject fails to meaningfully limit the claim because it does not require any particular application and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Unlike claim 1 of Example 43, instant claim 35 does not recite any active steps in treating. Instant claim 35 simply just recites treatment in the preamble and provides no active steps. “Treatment” in the preamble fails to meaningfully limit the claim to any particular application. Claim 1 of Example 43 failed with an active step, instant claim 35 does not even recite an active step for treatment.
Therefore, instant claim 35 does not integrate the judicial exception into a practical application.
Instant claim 36 does not have additional elements that would integrate the judicial exception into a practical application. In comparison to claim 1 of Example 43, Example 43 did not pass step 2A prong 2 with a step of general treatment, instant claim 36 does not even recite any steps of treatment. Example 43 failed with a step of a general treatment, instant claim 36 does not have an active step, let alone a step for treatment. Instant claim 36 does not recite any additional elements other than the abstract idea. Instant claim 36 recites the judicial exception without any active steps, therefore, instant claim 36 does not integrate the judicial exception into a practical application because they do not amount to more than the judicial exception themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d). Instant claim 36 recites “making a decision” and “comparing the measured value with a threshold value” which falls within an abstract idea as it can practically be performed in the mind.
Therefore, instant claim 36 does not integrate the judicial exception into a practical application.
Step 2B: Does this claim recite significantly more?
Regarding instant claims 35-36, 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.
Regarding instant claim 35, Even though the claim does recites “treating” a subject in the preamble, the claim does not recite any active steps in “treating”. Instant claim 35 simply recites “treating” in the preamble and the recitation of “treatment” in the preamble is drawn to an intended use and does not impart meaningfully limit the claim to any particular application. Instant claim 35 recites “comparing” and “compared”, which is directed to a judicial exception as abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion)).
Accordingly, instant claim 35 is not eligible (STEP 2B: NO).
Regarding instant claim 36, As explained with respect to Step 2A Prong Two, the claim does not recite any active steps. The only steps claim 36 recites are steps that can be performed in the mind such as “making a decision” and “comparing”, which are directed to a judicial exception (an abstract idea). Further, instant claim 35 recites “making a decision” in the preamble and the recitation of “making a decision” in the preamble fails to meaningfully limit the claim to any particular application.
Accordingly, instant claim 36 is not eligible (STEP 2B: NO).
Thus, instant claims 35-36 are rejected under 35 USC 101.
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.
Claims 17-36 are rejected under 35 U.S.C. 103 as being unpatentable over Willbold et al., (US20150024512A1) (IDS filed on 09/29/2023), in view of Pellegrini et al., “Prodromal Intestinal Events in Alzheimer's Disease (AD): Colonic Dysmotility and Inflammation Are Associated with Enteric AD-Related Protein Deposition.” International journal of molecular sciences vol. 21,10 3523. 15 May. 2020, doi:10.3390/ijms21103523 (IDS filed on 09/29/2023).
Willbold teaches a method of measuring Aβ aggregates in a sample comprising (a) providing a substrate on which capture molecules are immobilized, (b) applying a stool sample to be tested to the substrate, (c) adding probes labelled for detection, which by specific binding to A-beta or alpha-synuclein aggregates mark these, and (d) detection of the marked aggregates by high spatial resolution, specifically, confocal fluorescence microscopy, fluorescence correlation spectroscopy (FCS), optionally in combination with cross-correlation and single particle immunosolvent laser scanning assay, laser scanning microscopy (LSM), Wetfeld microscopy, TIRF microscopy, and the corresponding super resolution modifications STED, SIM, STORM and dSTORM (see reference claim 28 and 43-44) (instant ref. claims 17 and 31-32). Willbold teaches a glass substrate that has a hydrophilic coating of dextran (see claims 31-33) (instant claims 20-21), where the capture molecules are anti Aβ aggregates that specifically bind an epitope of the Aβ aggregates, are labeled with fluorescent dyes and are covalently bound to the substrate (see reference claims 34-37) (instant ref. claims 22-25).
Willbold teaches the use of two or more different Aβ peptide-specific probes that are fluorescently dyed and specifically bind to the N-terminal epitope of Aβ peptide (see reference claims 38-42) (instant ref. claims 26-30). Willbold teaches using an internal or external standard to quantify Aβ aggregates and the standard for quantification is a polymer composed of polypeptide sequences which with respect to their sequence are identical to that subregion of the endogenous proteins which forms an epitope or have a homology of at least 50% over the corresponding subregion with those endogenous proteins which cause a protein aggregation disease or an amyloid degeneration or protein misfolding disease, and wherein the polymers do not aggregate and the polypeptide sequence has a biological activity of the epitope (see reference claims 48-49) (instant ref. claims 33-34).
Willbold further teaches a method for determining the efficacy of active ingredients and/or curative methods for the treatment of Alzheimer's disease or Parkinson's disease, wherein the method comprises carrying out the method of claim 17 and comparing the active ingredients and/or curative methods with respect to their effect on A-beta or alpha- synuclein aggregate formation, those active ingredients and/or curative methods which show lower A-beta or alpha-synuclein aggregate formation compared to a control being selected (see claim 51) (instant claim 35).
Lastly, Willbold teaches a method for making a decision regarding the inclusion of an individual in a clinical trial or test, wherein the method comprises carrying out a quantification and/or characterization of A-beta aggregates according to the method of claim 17 and comparing a measured value with a threshold value (see claim 52) (instant claim 36).
Willbold does not teach towards the sample being a stool sample.
Pellegrini teaches using a stool sample to detect Aβ aggregates (see abstract) (instant claim 17) and the stool sample is pre-treated by homogenization and separation of solid components from liquid components of the stool sample with addition of water or one or more aqueous buffer solutions (see page 18) (instant claims 18-19).
It would have been prima facia obvious to one of ordinary skill in the art before the instant application to combine the method of selective quantification of Aβ aggregates as taught by Willbold with the stool sample taught by Pellegrini. Pellegrini provides motivation for measuring Aβ aggregates in stool by teaching that Aβ aggregates detected in the brain can lead to Alzheimer’s Disease related protein deposits in intestinal tissues correlated with those detected in the brain at early stages of the disease (see page 13). One of ordinary skill in the art would have been motivated to use Willbold’s methods of quantification of Aβ aggregates with Pellegrini’s teaching of using stool to detect Aβ aggregates because as Pellegrini teaches, Aβ aggregates have been shown to be detectable in stool at early stages of the disease. The artisan would have reasonable expectation of success based on the cumulative disclosures of these prior art references.
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