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 .
Election/Restrictions
Claims 1-41, 44, and 46-50 are cancelled.
Claims 42-43 and 45 are pending and under examination on the merits.
Information Disclosure Statement
The IDS submission dated 06/19/2025 has been considered.
Withdrawn Objections and Rejections
The objection to the specification is withdrawn as addressed by the 06/19/2025 amendments. The objections to claims 42-43 and 45 are withdrawn as addressed by the 06/19/2025 amendments. The rejections of the claims under 35 USC §101 are withdrawn and replaced with the rejections as they appear, below, in this Office Action. The rejections of the claims under 35 USC §112(a) and §103 are withdrawn as addressed by the 06/19/2025 amendments.
Maintained Claim Rejections
35 U.S.C. 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 42-43 and 45 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. The claims are directed to a judicial exception (natural correlation), specifically, the presence/increase in gene expression and a risk of developing Alzheimer Disease. Furthermore the claims do not integrate said judicial exception in to practical application, and the claim does not recite additional elements that amount to significantly more than said judicial exception.
Where a claim describes a judicial exception, such a claim “requires closer scrutiny for eligibility because of the risk that it will ‘tie-up’ the excepted subject matter and pre-empt others from using [the judicial exception]" (federal register, p.74622, C1). While all inventions to some degree involve natural laws, products, and other judicial exceptions, the new guidance regarding patent eligibility makes clear that a practical application of these exceptions is necessary, offering “significantly more” than the exception itself. Limitations that were found not to be enough to qualify as “significantly more” include:
Mere instructions to implement an abstract idea on a computer;
Adding generic instructions that the judicial exception should be used ("apply it");
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality;
Adding insignificant extrasolution activity to the exception ("mere data gathering"); and
Generally linking the use of the exception to a particular technological environment or field of use.
The MPEP (see §2103-2106.07) provides a means of determining whether a particular claim is patent eligible under 35 U.S.C. 101. The Guidance requires an analysis of multiple steps, Steps 1, 2A, and 2B:
Step 1 - Following a determination of the broadest reasonable interpretation of a claim, is the claim drawn to a process, machine, manufacture, or composition of matter? If the answer to this inquiry is “Yes,” the analysis moves on to step 2A.
Step 2A - A two-prong analysis. For prong one, does the claim recite an abstract idea, law of nature, or natural phenomenon? If “Yes,” the analysis proceeds to prong two, which asks whether the claim recites additional elements that integrate the judicial exception into a practical application. If “No,” the analysis moves on to step 2B.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? If “No,” the claim is not eligible subject matter under 35 U.S.C. 101.
In the instant case, the claims are drawn to a process, so the answer to Step 1 is “Yes.”
With respect to prong one of Step 2A, the answer is “Yes,” because as indicated above, the claims are drawn to a natural phenomenon.
The Examiner will provide a representative analysis of exemplary, independent claim 42 from which claims 43 and 45 depend.
Regarding claim 42, the claim language reciting the judicial exception is, “…treating an Alzheimer's disease in a subject, the method comprising measuring an expression level of either at least one gene selected from the group consisting of….”
Step 1 - Following a determination of the broadest reasonable interpretation of a claim, is the claim drawn to a process, machine, manufacture, or composition of matter? If the answer to this inquiry is “Yes,” the analysis moves on to step 2A. Here, the instant claim 42 recites, “ [a] method for,”. Therefore, the instant claim 1 is directed towards a method, which is a process under 35 U.S.C. 101. So the answer to step 1 is “YES.” Thus, the analysis proceeds to Step 2A.
Step 2A - A two-prong analysis. For prong 1, does the claim recite an abstract idea, law of nature, or natural phenomenon? If “Yes,” the analysis proceeds to prong 2, which asks whether the claim recites additional elements that integrate the judicial exception into a practical application. If “No,” the analysis moves on to step 2B. Here, the instant claim 42 recites a method comprising steps, including, measuring the presence/expression level of one or more biomarkers and then treating Alzheimer Disease based upon the presence/absence/expression level of said biomarkers. The correlation of naturally-occurring biomarkers with diagnosis represents a natural phenomenon, which is a judicial exception. Therefore, the answer to prong 1 of step 2A is “YES.” Thus, the analysis proceeds to prong 2 of step 2A. Here, the instant claim 42 fails to recite any claim limitations which would integrate the recited judicial exception into a practical application, for example, by applying or using said judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition with a sufficient degree of specificity. The newly added recitations of treating by administering an Alzheimer’s disease drug are recited at such a high level of generality that they do not sufficiently integrate the judicial exception into a practical application . The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s), which is not the case in the claims. Therefore the answer to prong two of the Step 2A analysis is “No” and the analysis progresses to step 2B.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? If “No,” the claim is not eligible subject matter under 35 U.S.C. 101. Here, the instant claim 42 pertains to a method of treating an Alzheimer’s disease in a subject, as discussed above. Claim 42 fails to recite additional limitations that would add significantly more than the judicial exception to the metes and bounds of the claim given that measuring steps are mere data gathering/mental steps and one of ordinary skill in the art would know that it is necessary to detect/measure expression in order to use expression as a means for diagnosis (see Mayo v. Prometheus, 566 U.S.66, 132 SA. Ct. 1289). Therefore, the answer to prong 2B is “No” and the instant claim 6 is therefore directed toward patent ineligible subject matter under 35 U.S.C. 101 and is thereby rejected under 35 U.S.C. 101.
Beginning with step 1, claim 43 is a process claim which incorporates the method (and judicial exception recited therein) of claim 42, as discussed above. Claim 43 only adds the step of measuring the level of a gene or protein encoded thereby. Per step 2A, this additional recited step fails to integrate the judicial exception into a practical application by, for example, applying or using said judicial exception to provide a particular treatment or prophylaxis for a disease or medical condition because the limitations added by dependent claims 43 and 45 only add, over claim 42, where the steps amounting to mere data gathering/mental steps (further measuring steps) which, as discussed above, are insufficient to integrate a judicial exception into a practical application for patentability. As discussed above, the recitation of “treating the subject with an anti-Alzheimer’s diseases drug” is not considered to be a specific treatment or prophylaxis steps and is therefore not a practical application. See MPEP 2106.04(d)(2). Per step 2B, claim 43 fails to recite significantly more than the judicial exception. Therefore, claim 43 is deemed directed patent ineligible under 35 USC §101.
Beginning with step 1, claim 45 is a process claim which incorporates the method (and judicial exception recited therein) of claim 42, as discussed above. Claim 45 only adds the step of measuring the level of a gene or protein encoded thereby. Per step 2A, this additional recited step fails to integrate the judicial exception into a practical application by, for example, applying or using said judicial exception to provide a particular treatment or prophylaxis for a disease or medical. The recited step of “treating the subject with an anti-Alzheimer’s diseases drug” is not considered to be a specific treatment or prophylaxis steps and is therefore not a practical application with respect to integration. See MPEP 2106.04(d)(2). Per step 2B, claim 45 fails to recite significantly more than the judicial exception. Therefore, claim 45 is deemed directed to patent ineligible under 35 USC §101.
Conclusion
No claim is allowed.
Applicant is advised that the method of claim 42 and its dependent claims 43 and 45 appear to be free from the prior art. As discussed in greater detail in the office action dated 03/19/2025, Neumann et al (as cited in the office action dated 03/19/2025) teach that, in a previous study, they introduced osteopontin (OPN) as a novel aqueous humor (AH) factor that increases with age in DBA/2J mice, a widely used animal model. OPN is encoded by the gene secreted phosphoprotein (spp1). OPN protein levels are significantly increased (interpreted to mean that the OPN expression level is higher than that in a normal control group) in neurodegenerative diseases such as Alzheimer’s. Neumann et al does not appear to explicitly teach treatment of the subject diagnosed as having AD. However, Crous-Bou et al (as cited in the office action dated 03/19/2025) teach that early intervention is being investigated for treating AD and relieving the public disease burden caused by AD (see for example the abstract and the Secondary Prevention section). Chowdhury et al (as cited in the office action dated 03/19/2025) teach that both testicans-2 and aldolase A are expressed in aqueous humor (see for example table 2). Chowdhury et al do not teach that testicans-2 or the gene encoding it (SPOCK2, also called SPARC) is associated with AD. However, Strunz et al (as cited in the office action dated 03/19/2025) teach that SPARC is highly expressed in AD brain and collocates to Aβ protein deposits, thus contributing actively to cerebral inflammation and subsequent tissue repair( see for example the abstract).
However, measurement of an expressions level of at least one of YWHAB, CNTN4 or BCHE or a protein encoded thereby, in a sample of aqueous humor, wherein a decreased expression, relative to a control, is deemed indicative of Alzheimer’s disease is not clearly made obvious by the prior art.
Perez-Gracia et al (Acta Neuropathol (2009) 118:497–504) teach YWAHB is oxidized in Alzheimer’s disease (which can impair protein-protein interaction, folding, and activity (see for example the abstract at page 497). London et al (The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol. 2013 Jan;9(1):44-53. doi: 10.1038/nrneurol.2012.227. Epub 2012 Nov 20) teach that the retina is known as an extension of the CNS. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Therefore, the eye as a valuable model to study the CNS (see for example pages 1/25-2/25).
These sources fail to render obvious the limitation of measurement of an expression level of at least one of YWHAB, CNTN4 or BCHE or a protein encoded thereby, in a sample of aqueous humor, wherein a decreased expression, relative to a control, is deemed indicative of Alzheimer’s disease when accompanied by an increase level of at least one level of SPP1, ACHE, EEF2, PRDX1, CES1, or a protein encoded thereby in the same aqueous humor sample.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The
examiner can normally be reached on M-F 9:00 am - 6:00 pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published applications
may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
applications is available through Private PAIR only. For more information about the PAIR
system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would
like assistance from a USPTO Customer Service Representative or access to the automated
information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678