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 Final Office action based on the 16/979118 response filed 09/05/2025.
Claims 1 & 3-8 are pending and have been fully considered.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, orcomposition of matter, or any new and useful improvement thereof, may obtain a patenttherefor, subject to the conditions and requirements of this title.
The claimed invention is not directed to patent eligible subject matter. Basedupon consideration of all of the relevant factors with respect to the claim as a whole, claim(s) 1 & 3-8 is/are determined to be directed to a law of nature and abstract idea.
The rationale for this determination is explained below:
Step 1: Are the claims directed to a statutory category of invention?
Yes, independent Claims 1 & 8 and those that depend therefrom are directed to a method.
Step 2A, Prong One: Identify the law of nature/natural phenomenon/abstract ideas.
Independent claims 1 & 8 recite, “measuring,” triglycerides in LDL-TG in blood to determine the risk of developing cardiovascular disease. The level of LDL-TG is then correlated with if the patient has or is likely to have the cardiovascular disease. This is a law of nature/ natural correlation and therefor the claims recite a judicial exception. Further “determining risk,” as recited in the preamble is an abstract idea.
Step 2A Prong Two: Has the abstract idea been integrated into a particular practical application?
No.
For the measuring, two options are claimed in Claim 1 and Claim 8 for how the measuring can occur which both involve: “treatment with a surfactant that acts on lipoproteins other than LDL,” “treatment with lipoprotein lipase, glycerol kinase, and glycerol-3-phosphate oxidase,” and in some instances with also “cholesterol esterase,” and “measuring the amount of hydrogen peroxide produced,” which is indicative of the LDL-TG in the blood.
It is also claimed that if LDL-TG is determined to be above a threshold of 17 mg/dL to 40 mg/DL, then the patient has an increased risk of cardiovascular disease coronary heart disease, or cerebral stroke.
While the claimed measuring/ treatment with a specific combination of enzymes is fairly specific--- the judicial exception (natural correlation of LDL-TG) is not fully integrated into a practical application in the claims since it is not specified how one goes from detecting hydrogen peroxide to determining if LDL-TG level is above the threshold of 17 mg/dL to 40 mg/dL.
Right now, the LDL-TG measurement steps--- wherein “amount of hydrogen peroxide,” is the result, read as extra-solution activity since the connection between detecting hydrogen peroxide and determining if LDL-TG level is above the threshold of 17 mg/dL to 40 mg/dL is not clearly claimed.
Further—after the claimed measuring, no action is taken. Therefore, there is no particular practical application.
Especially at the level of generality claimed there is no practical application.
No particular or specific measurement or detection device is used and it is not apparent as claimed if the instantly claimed measuring is performed by a sensor or specific detector or if specific types of detection of any kind occur.
Further, determining if the patient is at risk for disease or not is not fully integrated with the claimed general measuring in the claim. It is only claimed what “indicates,” the amount of LDL-TG which is the amount of hydrogen peroxide. But, after that there is no indication on how one goes from a measured level of hydrogen peroxide to determining if a threshold level of LDL-TG, not hydrogen peroxide which is what is actually measured as claimed, is above of below 17mg/dL to 40 mg/dL. The claims indicate that “the amount of hydrogen peroxide is indicative of the amount of LDL-TG,” but without a more specific tie of how hydrogen peroxide level relates to the LDL-TG level the claims read as the judicial exception (LDL-TG correlation with cardiovascular disease, coronary heart disease, or cerebral stroke), is determined and that something completely different (hydrogen peroxide), is measured. Therefore- the measurement of the completely different thing, hydrogen peroxide reads as extra solution activity.
Further, as claimed in the 101 rejection…treating a sample with a general surfactant and with lipoprotein lipase, glycerol kinase, and glycerol-3 phosphate oxidase as claimed seems to treat or physically change or promote hydrogen peroxide and not the LDL-TG.
Therefore, since the claims are not fully written to integrate the claimed measuring into a practical application-the claimed measuring currently reads as data gathering to be used in the natural correlation, and is insignificant extra-solution activity, and not a particular practical application. See MPEP 2106.05(g).
Step 2B: Does the claim recite any elements which are significantly more than the abstract idea?
Here, we look to the elements other than the law of nature/natural correlation to see if there is significantly more.
For the claimed measuring, two options are claimed in Claim 1 and Claim 8 for how the measuring can occur which both involve: “treatment with a surfactant that acts on lipoproteins other than LDL,” “treatment with lipoprotein lipase, glycerol kinase, and glycerol-3-phosphate oxidase, in the presence of a surfactant that acts on LDL,” and “measuring the amount of hydrogen peroxide produced,” which is indicative of the LDL-TG in the blood.
While the claimed measuring/ treatment with a specific combination of enzymes is fairly specific--- the judicial exception (natural correlation of LDL-TG to the presence or likelihood of cardiovascular disease/risk of that) ---the measuring at claimed is not specifically connected to the claimed judicial exception/natural correlation as claimed. Further as shown by the prior art rejection--- using the claimed combination of enzymes to measure hydrogen peroxide is a technique that is something that is well-understood, routine and conventional (WURC). Therefore, as claimed, the additional elements do not amount to significantly more. See MPEP 2106.05(d)- “The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.”
It is also claimed that if LDL-TG is determined to be above a threshold of 17 mg/dL to 40 mg/DL, then the patient has an increased risk of cardiovascular disease coronary heart disease, or cerebral stroke, however this is part of the judicial exception itself.
The dependent claims undergo the same analysis.
Claims 3-4 specify which option of (a) or (b) for the measurement with enzymes in claim 1 is used. This does not change the matters in claim 1 in that the judicial exception is not fully integrated into a practical application, and that the claimed measurement technique for measuring hydrogen peroxide is not significantly more than the claimed judicial exception since it is WURC in the art.
Claims 5-6 specify what surfactant is used for measurement that acts on lipoproteins other than LDL in claim 1 is. This does not change the matters in claim 1 in that the judicial exception is not fully integrated into a practical application, and that the claimed measurement technique for measuring hydrogen peroxide is not significantly more than the claimed judicial exception since it is WURC in the art.
Claim 7 narrows down the range for the threshold value. This is part of the judicial exception/natural correlation itself and therefore does not change matters.
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.
Claims 1 & 3-8 are rejected under 35 U.S.C. 103 as being obvious over OHTA in US 20150132834 in view of BROWN in US 20190227085.
With respect to Claims 1, 3 & 8, OHTA et al. teach of a method of quantifying LDL-TG (abstract), and of its association with disease (specifically heart or liver disease) (paragraph 0002-0003). OHTA et al. also teach of measuring serum samples for the levels of LDL-TG (paragraph 0063-0067), and specifically of measuring samples with the claimed levels of LDL-TG (paragraphs 0067 & 0074 & Table II).
OHTA et al. further teach that inventors quantification of triglycerides in LDL can be achieved by degrading triglycerides in non-LDL lipoproteins as much as possible by increasing the selectivity and specificity, and then adding a surfactant reactive with the remaining LDL in the subsequent step to decompose the LDL, followed by degrading triglycerides in the LDL by the action of lipoprotein lipase, glycerol kinase and glycerol-3-phosphare oxidase, and then quantifying the produced hydrogen peroxide (paragraph 0010, 0024, 0026, 0038, 0040, and abstract).
OHTA et al. further teach that LDL-TG can hardly be detected in healthy patients (though hardly also means that is still can be detected- it is just in low amounts) and that it increases in patients with liver disease and further progresses as the disease progresses and that this is also true with coronary artery diseases (paragraphs 0003-0004). Therefore- though OHTA does not specifically call out using samples from healthy patients, this teaching makes it obvious that one could measure LDL-TG in a patient (healthy or not) and use the measurement to tell you that if the level is elevated above a certain level the patient has a disease or is likely to progress/develop in the future to be one who has the disease.
OHTA do not call out the comparison threshold of 17-40mg/dL for LDL-TG indicating cardiovascular disease risk. BROWN is used to remedy this.
BROWN teaches of a method of diagnosing cardiovascular disease (abstract) and specifically of measuring LDL-TG, and even more specifically of a range of around 17mg/dl to around 40 mg/dl of LDL-TG /being the inflection point for increased risk of cardiovascular disease (See Figure 5 C. & 5F & paragraph 0052, 0137).
It would have been obvious to one of ordinary skill in the art to detect cardiovascular disease by the threshold taught in BROWN in the method of OHTA due to the need in the art for better forms of detection and treatment of cardiovascular disease and the advantage of using a control level for making diagnoses, 0006 (BROWN, paragraph 0004).
With respect to Claim 4, OHTA et al. teach of removing/eliminating hydrogen peroxide (abstract, paragraphs 0010-0011, 0024-0027), and of using a second reagent for measuring a second amount of hydrogen peroxide (paragraph 0010).
With respect to Claim 5-6, OHTA et al. teach of using polyalkylenes as surfactants with HLB values of 13-15(paragraphs 0030-0031), and specifically of using one not less than HLB 11(paragraph 0042). KATAYAMA et al. also teach of using polyalkylenes with an HLB value of 13 or higher (paragraph 0010, 0035-0036).
With respect to Claim 7, OHTA teaches of the claimed invention as shown above for Claim 1. OHTA do not call out the comparison threshold of 17-40mg/dL for LDL-TG indicating cardiovascular disease risk. BROWN is used to remedy this.
BROWN teaches of a method of diagnosing cardiovascular disease (abstract) and specifically of measuring LDL-TG, and even more specifically of a range of around 17mg/dl to around 40 mg/dl of LDL-TG /being the inflection point for increased risk of cardiovascular disease (See Figure 5 C. & 5F & paragraph 0052, 0137).
It would have been obvious to one of ordinary skill in the art to detect cardiovascular disease by the threshold taught in BROWN in the method of OHTA due to the need in the art for better forms of detection and treatment of cardiovascular disease and the advantage of using a control level for making diagnoses, 0006 (BROWN, paragraph 0004).
Response to Arguments
Applicant's arguments filed in response dated 09/05/2025 have been fully considered but they are not persuasive.
In response dated 09/05/2025 no amendments were made.
Applicant argues with respect to the 101 rejection which was added in post applicant filing an appeal brief dated 11/26/2024 and post consultation with two appeal conferees in an appeal conference with respect to this brief.
During the appeal conference, the conferees decided that the judicial exception recited in the instant claims (presence or likelihood of having cardiovascular disease, cerebral stroke or coronary heart disease, is not fully integrated into a practical application, as instantly claimed. The examiner maintains this decision in the instant Final rejection--- especially since no amendments were made.
To further explain how the claimed judicial exception is not fully integrated, further clarification is provided within the 101 rejection as shown above and also here.
Specifically, determining if the patient is at risk for disease or not is not fully integrated with the claimed general measuring. It is only claimed what “indicates,” the amount of LDL-TG which is the amount of hydrogen peroxide. But, after that there is no indication on how one goes from a measured level of hydrogen peroxide to determining if a threshold level of LDL-TG, not hydrogen peroxide which is what is actually measured as claimed, is above of below 17mg/dL to 40 mg/dL. The claims indicate that “the amount of hydrogen peroxide is indicative of the amount of LDL-TG,” but without a more specific tie of how hydrogen peroxide level relates to the LDL-TG level the claims read as the judicial exception (LDL-TG correlation with cardiovascular disease, coronary heart disease, or cerebral stroke), is determined and that something completely different (hydrogen peroxide), is measured. Therefore- the measurement of the completely different thing, hydrogen peroxide reads as extra solution activity.
Further, as claimed in the 101 rejection…treating a sample with a general surfactant and with lipoprotein lipase, glycerol kinase, and glycerol-3 phosphate oxidase as claimed seems to treat or physically change or promote hydrogen peroxide and not the LDL-TG. Therefore , due to the disconnect between that and the claimed judicial exception, the 101 rejection is maintained.
With respect to the 101 rejection, applicant argues that the 101 rejection is based on incorrect legal standard and cites 3 exhibits. Applicant argues that the claimed processing/measuring as claimed using the general surfactant and lipoprotein kinase, glycerol kinase, and glycerol-3-phosphate oxidase is not WURC in the art and that the examiner saying it is so based on the prior art teaching this is incorrect legal standard.
The examiner disagrees. The examiner maintains that as shown in the 101 rejection--- the examiners conclusion that what is claimed is WURC in the art is not only based on the prior art, but also due to how applicant is claiming the information and in that it is not fully integrated with the claimed judicial exception. Therefore—the rejection is maintained.
Applicant further argues with respect to the 101 rejection that it is not factually correct--- due to an Exhibit 4, which is a Declaration by Ernst J. Schafer. The examiner has reviewed the Declaration submitted 09/05/2025, but is not convinced--- again due to how the instant substance is claimed. In the Declaration submitted 09/05/2025, Dr. Schafer submits support for their opinion that the steps recited in (a) and (b) of Claims 1 & 8 were not WURC.
With respect to this—the examiner again points out that the examiners conclusion that what is claimed is WURC in the art is not only based on the prior art, but also due to how applicant is claiming the information and in that it is not fully integrated with the claimed judicial exception.
At this time it is unclear if the judicial exception were to be fully integrated with the claimed judicial exception if a different position with respect to the Declaration would be formed or not.
With respect to the prior art, applicant mentions the prior rejection that was made which was OHTA in view of KATAYAMA, prior to the appeal. The examiner notes that this rejection was not made in the Non-Final rejection after appeal and that OHTA in view of BROWN was used.
With respect to the prior art rejection of OHTA in view of BROWN, applicant argues that the prior art does not teach of determining risk, “in the future,” as claimed. The examiner disagrees.
The examiner points out that OHTA, the primary reference teaches that LDL is a “risk factor,” for arteriosclerosis and coronary artery disease (paragraph 0002). This makes determining a “risk” factor obvious.
Applicant calls out “in the future,” as another claim limitation that they think the examiner has not considered and that OHTA does not teach a “predictive value.” The examiner notes that “predictive value,” is not claimed. Though, again- the examiner disagrees with applicant overall. The examiner points out that OHTA, the primary reference teaches that LDL is a “risk factor,” for arteriosclerosis and coronary artery disease (paragraph 0002). A risk factor is something which means a patient is likely to experience a condition in the future--- therefore, the teaching of a risk factor, make the “in the future,” and use as a “predictive value,” obvious.
Applicant also argues that the examiner does not consider that the instant method is required to be performed on samples from “healthy individuals.” The examiner again disagrees. OHTA teaches of using healthy individuals (paragraph 0003-0004) and though OHTA does not specifically call out “detecting in,” healthy patients, it makes it obvious to do so. Further determining risk factor as shown above--- also indicates looking for disease in patients not currently affected by the condition, which can be considered “healthy,” patients.
Applicant only argues about the BROWN reference to say they do not think BROWN cures any purported deficiencies of OHTA. The examiner disagrees that there are deficiencies in OHTA other that the way shown in the 103 rejection above (with respect to the claimed threshold).
Therefore, all claims remain rejected.
Conclusion
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.
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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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758