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 .
DETAILED ACTION
Status of Claims
1. Claims 1, 3-10, 19, 27, 29-35, and 37-40 are pending and are under examination.
Priority
2. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 National Stage application of PCT/US2022/018067 filed 02/28/2022, which claims the benefit of Provisional Application Number 63/157,896 filed 03/08/2021. Based on the filing receipt, the effective filing date of this application is March 8, 2021 which is the filing date of Provisional Application Number 63/157,896 from which the benefit of domestic priority is claimed.
Claim Objections
3. Claim 37 is objected to in depending from a cancelled claim. See also claim 38. 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.
4. Claims 1, 3-10, 19, 27, 29-35, and 37-40 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.
Claim 1 is vague and indefinite in reciting “receiving results of a protein assay relating to the expression of a panel of proteins” in step (i) because it appears to recite a mental step. In particular, it is unclear how “receiving results of a protein assay” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “results” that “relate” to the expression of the proteins because “results” and “relating” are subjective terms lacking a comparative basis for defining their metes and bounds. Does Applicant simply intend “presence” of expression or “amount” of expression?
Claim 1 is vague and indefinite in reciting “determining that the expression of at least one of the members of the panel of proteins is increased … compared to the expression of the at least one member in a reference sample” in step (ii) because it appears to recite a mental step. In particular, it is unclear how “determining … the expression … of the panel of proteins is increased in the biological sample compared to the expression … in a reference sample” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “reference sample” relative to “increase in the biological sample” because “reference” is a subjective term lacking a comparative basis for defining its metes and bounds. Does Applicant perhaps intend a “normal” control reference sample?
Claim 6 is also vague and indefinite in reciting “a step of selecting the subject based on the presence or expression level of apolipoprotein E isoform 4 (apoE4) and/or 14-3-3 protein zeta/delta (YWHAZ)” because it appears to recite a mental step. In particular, it is unclear how “selecting the subject based on expression … of the panel of proteins” encompasses a positive laboratory method step.
Claim 6 is ambiguous in reciting “a step of selecting the subject based on the presence or expression level of apolipoprotein E isoform 4 (apoE4) and/or 14-3-3 protein zeta/delta (YWHAZ)” because it is unclear what the subject is being selected for in relation to the method steps in claim 1 from which it depends and on what basis with respect to the expression level (i.e. increased, decreased) of ApoE4 and/or YWHAZ.
Claim 10 is vague and indefinite in reciting “receiving results of a protein assay relating to the expression of each member of a panel of proteins” in step (i) because it appears to recite a mental step. In particular, it is unclear how “receiving results of a protein assay” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “results” that “relate” to the expression of the proteins because “results” and “relating” are subjective terms lacking a comparative basis for defining their metes and bounds. Does Applicant simply intend “presence” of expression or “amount” of expression?
Claim 10 is vague and indefinite in reciting “determining that the expression of at least one of the members of the panel of proteins is increased … compared to the expression level of the at least one member in a reference sample” in step (ii) because it appears to recite a mental step. In particular, it is unclear how “determining … the expression … of the panel of proteins is increased in the biological sample compared to the expression … in a reference sample” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “reference sample” relative to “increase in the biological sample” because “reference” is a subjective term lacking a comparative basis for defining its metes and bounds. Does Applicant perhaps intend a “normal” control reference sample?
Claim 19 is vague and indefinite in reciting “receiving results of a protein assay relating to the expression of each member of a panel of proteins” in step (i) because it appears to recite a mental step. In particular, it is unclear how “receiving results of a protein assay” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “results” that “relate” to the expression of the proteins because “results” and “relating” are subjective terms lacking a comparative basis for defining their metes and bounds. Does Applicant simply intend “presence” of expression or “amount” of expression?
Claim 19 is vague and indefinite in reciting “determining that the expression of at least one of the members of the panel of proteins is increased … compared to the expression level of the at least one member in a reference sample” in step (ii) because it appears to recite a mental step. In particular, it is unclear how “determining … the expression … of the panel of proteins is increased in the biological sample compared to the expression … in a reference sample” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “reference sample” relative to “increase in the biological sample” because “reference” is a subjective term lacking a comparative basis for defining its metes and bounds. Does Applicant perhaps intend a “normal” control reference sample?
Claim 27 is vague and indefinite in reciting “receiving results of a protein assay relating to the expression of each member of a panel of proteins” in step (i) because it appears to recite a mental step. In particular, it is unclear how “receiving results of a protein assay” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “results” that “relate” to the expression of the proteins because “results” and “relating” are subjective terms lacking a comparative basis for defining their metes and bounds. Does Applicant simply intend “presence” of expression or “amount” of expression?
Claim 27 is vague and indefinite in reciting “determining that the expression of at least one of the members of the panel of proteins is increased … compared to the expression level of the at least one member in a reference sample” in step (ii) because it appears to recite a mental step. In particular, it is unclear how “determining … the expression … of the panel of proteins is increased in the biological sample compared to the expression … in a reference sample” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “reference sample” relative to “increase in the biological sample” because “reference” is a subjective term lacking a comparative basis for defining its metes and bounds. Does Applicant perhaps intend a “normal” control reference sample?
Claim 35 is vague and indefinite in reciting “receiving results of a protein assay relating to the expression of each member of a panel of proteins” in step (i) because it appears to recite a mental step. In particular, it is unclear how “receiving results of a protein assay” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “results” that “relate” to the expression of the proteins because “results” and “relating” are subjective terms lacking a comparative basis for defining their metes and bounds. Does Applicant simply intend “presence” of expression or “amount” of expression?
Claim 35 is vague and indefinite in reciting “determining that the expression of at least one of the members of the panel of proteins is increased … compared to the expression level of the at least one member in a reference sample” in step (ii) because it appears to recite a mental step. In particular, it is unclear how “determining … the expression … of the panel of proteins is increased in the biological sample compared to the expression … in a reference sample” encompasses a positive laboratory method step. It is further unclear what is encompassed in the recitation of “reference sample” relative to “increase in the biological sample” because “reference” is a subjective term lacking a comparative basis for defining its metes and bounds. Does Applicant perhaps intend a “normal” control reference sample?
Claim 37 is vague and indefinite in reciting “the subject is selected for participation in a clinical trial” because it is unclear how the subject is selected for participation and on what basis.
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.
5. Claims 1, 3-10, 19, 27, 29-35, and 37-40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Based upon an analysis with respect to each of these claims as a whole, these claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The claims recite a correlation between an increased level of any one or more of pyruvate kinase (PKM), fructose bisphosphate aldolase A (ALDOA), lactate dehydrogenase B (LDHB, LDH-H, LDH heart type), apolipoprotein E isoform 4 (ApoE4, Apo-E4) and 14-3-3 protein zeta/delta (YWHAZ) protein biomarkers and the diagnostic presence of Alzheimer’s Disease (AD) that is deemed to require administration of treatment of AD to the subject. This judicial exception is not integrated into a practical application because the claimed invention is limited to a correlation being categorized as a law of nature/natural phenomenon or existence in nature apart from any human action without significantly more. The claims do not include additional elements that are sufficient to amount to significantly more because the judicial exception is not integrated into a significant practical application in a manner that imposes a meaningful limit on the judicial exception. This new consideration is based on case law including Vanda, for evaluation of particular treatment or prophylaxis limitations.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A Prong One
Claims 1, 6, 10, 19, 27, 35, and 40 recite a correlation between an increased level of at least one of PKM, ALDOA, LDHB biomarkers – the assay results obtained or received as a panel of three proteins (claim 1, claim 35, claim 40), and also ApoE4 and/or YWHAZ protein biomarkers– the assay results obtained or received as a panel of four proteins (claims 1 and claim 6; claim 10; claim 19, claim 35, claim 40); the assay results obtained or received as a panel of five proteins (claim 27, claim 35, claim 40); wherein an increased level of the at least one of the protein biomarkers being correlated to the diagnostic presence of AD is deemed to require administration of treatment of AD to the subject.
The claimed steps of “determining that the expression of at least one of the protein members of the panel is increased” in the sample from the subject as compared to a normal reference sample (diagnostic step) read on mental processes, such as a physician receiving data result from a patient, evaluating, and forming an observation/evaluation/judgment/opinion regarding the subject’s likely diagnosis or prognosis of the disease. See the 2019 Revised Patent Subject Matter Eligibility Guidance (“2019 PEG”), issued on 1/7/2019 and available at https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf. Such steps of comparing biomarker levels or measurements to a reference reads on mental processes insofar as such comparison of information could take place wholly in the human mind, or by a human using pen and paper. Similar mental processes have been held by the courts to be abstract ideas, e.g., collecting and comparing known information in Classen, or comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC. Such concepts as assessing abnormal aberrant or increased results and conditions by performing protein assays for biomarkers, determining abnormal elevated biomarker levels, and forming decisions about the results have also been characterized by the courts as abstract ideas.
Additionally, the correlation between upregulation of at least one or more of PKM, ALDOA, LDHB, ApoE4, and YWHAZ protein biomarkers and the diagnostic presence of AD is further categorized as a law of nature/natural phenomenon which is a judicial exception because the correlation exists in nature apart from any human action (July 2015 Update, Quick Reference Sheet; see also Univ. of Utah Research Found. v. Ambry Genetics Corp., 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)). As set forth supra, the judicial exception recited is not integrated into a practical application because steps corresponding to mental activity, which could be performed in a practitioner’s head, are insufficient to constitute a practical application.
Step 2A Prong Two
“Integration into a practical application” requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception; evaluating whether any additional element is recited beyond the judicial exception; and determining whether the additional element(s) integrate the exception into a practical application of the exception. This new consideration is based on case law including Vanda, for evaluation of particular treatment or prophylaxis limitations.
With respect to claims 1, 10, 19, 27, and 35, this judicial exception is not integrated into a practical application because steps corresponding to mental activity, which could be performed in a practitioner’s head, are insufficient to constitute a practical application. In this case, determining the diagnostic presence of AD, without significantly more, is a judicial exception and not a practical application thereof.
With respect to the recitation of “administering a treatment for AD to the subject, to thereby treat AD in the subject” in claims 1, 10, 19, 27, and 35 wherein a post-treatment “reduces or alleviates one or more symptoms of AD in the subject” encompasses additional steps/ elements that are also insufficient to render the claims patent-eligible because simply appending with a generic treatment, which in this case indicates treatment efficacy, specified at a high level of generality, has been held not to be enough to qualify as "significantly more" when recited in a claim with a judicial exception. Still, there are no subsequent steps recited that would practically apply the method depending on the results of the method, i.e. process steps that integrate the natural principle into the method and assure that it is applied in some practical manner.
It is also noted that the claims do not clearly recite or require any physical or wet laboratory steps to be performed, such as performing immunological assays to measure PKM, ALDOA, LDHB, ApoE4, and YWHAZ protein biomarkers; and recite only obtaining a biological sample from the subject in claim 5 and that the biological sample is CSF, or whole blood in claims 3 and 29. Steps of “determining … the expression of at least one of the members of the panel or proteins given their broadest reasonable interpretation, read on reading numerical assay results off of a chart, which basically constitutes mental activity.
Although claims 4 and 30 do suggest invoking steps incorporated into assay techniques or processes such as ELISA, MS, western blot, this is not a practical application of the judicial exception because such steps are merely data gathering steps using conventionally known techniques. These assay methods are recited at a high level of generality and are not tied, for example, to a particular novel machine or apparatus. Accordingly, even if the claims are interpreted as requiring wet laboratory assay steps to obtain a measure of the panel of protein biomarkers, such steps are insufficient because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015).
As above, there are no subsequent steps recited in claims 1, 10, 19, 27, and 35 that would practically apply the methods depending on the results of the method, i.e. process steps that integrate the natural principle into the method and assure that it is applied in some practical manner.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Step 2B
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
As stated supra, assay methods or techniques that gather data are recited at a high level of generality and are not limited, for example, to any specific or unconventional testing technique. Limitations that are necessary for all practical applications of a judicial exception, such that everyone practicing the judicial exception would be required to perform those steps or every product embodying that judicial exception would be required to include those features, would not be sufficient to confer patent eligibility. Such additional claim limitations are insufficient to render the claims patent-eligible because simply appending well-understood, routine and conventional techniques previously known to the industry, specified at a high level of generality, has been held not to be enough to qualify as "significantly more" when recited in a claim with a judicial exception.
Claims 4 and 30 specify certain protein assay processes or techniques such as ELISA, mass spectrometry, western blot, and nanoscale needle biosensor assay which were well-known, routine and conventional as evidenced in the Applicant’s disclosure in paragraphs [0076-0086] of the specification, which states that such assay processes were “known to those of skill in the art“ alongside a long list of well-known applicable technologies and kits therefor, which are widely “commercially available”.
Therefore, prior to the effective filing date of the claimed invention, it was well-understood, routine and conventional to detect and measure protein biomarkers such as ApoE, PKM, ALDOA, LDHB, and YWHAZ in CSF using assay technologies recited in claims 4 and 30. See also Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). “Where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent eligible subject matter if the methods themselves are conventional, routine and well understood applications in the art.”
When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in such steps that distinguishes them from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting a protein using an antibody to that protein. See also MPEP 2106.05(g). Further, it is well established that the mere physical or tangible nature of additional elements such as the receiving and determining steps does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)).
The combination of steps recited in these process claims taken as a whole, including the well-understood, routine, and conventional steps of data acquisition recited with a high level of generality which would substantially foreclose others from using the naturally occurring correlation, or limitations of the use to a particular technological environment (field-of-use) (“Guidance”, I.B.1), are not sufficient to qualify as a patent-eligible practical application of a law of nature or of a naturally occurring correlation, i.e. of a natural principle, as the claims do not amount to significantly more than a statement of the natural principle with generalized directions to apply it to the relevant population. See Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S.Ct. 1289, 101 USPQ2d 1961 (2012).
Based upon this analysis of the claims as a whole, the claims do not recite something significantly different than a judicial exception and fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
6. Claims 1, 3-9, 19, 35, and 37-40 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kohli et al. (US 2010/0169988 A1).
Kohli et al. disclose a method for determining neurodegenerative disorder-associated protein (APP: amyloid precursor protein) expression that determines presence or indication of Alzheimer's disease (AD) in a subject and treating AD in the subject (Abstract). Kohli et al. specifically teach that the neurodegenerative disorder-associated proteins are enzymes that can be detected in cerebrospinal fluid (CSF) of the central nervous system of the subject [0154, 0175, 0181, 0182].
Kohli et al. teach (i) receiving results of protein assay showing expression levels of a panel of proteins (drug targets, enzymes) comprising pyruvate kinase (PKM), fructose bisphosphate aldolase A (ALDOA), and lactate dehydrogenase B chain (LDHB) in the CSF of the subject ([0175, 0181, 0182]; Table 5); (ii) determining an increased expression level (upregulation) of at least one of the proteins in the panel as compared to the expression level of the protein in a normal control reference sample that provides indication of AD in the subject so as to require administration of treatment ([0175, 0182, 0248]; Table 5); and (iii) administering treatment for AD to the subject based on the increased expression level of at least one protein determined in (ii), thereby treating AD in the subject [0248, 0300]. Kohli et al. teach repeating assay steps (monitoring) including (i) and (ii) at a later time point after treatment of the subject has been initiated to monitor efficacy of the treatment [0240].
Kohli et al. also teach that the panel may comprise apolipoprotein E isoform 4 (apoE4) [0248]. The protein assay is performed using mass spectrometry (MS), specifically matrix-assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF) [0180]. Kohli et al. also teach that the treatment for AD comprises a cholinesterase inhibitor or memantine [0300]. The treatment reduces or alleviates one or more symptoms of AD in the subject, wherein the one or more symptoms of AD comprise: impaired cognitive function, worsening cognitive function, episodes of forgetting (failing memory), confusion, disorientation, agitation, impaired ability to form new memories, anger or combinations thereof [0246, 0247].
Accordingly, Kohli et al. appears to read on Applicant’s claimed invention.
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.
7. Claims 1, 3-10, 19, 27, 29-32, 34, 35, and 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Bader et al. (Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease. Molecular Systems Biology 16:6 e9356 (2020) IDS) in view of Kohli et al. (US 2010/0169988 A1).
Bader et al. disclose a method for indicating the presence of Alzheimer's disease (AD) in a population of subjects. The method comprises: (i) receiving results of a protein assay showing expression levels of a panel of 40 protein biomarkers including glycolytic proteins comprising pyruvate kinase (PKM1, PKM2), fructose bisphosphate aldolase A (ALDOA), lactate dehydrogenase B chain (LDHB), and 14-3-3 protein zeta/delta (YWHAZ) in a biological sample from the subjects; wherein the biological sample is cerebrospinal fluid (CSF) (p. 2, left col. 2nd & 3rd full ¶s; p. 3; p. 4, right col. 4th full ¶ to p. 5; p. 11, right col.; especially p. 8, left col. last ¶ to p. 9; Figure 1C; Figure 3F); and (ii) determining an increased expression level (up-regulation) of at least one of the proteins in the panel as compared to the expression level of the protein in a normal (non-AD) control reference samples to provide indication of the presence of AD in the subjects (p. 4, right col. 4th full ¶ to p. 5; p. 6; especially p. 8, left col. last ¶ to p. 9; Figure 3F; Figure 4D; Figure 4G; Figure 4H). Bader et al. showed that all of PKM, ALDOA, LDHB, and yWHAZ are increased or up-regulated in all of the AD subjects (p. 8, left col. last ¶ to p. 9; Figure 3F; Figure 4D; Figure 4G; Figure 4H). Bader et al. teach repeating assay steps including (i) and (ii) (monitoring) at a later time point including after treatment of the AD subjects (p. 4, right col. 4th full ¶ to p. 5). The protein assay is performed using mass spectrometry (LC-MS-MS) (p. 2, left col. 2nd & 3rd full ¶s; p. 13, left col.; Figure 1).
Bader et al. teach selecting subjects with or without AD; and selection is also based on the presence or expression of YWHAZ; wherein the subjects are selected for participation in a clinical trial for AD agent in an early-stage intervention for AD (p. 2, left col. 1st full ¶; p. 11, left col.; Figure 1; Figure 3F; Figure 4D; Figure 4G; Figure 4H). One or more symptoms of AD comprise: impaired cognitive function, worsening cognitive function, confusion, disorientation, difficulty concentrating (difficulty performing daily activities), and impaired ability to form new memories (memory impairment) (p. 1, right col.).
Bader et al. differ from the instant invention in failing to teach (iii) administering a treatment for AD to the subject based on an increase in the expression of assay results determined in (ii). Bader further does not teach a panel comprising all of five protein biomarkers including apolipoprotein E isoform 4 (apoE4).
Kohli et al. is discussed supra.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the AD treatment step taught by Kohli into the proteome profiling method taught by Bader because Bader taught that a panel of specific protein biomarkers including PKM, ALDOA, LDHB, and YWHAZ show significant up-regulation in CSF samples of AD subjects and Kohli taught that increased levels of specific protein biomarkers of AD including PKM, ALDOA, LDHB that indicate the presence of AD provides indication of the need to administer treatment of AD to the subject. One of ordinary skill would have been motivated to incorporate the teaching of Kohli into the method of Bader because both of Bader and Kohli recognize the significance of individualized diagnosis and treatment of AD in a subject.
8. Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Kohli et al. (US 2010/0169988 A1) in view of Carney et al. (Comparison of cholinesterase inhibitor safety in real-world practice. Alzheimer’s and Dementia: Translational Research & Clinical Interventions 5: 732-739 (2019)).
Kohli et al. is discussed supra. Kohli et al. differ from the instant invention in failing to teach that the cholinesterase inhibitor is donezepil, galantamine, and rivastigmine.
Carney et al. teach that cholinesterase inhibitors (ChEIs) are widely used to treat mild to moderate Alzheimer's disease (AD) and related dementia. These ChEIs comprise donezepil, galantamine, and rivastigmine. Through inhibition of acetylcholinesterase, these ChEIs allow acetylcholine to accumulate; wherein increased acetylcholine levels allows increase of neuronal activity; thereby, reducing or alleviating one or more symptoms of AD in a subject.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have incorporated the teaching of Carney on the efficacy of donezepil, galantamine, and rivastigmine as ChEIs into the method of diagnosing and treating AD as taught by Kohli because Carney taught that donezepil, galantamine, and rivastigmine can have distinct benefits and adverse disadvantages in their usage. One of ordinary skill would have been motivated to have incorporated the teaching of Carney into the diagnostic and treatment method for AD as taught by Kohli because Carney has shown the advantage of clinically meaningful benefits of individualized ChEI therapy in AD subjects.
9. No claims are allowed.
Remarks
10. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Maniv et al. (US 2022/0365073 A1) teach systems and methods for in vitro modeling of neurodegenerative diseases.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
June 10, 2026
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