DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Applicants filed response on 2/5/2026 has been received.
Claim 25 has been canceled. Claim 30 is added.
Claims 1-24, 26-30 are pending and under examination.
Applicants filed terminal disclaimers for US12270816, US10551394, US12025623, US9857386 have been approved. US12399188, US10197582, US9347960, US11474116 has a later filing date and later expiration date. Therefore there is no need for a terminal disclaimer for extending the patent life.
Objection to claim 1 and 23 for clarity on “Cer” and “PC’ is withdrawn because of amendment.
The rejection on claim(s) 1-24 and 26-29 under pre-AIA 35 U.S.C. 102 (e ) as being anticipated by Meikle (II) (WO 2011063470) is withdrawn because Meikle (II)(priority depending on Meikle (I) provision application 61264767) assaying actual experiencing coronary artery disease (CAD) patients, whereas the current methods focus on the risk (in the future) of complications of cardiovascular disease patients based on ongoing prospective study by follow-up observing complications, such as death, myocardial infarction, angina pectoris, transient ischemia attack after blood-withdrawal (see current specification section 0153, 0163-0165). As it is known that not all CVD patients will develop the above complications during their lifetime (see Cheng (Eur. Heart J. 2013 November page 1-9; IDS); also Allonen Clin. Cardiol. 2012 35:22-27). Accordingly, the rejection on Claim 25 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Meikle as applied to claims 1-24 and 26-29 above, and further in view of Stahlman (J. Chromatography B 2009 877:2664) as evidenced by Eejsing (Anal. Chem. 2006 78:6202) is withdrawn.
The rejection on claims 1-24 and 26 are rejected under 35 USC 101.
As to claim 1 and 26, the law of nature refers to the (1) measuring natural molecules from a subject, i.e. the recited lipid metabolites in samples, and (2) correlating an increase or decrease of the metabolites for cardiovascular disease. Therefore, the natural relationship is the biomarker(s) correlating with a “condition” under judicial exception. (See Mayo Collaborative Servs. v. Prometheus Laboratories, Inc., 132 S.Ct. 1289 (2012)(on claims 1 and 26).
With regard to claims 2, 3 and 26, determining effective treatment in a subject resembles to the Prometheus scenario (Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) where a treatment was administered to the patient followed by measuring related drug-metabolite. This administering step does not provide a significant weight to the claim amounting more than law of nature. It is because this step is not one that applies, relies on, or uses the judicial exception (Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals (2018)). The step of treating the subject is merely part of data-gathering process. One clinician cannot determine how a treatment works unless administering the treatment to the subjects followed by measuring the biomarkers (MPEP 2106.05(a)). In another word, the initial treatment testing here is not the step one clinician does in response to the law of nature, i.e. identified different lipid metabolites or ratios thereof in patient and treating the identified patient accordingly (See Vanda holding). Overall, the law of nature is at the end of the instant claim, i.e. correlating the levels, i.e. decreased of biomarkers to the phenomena (improved) of organic acidemia. Note, the term “treatment” in claims 20-22 does not specify any particular therapeutic or agent, therefore simply “rest” can be considered under broadest reasonable interpretation and thus patentable weight is given. No additional element adds to the claim amounting significantly more than mere judicial exception.
Next, whether the claims recite additional elements that integrate the judicial exception into a practical application. The answer is No. The issue is whether the amendment feature “wherein the determining step(s) comprise(s) spiking the sample with a synthetic non-endogenous Cer and/or PC internal standard”. Using internal standard for quality assurance is well-known and commonly practiced in the field. For instance, Meikle (III)(US 20080233655) teaches using Cer(ceramide) and PC (phosphatidylcholine) as internal standard for analysis lipid metabolites (section 0084). In addition, Shi (US 20070111316) teaches analyzing lipid metabolites using PC as internal standard (section 0193). Moreover, Watkins (US 20040143461) also teaches using PC as an internal standard for analysis for analyzing lipid metabolites (section 0086). Note, the above Ceramide and PC are non-endogenous synthetic, and administering (spiking) to the samples for quality of the lipid metabolites quantitation. Using these internal standards can be considered part of the assay to ensure quality of the assay. It is not a practical application. Assuming arguendo the internal standard is a practical application, nevertheless it still falls into “well-known, common and routine practice in the field” (see below)
Under Step 2B, whether a claim amounts to significantly more. The answer is No. The instant steps, such as obtaining samples, measuring biomarkers, comparing and correlating are well-understood, routine, conventional activity in the field and add insignificant extra-solution activity to the judicial exception. For instance, the specification illustrates using conventional mass spectrometry. Also using internal standard in an assay for quality assurance is known (see above). These steps are recited at a high level of generality, and are necessary data gathering steps that feed into the determining step. One cannot do the determining step without getting the data. This weighs against it being significantly more.
Applicants’ arguments are summarized below:
Applicants’ arguments mainly centers on USPTO training example 29 claim 5 (Life Sciences Examples, 5/6/2016). The claim 5 in the example 29 shows below:
Claim 5 is directed to a method of diagnosing and treating julitis in a patient, said method comprising: a) obtaining a plasma sample from a human patient;
b) detecting whether JUL-1 is present in the plasma sample; and
c) diagnosing the patient with julitis when the presence of JUL-1 in the plasma sample is detected; and
d) administering an effective amount of topical vitamin D to the diagnosed patient.
According to the example, prior to applicant's invention, and at the time the application was filed, Vitamin D was known to doctors and was routinely and conventionally used as an oral supplement to maintain bone health prior to applicant's invention, and at the time the application was filed. However, mere knowledge of vitamin D or its use in other ways to treat other medical conditions does not make the administration of topical vitamin D to treat julitis a conventional step that those in this field would routinely practice. The evaluation turns on whether the use of topical vitamin D was "widely prevalent" in the field at the time the invention was made and the application was filed. Because it was not, the recitation of administering topical vitamin D is an unconventional step that is more than a mere instruction to "apply" the correlation and critical thinking step (the exception) using well-understood, routine or conventional techniques in the field. Whether taken alone or as a combination with the other additional elements, the recitation of administering topical vitamin D yields a claim that amounts to significantly more than the exception itself. Accordingly, claim 5 of example 29 is patent eligible.
Analogous to claim 5 of Example 29 in the Life Sciences Examples, instant independent claims 1-3 and 26 also include steps in addition to the alleged judicial exception, e.g., spiking the samples with a synthetic non-endogenous Cer and/or PC internal standard. Applicants submit that, at the time of filing, the use of synthetic non-endogenous lipid internal standards, such as Cer and/or PC as described in the instant claims, was not widely prevalent in the field of predicting CVD complication risk and assessing or choosing prophylactic treatments thereof. Because it was not, the recitation of "wherein the determining step(s) comprise(s) spiking the sample with a synthetic non-endogenous Cer and/or PC internal standard" is an unconventional step that is more than a mere instruction to "apply" the alleged judicial exception using well-understood, routine or conventional techniques in the field. Moreover, the use of non-endogenous synthetic Cer and/or PC internal standards in combination with the steps of determining the concentration of lipid(s) as described in the present claims results in surprisingly accurate lipid quantitation and ensures that false positives are minimized. Thus, subjects are less likely to be erroneously identified as those who are e.g., at risk of one or more CVD complications as was commonplace in the art.
Applicant’s arguments have been considered but are not persuasive.
As has been discussed above and the citations of Meikle (III), Shi and Watkins, it has shown that using PC and/or ceramide as an internal standard for measuring lipid metabolites can be considered a part of the assay for assurance of performance quality. It is known and practiced in the field. Moreover, the criteria for novelty, i.e. correlation of the lipid metabolites along with the internal standard with the diagnosis of CVD complication is different from judicial exception. Using the lipid panel for diagnosis and evaluating effectiveness of a treatment may be novel. But the correlation with the common and routine practice cannot weigh the claims significantly more than law of nature.
Clams 27-29 are not under 35 USC 101, judicial exception. The reason is that although measuring natural occurring lipid metabolites as recited, however there is no correlation of the presence or increase/decrease to the CVD complication because the identification of CVD risk took place prior to the measurement of the lipid metabolites. Thus judicial exception does not apply. Moreover, claims 27-29 are allowed because terminal disclaimer has been approved (2/5/2026).
Conclusion
Claims 1-24 and 26 are not allowed.
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.
/CHANGHWA J CHEU/ Primary Examiner, Art Unit 1678