DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Election/Restrictions
Applicant’s election without traverse of Group II (Claims 1, 3, and 8-9), in the reply filed on 3 November 2025, is acknowledged.
Applicants elected “b-RAF” as a species of “kinase protein”. The elected “b-RAF” kinase protein, as used in the methods of elected Group II, is free of the prior art.
The Examiner extended the Markush search to “protein kinase C (PKC)” as a species of “kinase protein”. This extended Markush search has prior art.
Therefore, per Markush search practice, the Markush search will not be extended unnecessarily to additional species of “kinase protein” within this Office Action.
The extended Markush search reads on claims 1, 3, and 8-9.
Applicants did not provide a species election of “compound” therefore, this lack of response is non-compliant. In response, the Office withdraws the Election of Species Requirement just for the species of “compound” of elected Group II. The Election of Species Requirement is maintained for “kinase protein” for elected Group II.
Claims 2 and 4-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention of Group I, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3 November 2025.
Please cancel non-elected withdrawn Group I composition claims as a non-elected/withdrawn composition Group cannot be rejoined to an elected method of use Group (here, Group II).
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Current Status of 18/113,369
This Office Action is responsive to the original claims of 23 February 2023.
Original claims 1, 3, and 8-9 have been examined on the merits.
Priority
The effective filing date is 25 December 2014.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 23 February 2023, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 1, 3, and 8-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural phenomenon and abstract ideas without significantly more. The claim(s) recite(s) diagnostic and screening methods. This judicial exception is not integrated into a practical application because there is no particular, non-conventional assay or technological improvement recited and no transformation beyond data observation. The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the rejected claims all recite screening/diagnostic processes relying on routine techniques to detect natural correlations/phenomena.
Step 1: Is the claim to a process, machine, manufacture, or composition of matter?
Yes, each of claims 1, 3, and 8-9 are directed to a process/method.
Revised Step 2A
Prong 1: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes, each of the claims 1, 3, and 8-9 recite abstract ideas and natural phenomenon.
The core of the claim 1 is a correlation between elevated kinase activity/expression and Alzheimer’s disease—this is a law of nature/natural phenomenon which is a judicial exception (JE).
For claim 3: The step of “binding” reflects a natural phenomenon (molecular interaction), and “selecting” is a mental process. Thus, each of the natural phenomenon and abstract ideas are JE. The recitation of “bringing into contact” is generic lab activity.
For claim 8: Directed to observing suppression of a natural biological activity and then performing a mental selection. The mental selection and observations are abstract ideas and natural phenomenon, and hence constitute JEs.
For claim 9: Detecting and evaluating a natural molecular interaction; selection is mental. Hence, these are natural phenomenon and abstract ideas, which are JEs.
Prong 2: Does the claim recite additional elements that integrate the JE into a practical application?
No. The recited steps of claim 1 — detecting, comparing, determining—are high-level and generic. “Comparing” and “determining” can be performed mentally. There is no particular, non-conventional assay or technological improvement recited; no transformation beyond data observation.
No. Claim 3 discloses no specified, non-conventional assay or technological improvement.
No. Claim 8 recites “the system capable of detecting” at a high level; no non-conventional technique or technological improvement is recited.
No. Claim 9 just recites routine lab activity (contacting, detecting binding) and discloses no specified, non-conventional assay or technological improvement.
Step 2B: Does the claim recite additional elements that amount to significantly more than the JE?
No, claim 1 does not recite additional elements. The detection/comparison are routine laboratory/analytical steps. Under Mayo, Cleveland Clinic, and Athena, this type of diagnostic claim is ineligible when the screening/diagnostic processes rely on routine techniques to detect natural correlations/phenomena as is the case with instant claim 1.
No, claim 3 does not recite additional elements. Nothing suggests an inventive concept beyond observing a natural interaction and making a selection. In fact, Cleveland Clinic and Athena found similar screening/diagnostic processes ineligible when they rely on routine techniques to detect natural correlations/phenomena.
No, claim 8 does not recite additional elements. Claim 8 recites routine lab detection and selection each of which do not add “significantly more”. In fact, Cleveland Clinic and Athena found similar screening/diagnostic processes ineligible when they rely on routine techniques to detect natural correlations/phenomena.
No, claim 9 does not recite additional elements. No “significantly more” than using conventional assays to observe natural phenomena and make a decision. In fact, Cleveland Clinic and Athena found similar screening/diagnostic processes ineligible when they rely on routine techniques to detect natural correlations/phenomena.
Thus, claims 1, 3, and 8-9 are not eligible subject matter and are each rejected under 35 USC 101.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over:
ALKON (WO 02/067764 A2, referenced in IDS of 23 February 2023),
in view of:
TRUITT (WO 2012/006640 A2, referenced in IDS of 23 February 2023),
in view of:
TAN (Tan, Mathew, et al. “Therapeutic effects of PKC activators in Alzheimer’s disease transgenic mice.” PNAS. (July 27, 2004), vol. 101, no. 30, pp. 11141-11146),
and in further view of:
HASEGAWA (“Microglia signaling by amyloid b protein through mitogen-activated protein kinase mediated phosphorylation of MARCKS”, NeuroReport, vol. 12, no. 11, 8 August 2001 (2001), pages 2567-2571, referenced in IDS of 23 February 2023).
The instant claims are drawn to a method of diagnosing Alzheimer’s disease by measuring the level of a protein kinase in a patient, comparing that measured level to a known control (healthy patient), and then making an Alzheimer’s disease diagnosis based on whether the measured level is higher than the known healthy control. This method requires selecting a test compound that can bind to the kinase protein of interest (claim 3) and suppressing the deleterious effect of the kinase protein.
Determining the scope and contents of the prior art:
Alkon discloses a method of diagnosing Alzheimer's disease in a patient by measuring the phosphorylation level of an indicator protein and determining if this level is abnormally elevated as compared to a basal phosphorylation protein level of non-Alzheimer’s control subject, comparing the two phosphorylation ratio and their statistical difference, and determining the presence of an elevated level as positive diagnosis for Alzheimer’s disease (Abstract; p.6, ll. 11-36). The measurement of phosphorylation may be done by an immunoassay, such as radioimmunoassay, Western blot analysis, an immunofluorescence assay, an enzyme immunoassay, an immunoprecipation assay, a chemiluminescence assay, an immunohistochemistry assay, etc. (p. 8, ll. 5-11). Such diagnostic method may comprise measuring the amount of a MAPK protein in a subject’s cells, and comparing them to the phosphorylation of a non-Alzheimer’s control subject, wherein increased phosphorylation level in the subject’s cells compared to the control cells is diagnostic of Alzheimer’s disease (p. 9, ll. 9-17).
Hasegawa discloses that amyloid b protein activates phosphorylation of MARCKS by both PKC and MAPK in microglia and may be associated with microglia activation in Alzheimer's disease (Abstract).
Truitt discloses that multiple signaling pathways converge on phosphorylating MARCKS, such as PKC isoforms and ROCK (see, e.g. Fig. 1).
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Truitt discloses that “[p]eripheral administration of a rho-associated protein kinase (ROCK) inhibitor is capable of improving learning and working memory in an aged rat. Myristoylated alanine-rich C-kinase substrate (MARCKS) is one of the downstream targets of the RhoA/ROCK pathway and is known to participate in several key neuronal cell functions including neurite outgrowth and growth cone adhesion. SH-SY5Y cells stimulated with increasing doses of insulin-like growth factor (IGF-1) demonstrated a both significant and rapid decrease in phosphorylated MARCKS, and a significant increase in the number of neurite bearing cells. Additionally, memory formation occurs when neurons grow and make new connections. Therefore, inhibitors of MARCKS are needed as enhancers of memory. In addition, an association between the MARCKS protein and Alzheimer's disease (AD) was suggested. Phosphorylated MARCKS was detected in the 3-Amyloid (sic) plaques of human hippocampal and parahippocampal brain tissue sections. Therefore, MARCKS' presence in the neuropathology of AD suggests a likely connection of MARCKS to AD.” ([0004]).
The reference TAN teaches that PKC is another biomarker that can indicate the pathology of Alzheimer’s disease (TAN page 11141).
Ascertaining the differences between the prior art and the claims at issue:
Alkon does not explicitly disclose MARCKS as an indicator protein.
Hasegawa does not teach each step of the instant rejected claims.
Truitt does not teach each step of the instant rejected claims.
Tan does not teach each step of the instant rejected claims.
Resolving the level of ordinary skill in the pertinent art:
The artisan is knowledgeable in the pathophysiology of Alzheimer’s disease (AD), and the molecular players thereof, such as PKC and MARCKS.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
Accordingly, it would have been prima facie obvious to a person of skill in the art before the effective filing date of the claimed invention to practice a diagnostic method of Alzheimer's disease based on comparing phosphorylation levels of a substrate protein in a test subject and a control subject, arriving at a positive diagnosis for Alzheimer's disease for the test subject based on a finding of higher phosphorylation in the test subject, based on the teachings of Alkon, and to use other substrate proteins as diagnostic markers, such as MARCKS (based on the teachings of Truitt and Hasegawa) and PKC (based on the teaching of TAN). Motivation to do so is found in view of the teachings of Hasegawa that amyloid b protein activates phosphorylation of MARCKS by both PKC and MAPK (an overlapping kinase with Alkon) in microglia and may be associated with microglia activation in Alzheimer's disease. Further motivation is in view of the teachings of Truitt that multiple signaling pathways converge on phosphorylating MARCKS, such as PKC isoforms (thus provides a motivation to suppress PKC-claims 8-9) and ROCK, that inhibitors of MARCKS are needed as enhancers of memory (thus, provides a motivation to suppress MARCKS-claims 8-9), that an association has been suggested between the MARCKS protein and Alzheimer's disease, that phosphorylated MARCKS was detected in the 3-Amyloid (sic) plaques of human hippocampal and parahippocampal brain tissue sections, and its overall conclusion that MARCKS' presence in the neuropathology of Alzheimer’s disease suggests a likely connection of MARCKS to Alzheimer’s disease. In addition, motivation lies in the teachings of TAN that PKC is a biomarker of Alzheimer’s disease (see page 11141). This teaches instant claim 1.
Moreover, given the above, the combination of references, above, render prima facie obvious instant claims 3 and 8-9. The artisan cannot detect a biomarker of Alzheimer’s disease (such as MARCKS (Truitt and Hasegawa) or PKC (Tan)) without a test compound that binds to/suppresses the biomarker. The artisan would be expected and motivated to try to suppress the biomarker MARCKS and PKC since their presence is indicative of Alzheimer’s disease (see, above). The artisan would be motivated to suppress the concentration / activity of MARCKS and PKC in the hope of thereby controlling/ameliorating/treating Alzheimer’s disease (claims 8-9). Hence, instant claims 3 and claims 8-9 are obvious as a logical extension of carrying out the detection of MARCKS and PKC biomarkers, per, above.
Conclusion
No claims are presently allowable as written.
The safe harbor provision applies prohibiting parent U.S. 11,623,946 B2 from being used in a non-statutory double patent rejection against this instant divisional application. The instant application was the non-elected and canceled group II claim 2 in a Restriction Requirement in the parent application. See MPEP 804.01.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN S KENYON whose telephone number is (571)270-1567. The examiner can normally be reached Monday-Friday 10a-6p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew D Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625