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 .
Status of Application, Amendments and/or Claims
1. Claims 24-27, 30-31, 36-37, 41 and 43-46 are pending and under examination in the present application.
Information Disclosure Statement
2. The information disclosure statement (IDS) filed 10/10/2025 has been considered and the references therein are of record.
Maintained Claim Rejections
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.
3. Claims 24-27, 30-31, 36-37, 41 and 43-46 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The rejection is maintained for reasons of record and as discussed below.
The basis of this rejection has been set forth previously and therefore will not be fully reiterated here. See sections 6-8 of the 04/11/25 office action (OA), sections 4-6 of the 09/21/23 OA, section 6 of the 01/06/22 OA, and sections 5-7 of the 12/23/22 OA.
Response to Arguments
4. In the response filed 10/10/2025, applicant reviews the analysis under 2019 PEG as well as MPEP guidance in asserting that the present claims demonstrate integration of a judicial exception. In particular, it is argued that conventional techniques for the diagnosis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) were limited in that diagnosis was only achieved at advanced stages of dementia, when therapeutic interventions were limited. According to applicant, the present claims provide an improvement to the diagnosis of neurodegenerative disease (“dilution of the plasma with sample buffer results in an increase in detectable levels of Ab1-40 and Ab1-42”, which peptide levels are used for determining the presence or state of neurodegenerative disease), allowing for earlier detection of neurodegenerative disease (ND) and/or a state prior to ND, and thus enabling earlier therapeutic treatment.
Applicant further argues that the treatment for MCI as recited by the claims is specific (i.e., the subject is treated when measured Ab peptide values are greater than predetermined values), and consistent with such alleged integration.
Therefore, it is argued that the judicial exception is integrated into a practical application, i.e., earlier detection and treatment of MCI and ND.
5. Applicant’s arguments have been fully considered but are not persuasive. First, Applicant is reminded that claims are analyzed with respect to their broadest reasonable interpretation (BRI), and for contingent claims, “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. For example, assume a method claim requires step A if a first condition happens and step B if a second condition happens. If the claimed invention may be practiced without either the first or second condition happening, then neither step A or B is required by the broadest reasonable interpretation of the claim. If the claimed invention requires the first condition to occur, then the broadest reasonable interpretation of the claim requires step A. If the claimed invention requires both the first and second conditions to occur, then the broadest reasonable interpretation of the claim requires both steps A and B” (MPEP 2111.04(II)).
The BRI of independent claim 24 thus is a method that comprises: obtaining a blood sample from a human subject; separating the blood sample into plasma and cell fractions; diluting the plasma fraction with a protein solubilization agent and measuring the concentration of Ab1-40 and/or Ab1-42 in the diluted plasma (2ab40 or 2ab42); diluting the cell fraction with a protein solubilizing agent and measuring the concentration of Ab1-40 and/or Ab1-42 in the cell fraction (3ab40 or 3ab42); and preparing values based upon the measured peptide concentrations, or sums of two or more measured concentrations. Note that the final recited step, “treating the subject for mild cognitive impairment when the aggregate is greater than 71.1 pg/ml for 3ab40, 50.3 pg/ml for 2ab42, 132.7 pg/ml for 2ab40+3ab40, or 235.5 pg/ml for 2ab40+3ab40+2ab42+3ab42”, is contingent upon the condition that one or more of the measured values (or sums of values) is found to be greater than a predetermined value; if the predetermined level is not exceeded, then treatment does not occur and the method ends with “preparing an aggregate [value]”. In this way, the BRI of the claims does not require treating a subject for MCI. The claims preempt all forms of measuring these innate biomarkers and, therefore, preempt “‘basic tools of scientific and technological work’ that lie beyond the domain of patent protection” Myriad, 569 U.S. 576, 589, 106 USPQ2d at 1976, 1978 (noting that Myriad discovered the BRCA1 and BRCA1 genes and quoting Mayo, 566 U.S. 71, 101 USPQ2d at 1965). See MPEP 2106.04.
Regarding a treatment step as a consideration of integration of a judicial exception into a practical application, MPEP 2106.04(d)(2) makes clear that “in order to qualify as a ‘treatment’ or ‘prophylaxis’ limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. […] If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the ‘treatment or prophylaxis’ consideration.” (emphasis added) This later example applies to the instant claims which recite treatment that is contingent upon the outcome of the measuring/analyzing steps. According to the instant claim, only if the subject is determined to have MCI based upon a measured values of Abeta peptides that are greater than predetermined values. If the measured values are not greater than the predetermined levels, then there is no treatment. Therefore, the treatment step of the instant claims cannot integrate the judicial exception of the claims into a practical application because the claims do not affirmatively require an action that effects a particular treatment of a disease.
Further, even if the step of “treating” was non-conditional and a required step of the claims, in contrast to applicant’s assertions the treatment is not a particular treatment. MPEP 2106.04(d)(2)(a) notes that:
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). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application.
In the instant case, the treatment is not a specific or particular treatment, and therefore does not integrate the judicial exception into a practical application.
Finally, in response to applicant’s assertion that the invention constitutes an improvement in the technology, MPEP 2106.06(b) states that this must be a clear improvement in the technology. The dilution of plasma and cell pellets to improve the availability of proteins for detection was a technique that was routine and conventional in the prior art (see, for example, section 8 of the 04/11/2025 OA), and therefore does not constitute an improvement as asserted. Moreover, any treatment of a subject is, again, contingent upon the determination of the subject having certain Abeta peptide values greater than predetermined values. The claims, therefore, do not necessarily result in any improved technology.
For all these reasons, the claims do not amount to significantly more than the judicial exception(s) itself, and claims 24-27, 30-31, 36-37, 41 and 43-46 stand rejected under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
6. Claims 24-27, 30-31, 36-37, 41 and 43-46 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The rejection is maintained for reasons of record and as discussed below.
The basis for this rejection has been set forth previously (see section 9 of the 04/11/2025 OA) and therefore will not be fully reiterated here. In brief, the specification as filed does not provide adequate support for a method of treating a human subject having mild cognitive impairment (MCI), wherein the subject is treated for MCI following measuring the level(s) of various amyloid-beta peptides within a blood sample of the subject and determining that the level(s) are above predetermined values for those peptides or combinations of peptides.
Response to Arguments
7. In the response filed 10/10/2025, applicant argues that the analysis of whether the specification complies with the written description requirement requires comparison of the claim scope to the scope of the description to determine whether applicant had possession of the claimed invention, wherein such determination is conducted via the standpoint of one of ordinary skill in the art at the time the application was filed. Applicant contends that the specification provides “detailed discussion regarding neurodegenerative disease, specifically, Alzheimer’s disease (AD) and the prodromic stage of said disease known as mild cognitive impairment (MCI).” According to applicant, the specification discloses a description of “specific clinical, neurological, and biological characteristics of neurodegenerative disease…. including the existence and limitations of therapeutic measures for treatment of advanced disease. See e.g., [0006]. An ordinary skilled artisan, at the time of filing, would understand treatments and therapeutic measures which may be used for neurodegenerative disease, including those with senile plaques and vascular amyloid deposits (amyloid angiopathy).” Applicant thus argues that the specification provides ample guidance to the skilled artisan and satisfies the written description requirement.
8. Applicant’s arguments have been considered but are not persuasive. As stated at p. 1 lines 5-7 of the specification as filed, “[t]he invention relates to the field of immunoassays and, more specifically, to the methods for increasing the sensitivity of immunoassays for the determination of amyloid beta peptides in biological fluids.” Indeed, the title of the present application is “Methods and Reagents for Improved Detection of Amyloid Beta Peptides”, and the abstract discusses methods for the diagnosis of neurodegenerative disease, for the detection of a stage prior to a neurodegenerative disease, or for distinguishing neurodegenerative disease from a stage prior to a neurodegenerative disease. In other words, the present application as filed is wholly directed to the detection and diagnosis of neurodegenerative disease, and specifically AD.
While “limited” therapeutic measures are mentioned in the background of the invention with respect to diagnosis of neurodegenerative disease in patients suffering from advanced dementia (at, e.g., [0006]), this does not provide adequate guidance nor support for the treatment of a subject having MCI as claimed. Both at the time of filing and now, there are no therapies that are specific for the treatment of MCI in a human subject that would be recognized as such by one of skill in the art. While MCI is often referred to as a stage prior to AD (as in the instant application), the prior art recognizes that MCI may be a prodromal stage to dementia in general, or else it may be its own clinical entity altogether. For example, Maioli et al. (Arch Gerontol Geriatr. 2007;44 Suppl 1:233-241)1 studied the conversion of MCI to dementia in elderly subjects, and found that a substantial number of elderly with MCI never converted to dementia. Of those who did convert, just over half (53.3%) developed AD, AD with cerebrovascular disease accounted for 33.4% and fronto-temporal dementia accounted for 13.3% of converters. Thus, not every subject having MCI goes on to develop dementia, and even for those who do convert to dementia, not all patients develop AD.
The skilled artisan would have therefore understood that treatment type may vary based upon the particular subtype of MCI; however, no such distinction in the type of treatment for AD-type MCI is provided by the instant application. The specification does not describe treatments that are specific for MCI, nor for particular subtypes of MCI as would be recognized by one of ordinary skill in the art. Moreover, the specification does not even describe or provide disclosure for any treatments that are specific for AD or any other particular neurodegenerative disease.
Accordingly, one of skill in the art would not have recognized that applicant was in possession of a method for the treatment of MCI in a human subject as claimed. The written description rejection under 35 U.S.C. 112 is therefore maintained.
Conclusion
9. No claims are allowed.
10. THIS ACTION IS MADE FINAL. 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.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly A. Ballard whose telephone number is (571)272-2150. The examiner can normally be reached Mon-Fri 8AM - 5PM EST.
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
1 This reference was added only to address specific arguments of applicant’s response filed 10/10/25, and does not change the basis of the rejection of record.