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 1-14 are pending and under examination in the present application.
Information Disclosure Statement
2. The information disclosure statement filed 06/28/2022 has been considered and the references therein are of record.
Priority
3. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of ES 201631468 has been filed both in the current application as well as in parent Application No. 15/804,689, filed on 11/06/2017.
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.
4. Claims 1-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon and abstract idea judicial exceptions without significantly more. The claim(s) recite(s) an in vitro method for diagnosing Alzheimer's disease (AD), which diagnosis is based upon the content of a biomarker in CSF, or else the ratio of the biomarker content in CSF to content in blood/plasma. The natural correlation between the level or ratio of the biomarker (mercaptoalbumin (HMA)) and the presence of AD is not only a natural phenomenon, but it may also be considered a law of nature because it describes a consequence of natural process in the human body, e.g., the naturally-occurring relationship between reduced HAM levels/ratios and the manifestation of AD. Additionally, the “determining” and “comparing” steps in claims 1 and 7 can be construed as abstract ideas, because they cover performance of the steps in the mind, and read upon observing, evaluating, and/or forming a judgement or opinion. Thus, the claims are directed to at least one judicial exception.
This judicial exception is not integrated into a practical application because claim 1 only recites determining the content of HMA in a sample and comparing the determined content to HMA content in (healthy) control subjects. Claims 2-4 simply provide further information on the comparison, and claims 5-6 define the subject population from whom the sample being tested is obtained. Similarly, claim 7 merely recites “determining” and “comparing” steps (i.e., determining content of HMA in a sample, determining a difference or ratio, and comparing the difference/ratio with a difference/ratio in healthy subjects). Dependent claims 8-14 further qualify the ratio, the comparison, or else the subject population. However, these determination and comparison steps must be completed in order to perform the diagnostic method, and therefore may broadly be considered as data gathering steps. As such, the claims do not integrate the natural correlation phenomenon into a practical application because the claims do not impose any meaningful limits on practicing the method.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the “determining” and “comparing” steps are all a part of the judicial exception encompassed by the claimed diagnostic method. The instant specification at p. 2 indicates that human albumin is the most important protein in the blood plasma, “constituting up to 60% of total plasma proteins (citation provided). Similarly, albumin is also the most abundant protein in the CSF, constituting around 67% of total proteins (citation provided).” The art at the time of filing generally recognized the redox properties of human serum albumin (HSA) and the antioxidant activities of HSA against oxidative damage. For instance, in the review by Anraku et al. (Biochim. Biophys. Acta, 2013, 1830:5465-5472; listed on IDS), the authors teach that the ratio of the oxidized form of HSA (HNA) to the reduced form (HMA) (i.e., HNA/HMA), which is a function of the redox states of Cys34, could serve as a useful marker for evaluating systemic redox states and thus for the evaluation of disease progression and therapeutic efficacy. This view is echoed in another review by Roche et al. (FEBS Lett. 2008, 582:1783-1787; listed on IDS), which teaches that HSA can sustain oxidative damage as the result of disease or pathology and that the oxidized form of the protein thus can serve as a biomarker of oxidative stress, as well as in a publication by Nagumo et al. (PLoS ONE, 2014, 9(1):e85216; listed on IDS), which reports that the degree of oxidized cysteine 34 (Cys34) in HSA is correlated with oxidative stress related to pathological conditions.
The measurement of HMA in cerebrospinal (CSF) and blood samples was also routinely and conventionally performed in the art at the time of filing. See, for example, Imai et al. (Japanese J. Physiol. 2002, 52:135-140; listed on IDS), Era et al. (Int. J. Pept. Protein Res. 1988, 31(5):435-42; listed on IDS), Matsuyama et al. (J. Physiol Sci. 2009, 59(3):207-215; listed on IDS), as well as the Nagumo et al. (2014) reference cited above. Thus, methods consistent with the claimed analysis of HMA content in biological samples, such as CSF and serum, were well-understood, routine and conventional in the art at the time of filing.
Accordingly, when all of the elements are considered, both individually and in combination, the claims as a whole do not amount to significantly more than the judicial exception(s). Therefore, the claims are not patent eligible.
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.
5. Claim 4 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 4 recites the limitation "the cut-off value" in line 1. There is insufficient antecedent basis for this limitation in the claim.
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.
6. Claim(s) 1-11 and 13-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Matsuyama et al. (J. Physiol Sci. 2009, 59(3):207-215; listed on IDS).
Matsuyama et al. teach a method that comprises determining the content of mercaptoalbumin (HMA) in both cerebrospinal fluid (CSF) and serum samples from adult humans (see Fig. 2 at p. 210), which addresses the method of present claims 1 and 7, as well as limitations of present claims 5-6 and 13-14. As discussed above, the “comparing” step in claims 1 and 7, and the “determining a difference or ratio” in claim 7 all amount to mental steps that could be performed within the human mind, and therefore do not aid in distinguishing the claimed subject matter from the disclosure of the prior art. Determining a ratio also reads upon performing a mathematical operation, which is also a mental activity or abstract idea. The distinction between a claim and the prior art cannot reside solely in a feature of the claimed invention that, standing alone, is not patentable subject matter. Further, the BRI of the conditional limitations of present claims 2-3 and 9-10 (i.e., diagnosing if the determined amount/difference is determined to be something) allows for performing the method even when these conditions are not met. Finally, the limitations relating to a cut-off value in claims 4 and 11 speak to arbitrary values related to mental steps (i.e., determining) and therefore do not overtly limit the performance of the claimed methods. As such, the method performed by Maysuyama anticipates the methods of the present claims.
7. Claim(s) 1-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lackner et al. (US 2014/0234988 A1; listed on IDS).
Lackner et al. disclose the use of redox-modified forms of human serum albumin as biomarkers for diagnosing a medical condition associated with oxidative stress (see abstract), such as Alzheimer's disease (AD) (see [0021] and [0059]). The method comprises determining in a test sample derived from a subject the redox state of albumin at the cysteine residue 34 (Cys34), quantifying the level of non-mercaptalbumin-2 (HNA2), and comparing the result obtained with a control level, wherein an elevated level of HNA2 compared to the control is indicative of the presence and/or prognosis of the medical condition associated with oxidative stress (see [0044]-[0047]). Lackner teaches that typically, in healthy humans, HMA accounts for 70-80%, HNA1 for 20-30%, and HNA2 for 2-5% of total albumin (see [0064]). Therefore, an increase in HNA2 would necessarily mean a reciprocal decrease in one or both of HMA and/or HNA1.
Lackner, for example, demonstrates the measurement of HMA, HNA1 and HNA2 in plasma samples using HPLC, for example, in Example 1 (see in particular [0092]). In addition to plasma samples, Lackner discloses that samples can include CSF (see [0051]). Thus, Lackner provides for a method that comprises determining the content of HMA in CSF and plasma samples, which addresses limitations of claims 1, 7 and 12.
With respect to claims 5 and 13, Lackner teaches that the subject is human (see [0050]). Given that AD is a disease associated with age, the subjects tested for AD would therefore all necessarily be adults, as in present claims 6 and 14.
Finally, as noted above, the conditional limitations of claims 3-4 and 9-10, and the cut-off values of claims 4 and 11 do not serve to limit the claimed invention nor distinguish it from the prior art teachings of Lackner. Accordingly, the disclosure of Lackner anticipates the present invention of claims 1-14.
Conclusion
8. No claims are allowed.
Advisory Information
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
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