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
Summary
This is the Non-Final Office action based on the 18/032384 filed 05/20/2026.
Claims 1-12 are pending.
Claims 1-4 & 6-7 are elected and have been fully examined.
Claims 5 & 8-12 are withdrawn.
Election/Restrictions
Applicant's election with traverse of Claims 1-4 & 6-7 in the reply filed on 05/20/2026 is acknowledged. The traversal is on the ground(s) that 1: the groups were incorrectly organized, and 2: that search would not be burdensome to search all inventions. The examiner does agree that there was a mistake in the group organization and has not properly included claims 6-7 with elected group I, to make group I and the elected group include Claims 1-4 & 6-7. With respect to applicant’s argument that the search would not be burdensome if the examiner were to search all inventions at the same time, the examiner disagrees and this is not found persuasive. The examiner notes that the instant claims were restricted for lack of unity of invention and it is noted that the claimed technical features is not inventive, therefore permitting restriction, as noted in the restriction requirement dated 03/24/2026. No argument was made with respect to this, and the examiner maintains this reasoning. Further, the claims are drawn towards different statutory categories of invention and significantly different claimed for the claims which are separate groups, by the same statutory category in U.S. practice (though this is not how the restriction was done, but instead through PCT practice), and this also makes search burdensome.
The requirement is still deemed proper and is therefore made FINAL.
Claims 5 & 8-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/20/2026.
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 ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
The claimed invention of Claims 1-4 & 6-7 are directed to non-statutory subject matter.
The invention of instant claims is drawn towards a method for early diagnosis of a neurodegenerative disease.
Through 101, inquiry:
Step 1: Is the claim directed to a statutory category of invention?
Yes, the claims are drawn towards a statutory category (a method).
Step 2A, Prong 1: Do the claims involve a Judicial Exception?
For independent claim 1 and those that depend therefrom the answer is yes. Independent Claim 1 is drawn towards diagnosing, and the diagnosing is based on the amount of the 6 claimed measured metabolites. This is a natural correlation of amount of biomarker/s=disease or no disease, which is a law of nature judicial exception.
Claim 1 also includes a comparison step, to a reference. This comparison is a mental process, which is an abstract idea judicial exception.
Step 2A, Prong: Has the natural correlation or abstract idea been integrated into a particular practical application?
For Claim 1, the answer is no.
The claimed measurement, “in vitro,” is very general and is just used to perform data-gathering to accomplish the claimed judicial exception/s. Data gathering/data pulling to perform a judicial exception is considered to be insignificant extra-solution activity, and therefore does not add practical application. The claimed measuring does nothing to practically apply the judicial exceptions after they are determined. See MPEP 2106.05 (g).
After the claimed comparison step, nothing further is done. Therefore, there is no practical application.
Step 2B: Does the claim recite any elements which are significantly more than the natural correlation or abstract idea?
Again, for Claim 1, the answer is no. No specific measuring or testing is performed. As claimed, and even if a general measurement technique like mass spectrometry was used, the claimed measuring and comparing to a reference is well understood routine and conventional (WURC) in the art. See MPEP 2106.05(d)II. No specific measuring or transformation or non-routine analysis is claimed. This is especially the case at the level of generality claimed.
This is evidenced by LAWTON in US 20140303228, who teaches detecting the amount (expression level) creatine, betaine, hydroxybutyrate, acetoacetate, valine and pyruvate (paragraph 0058, 0063, 0018 Table 1), and of comparison of the levels measured of these biomarkers to references levels (paragraph 0008, 0010, 0011).
Therefore- there is nothing claimed which makes the claims significantly more than the judicial exceptions.
For the dependent claims we look to see if they add limitations that change the above analysis (e.g. does the new limitation integrate into a practical application or amount to significantly more?). Here, none of the dependent claims 2-4 or 6-7 integrate the abstract idea into a practical application at Step 2A, 2, nor do they amount to significantly more at Step 2B.
Claims 2-3 specify more metabolites that are measured however this is treated the same way as the measured metabolites for Claim 1. Their measurement is data gathering to accomplish the judicial exception and also WURC, and therefore does nothing to practically apply, nor to add significantly more to the claimed judicial exceptions.
Claim 4, specifies that the neurodegenerative disease is Parkinson’s. This is part of the natural correlation judicial exception as shown in Claim 1 and does nothing to practically apply, nor to add significantly more to the claimed judicial exceptions.
Claims 6-7 specify what the sample is (serum) and where the sample comes from (a patient with early de-novo stage disease). This sample is still used for data gathering, and it is WURC to use samples from patients at any stage of disease. Therefore, this does nothing to practically apply, nor to add significantly more.
Claim Objections
Claim 3 is objected to because of the following informalities:
With respect to Claim 3, it claims the same biomarkers as in Claim 1. In Claim 1 the biomarkers are claimed in a “at least,” sense. Therefore, it is assumed that applicant means for claim 3 to specify that only the claimed biomarkers are detected, so that it is not just repeating what was already in Claim 1. Appropriate correction is required.
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.
Claim(s) 1-4 is/are rejected under 35 U.S.C. 102 (a)(1) and 102 (a)(2) as being anticipated by LAWTON in US 20140303228.
With respect to Claim 1, LAWTON teaches of a method of detecting the levels of one or more biomarkers listed….may be determined in the methods of aiding in diagnosis whether a subject has amyotrophic lateral sclerosis (ALS), which is a neurodegenerative disease…including a combination of all biomarkers selected….maybe determined and used in such methods(paragraph 0058, Tables 1, 5,and 11). Specifically, LAWTON teaches of detecting the amount (expression level) creatine, betaine, hydroxybutyrate, acetoacetate, valine and pyruvate (paragraph 0058, 0063, 0018 Table 1), and of comparison of the levels measured of these biomarkers to references levels to determine if the patient has the disease (paragraph 0008, 0010, 0011). LAWTON teaches that in addition to diagnosing ALS, it can be early-stage ALS, and that also diseases such as Parkinson’s disease can be diagnosed with the instant method (paragraph 0055, 0083, 0041).
With respect to Claim 2, LAWTON teaches of detecting serine, lactate, glycine, threonine and leucine (paragraph 0063, Table 1).
With respect to Claim 3, LAWTON teaches of detecting creatine, betaine, hydroxybutyrate, acetoacetate, valine and pyruvate (paragraph 0058, 0063, Table 1).
With respect to Claim 4, LAWTON teaches of the neurodegenerative disease being Parkinson’s (paragraph 0041).
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 non-obviousness.
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.
Claim 6 is rejected under U.S.C. 103 as being obvious by LAWTON in US 20140303228 in view of WUOLIKAINEN in Multi-platform mass spectrometry analysis of the CSF and plasma metabolomes of rigorously matched amyotrophic lateral sclerosis, Parkinson’s disease and control subjects.
With respect to Claim 6, LAWTON teaches of a method of detecting the levels of one or more biomarkers listed….may be determined in the methods of aiding in diagnosis whether a subject has amyotrophic lateral sclerosis (ALS), which is a neurodegenerative disease…including a combination of all biomarkers selected….maybe determined and used in such methods(paragraph 0058, Tables 1, 5,and 11). Specifically, LAWTON teaches of detecting the amount (expression level) creatine, betaine, hydroxybutyrate, acetoacetate, valine and pyruvate (paragraph 0058, 0063, 0018 Table 1), and of comparison of the levels measured of these biomarkers to references levels (paragraph 0008, 0010, 0011). LAWTON teaches that in addition to diagnosing ALS, it can be early-stage ALS, and that also diseases such as Parkinson’s disease can be diagnosed with the instant method (paragraph 0055, 0083, 0041).
If it is unclear to one of ordinary skill that LAWSON teach specifically of diagnosing early stage Parkinson’s, WUOLIKAINEN is used to remedy this.
WUOLIKAINEN teaches metabolites differentiating amyotrophic lateral sclerosis (ALS) from matched Parkinson’s disease PD, and particularly in early stages and early stage samples of patients of/with the disease (abstract and Page 1288, column 2, paragraph 1). WUOLIKAINEN further teaches detection in cerebral spinal fluid CSF patients the 6 metabolites found to be significantly altered between ALS and PD according to the univariate test included α-hydroxybutyric acid and β-hydroxybutyric acid. WUOLIKAINEN (Fig 4A) teaches β-hydroxybutyrate value of zero, meaning there are higher values of β-hydroxybutyrate in ALS than in PD patients.
Therefore, it would have been obvious to one of ordinary person skilled in the art before the effective filling date of the claimed invention to diagnose or investigate early stage diseases and samples as is done in WUOLIKAINEN in the method of LAWTON due to the need in the art for better tests of ALS and PD as they often share the same early symptoms (Page 1288, column 2, paragraph 1). A person having ordinary skill in the art would have had a reasonable expectation of success because both LAWTON and WUOLIKAINEN are drawn to a method for evaluating combination the biomarkers for a neurodegenerative disease.
Claim 7 is rejected under U.S.C. 103 as being obvious by LAWTON in US 20140303228 in view of NAGELE in US 20160231335.
With respect to Claim 7, LAWTON teaches of detecting in a blood plasma sample (paragraph 0032). LAWTON does not specifically teach of using serum.
NAGELE is used to remedy this. NAGELE teaches of methods, reagents, and kits for detecting and diagnosing Early-Stage Parkinson's disease (abstract). NAGELE further teaches of detecting in serum samples (paragraph 0009).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect in serum samples as is done in NAGELE in the method of LAWTON since serum biomarkers have shown the advantage of having high diagnostic accuracy (NAGELE, paragraph 0104).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
GOOD in US 20030032070 teaches of a method for diagnosing Alzheimer's disease and Parkinson's disease in a subject by analyzing the expression of Semaphorin 3 and downstream effectors. It also provides a method for identifying a substance useful in the prevention or treatment of Alzheimer's disease and Parkinson's disease, and a method of using such substance in the treatment of Alzheimer's disease and Parkinson's disease (abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached on 571-270-7698. The fax phone number for the organization wherehis application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/ Primary Examiner, Art Unit 1758
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