DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the claims
The amendment filed 02/23/26 is acknowledged and has been entered. Claims 1, 9, 17 and 24 have been amended. Claims 16, 21, and 22 have been canceled. Claims 11-14 remain withdrawn as being directed to a non-elected invention. Accordingly, claims 1, 4-6, 9, 16-17, 19-20, and 23-24 are under examination.
Withdrawn Rejections
All rejections of claims not reiterated herein, have been withdrawn.
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.
Claims 1, 4-6, 9, 16-17, 19-20, and 23-24 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 instant claims recite “wherein the reference amounts are calculated reference amounts based on samples from the general population”. The specification on page 1 discloses that at least 1% of the general population has persistent atrial fibrillation and the frequence increases with age. The specification on pages 29-30 defines a “reference amount and mentions groups of subjects who suffered from paroxysmal atrial fibrillation or who did not suffer from paroxysmal atrial fibrillation. There is no description in the specification disclosing “wherein the reference amounts are calculated reference amounts based on samples from the general population”. The only disclosure in the specification is groups of subjects who suffered from paroxysmal atrial fibrillation or who did not suffer from paroxysmal atrial fibrillation. Furthermore, none of the originally filed claims recited the limitations in question. Recitation of claim limitations lacking literal or adequate descriptive support in the specification or originally filed claims constitutes new matter.
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.
Claims 1, 4-6, 9, 16-17, 19-20, and 23-24 are 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 1 is vague and indefinite in reciting “wherein essentially the same amounts or decreased amounts of the NT-proBNP and cardiac Troponin T in the sample from the subject as compared to the reference amounts indicates that the subject did not suffer from paroxysmal atrial fibrillation recently” because this new limitation appears to contradict steps (b) and (c) which specifically require diagnosis of a recent paroxysmal atrial fibrillation and the administration of an anticoagulation therapy to the diagnosed subject. This causes confusion as to if the applicant intends to have the claim allow for a scenario wherein the subject is not diagnosed and therefore no administration of an anticoagulation therapy is performed. Thus, it is unclear if the applicant intends the administration step as a positive step or an alternative embodiment. Please clarify.
Claim 1 the recitation “essentially the same” is vague and indefinite. The specification does not provide a definition for the phrase and it is unclear what is considered to be essentially the same. Is anything within 5% considered essentially the same. Is a difference of 0.10 considered to be essentially the same or does the applicant intend something else. Thus, the metes and bounds of the claim cannot be ascertained. See also deficiency found in claim 24.
Claim 1 is vague and indefinite in reciting “wherein the reference amounts are calculated reference amounts based on samples from the general population” and then later reciting “wherein the reference amounts are derived from (i) a subject or group of subjects known to have suffered from a recent paroxysmal atrial fibrillation, wherein the same…” because this causes confusion as to if the subject or group of (i) or (ii) is referring to the general population previously recited, if the Applicant intends an “or” situation as the general population or a subject or group of subjects known to have suffered from a recent paroxysmal atrial fibrillation, or group of subjects known not to have suffered from a recent paroxysmal atrial fibrillation. It is unclear what the Applicant is trying to encompass. See also deficiencies found in claim 24.
Claim 24 is vague and indefinite in reciting “wherein essentially the same amounts or decreased amounts of the NT-proBNP and cardiac Troponin T in the sample from the subject as compared to the reference amounts indicates that the subject did not suffer from paroxysmal atrial fibrillation recently” because this new limitation appears to contradict steps (b) and (c) which specifically require diagnosis of a recent paroxysmal atrial fibrillation and the administration of an anticoagulation therapy to the diagnosed subject. This causes confusion as to if the applicant intends to have the claim allow for a scenario wherein the subject is not diagnosed and therefore no administration of an anticoagulation therapy is performed. Thus, it is unclear if the applicant intends the administration step as a positive step or an alternative embodiment. Please clarify.
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.
Claims 1, 4-6, 9, 16-17, 19-20, and 23-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and/or to laws of nature/natural phenomena without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
The claims are directed to a naturally occurring correlation between the amount of the recited biomarkers in a subject having paroxysmal atrial fibrillation or not having paroxysmal atrial fibrillation compared to that of a reference amount.
Step 2A, Prong 2
The additional elements of detecting the recited biomarkers and comparing the amounts to a reference (as recited in claims 1& 24) does not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Also, with respect to the recitation “whereby a recent paroxysmal atrial fibrillation is diagnosed”. The “whereby” and “diagnosed” statements at best articulates the judicial exception, amounting only to a general instruction to apply or use the judicial exception. This could read on mental activity being performed solely in a practitioner’ head, e.g. A mental appreciation of the amount of the measured biomarkers as compared to that of a reference being correlated with paroxysmal atrial fibrillation. No active method steps are invoked or clearly required; the “whereby” and “diagnosed” statements do not include any activity that would constitute a practical application, i.e. steps that apply, rely on or use the natural principle in a manner such that the claims amount to significantly more that the natural principal itself.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Further, the additional elements of the claims are recited with a high level of generality and do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. (the active method steps/limitations recited in addition to the judicial exceptions themselves) and do not add significantly more to the judicial exception(s).
As shown by the art below it is well known, routine and conventional in the art to detect amounts of the recited biomarkers and compare to that of a reference and make a decision based on the comparison.
It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
Also, with respect to amended claims 1 and 24. Although the claims appear to invoke administering a treatment to the subject the claims also appear to be an optional treatment step because the claim goes on to recite “wherein essentially the same amounts or decreased amounts of the NTproBNP and cardiac Troponin T in the sample from the subject as compared to the reference amounts indicates that the subject did not suffer from paroxysmal atrial fibrillation recently”. Thus, the claim allows for a scenario wherein the amount is less than the reference and therefore the treatment step would not be performed.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well understood, conventional or routine in the field of diagnostics and biochemical assay methodologies.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 4-6, 9, 19-20 and 24 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Xiong et al (Translation, 3007, 13 pages PTO137062 Chinese article Pract Geriatr, Feb 2007, Vo. 21, No. 1). (submitted in the IDS filed 08/24/22) in view of Noonan (StopAfib.org, Study Finds Major Predictor for Development of New Atrial Fibrillation (AF), November 16, 2009, pages 1-3) and Anegawa et al (Int J Cardiol, 56 (1), pages 98-100, available online Jan. 21, 2012) or Hess et al (US 2014/0220604).
and further in view of and Holm (US20120021989A1).
With respect to the recitation, “whereby a recent paroxysmal atrial fibrillation is diagnosed” imply expresses the intended result of a process step positively recited. Diagnosis occurs passively and is the intended result of the measurement. See MPEP 2111.04. Xiong at abstract teaches a method of diagnosing a recent paroxysmal atrial fibrillation (measuring BNP after PAF) by determining the amount of BNP in a sample from the subject and comparing the determined amounts to a reference amount. Since they are separated into two groups, PAF is diagnosed (e.g. pages 2-5). Moreover, since it says measuring after PAF, the patient currently does not have a fib. Xiong at teaches that the atrial fibrillation occurred 1-7 days (48 hours) before the sample was obtained (e.g. page 5). Xiong does not teach doing anything to resolve the PAF, so it must have resolved spontaneously. Xiong at page 2 teaches a plasma sample. Xiong at pages 2-5 teaches that the subject was a human. Xiong at page 2 discloses that the comparison can be to a reference of that of a suhject(s) without a history of PAF and that increased levels are shown in subjects with a history of PAF.
With respect to claim 4, Xiong at page 2 does not teach that the patient has a stroke.
With respect to claim 6, Xiong at pages 2-5 teaches that the subject was a human.
With respect to claim 7, Xiong at page 6 teaches the BNP value of the healthy group as an average and thus is teaching the value of this group (reference) is a calculated value.
With respect to claim 8, Xiong at abstract teaches comparing to a reference amount derived from a group of subjects known to not have suffered from a recent PAF (do not have A fib) and teaches that an increase amount of the marker is indicative for diagnosis of a recent PAF.
Xiong et al differs from the instant invention in failing to teach detecting NT-proBNP and troponin T and also fails to teach the administration of an anticoagulant therapy..
Noonan teaches BNP and NT-proBNP are related biomarkers and that NT-proBNP is an inactive fragment that is produced alongside BNP, but which stays in the blood stream longer (e.g. page 1). Noonan teaches that both BNP and NT-proBNP have a correlation with atrial fibrillation and that NT-proBNP is a strong predictor for afib (e.g. pages. 1-2).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate the detection of NT-proBNP into the method of Xiong et al because Noonan teaches that BNP and NT-proBNP are related biomarkers and that NT-proBNP is an inactive fragment that is produced alongside BNP, but which stays in the blood stream longer and that NT-proBNP is a strong predictor for afib. . Further, one of ordinary skill in the art would understand that additional tests and assessments known to be correlated with atrial fibrillation would provide a more confident assessment of atrial fibrillation. It has long been held that it is obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, one of ordinary skill in the art would have a reasonable expectation of success incorporating the measurement of NT-proBNP such as taught by Noonan in the method of Xiong et al for the determination paroxysmal atrial fibrillation. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating NT-proBNP into the method of Xiong et al.
Xiong et al and Noonan differ from the instant invention in failing to teach the detecton of troponin T.
Anegawa et al throughout the reference and especially at pages 98 and 100 teaches the association of increased cardiac troponin T levels in subjects that have had atrial fibrillation as compared to that of non-AF subject (e.g. page 100).
Hess et al teaches that it is known and conventional in the art that Troponin T levels are correlated with atrial fibrillation (e.g. para 0117).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate the detection of troponin T into the modified method of Xiong et al because both Anegawa et al and Hess et al teaches that troponin T is significantly increased in atrial fibrillation subjects and one of ordinary skill in the art would understand that additional tests and assessments known to be correlated with atrial fibrillation would provide a more confident assessment of atrial fibrillation. It has long been held that it is obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, one of ordinary skill in the art would have a reasonable expectation of success incorporating the measurement of troponin T such as taught by Anegawa et al or Hess et al in the modified method of Xiong et al for the determination paroxysmal atrial fibrillation.
Xiong et al., Noonan and Anegawa et al and Hess et al differ from the instant invention in failing to teach administering an anticoagulant.
Holm, throughout the reference and especially at abstract, [0003], [0005]-[0008], [0014], and [0219]-[0222], and claims 59-61 teaches treating paf with heparin or the claimed antiarrhythmic medications and teaches treating paroxysmal atrial fibrillation in order to prevent stroke.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have administered the claimed treatment, as taught by Holm, in the modified method of Xiong because Holm teaches that this provides for the prevention of stroke in subjects having PAF and also provides for treatment of the disease. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating a treatment of an anticoagulant such as taught by Holm in the modified method and subjects of Xiong.
With respect to claim 9 as currently recited, the combination of Xiong et al, Noonan, Anegawa et al., Hess et al and Holm teach the detection of the same markers in the same subjects as currently recited and thus absent evidence to the contrary it is deemed that the modified method of Xiong et al would be indicative for the diagnosis within a period of days before the sample was obtained. Further, as stated above Xiong et al teaches that the atrial fibrillation occurred 1-7 days (48 hours) before the sample was obtained (e.g. page 5).
Claim 23 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Xiong et al in view of Noonan, Anegawa et al., Hess et al and Holm as applied to claims 1, 4-6, 9, 19-20 and 24 and further in view of Thacker et al (Neurology, 81, July 2013, pages 119-125).
See above for the teachings of Xiong et al., Noonan, Anegawa et al., Hess et al and Holm.
Xiong et al., Noonan, Anegawa et al., Hess et al and Holm differ from the instant invention in failing to teach the subject has no history of stroke.
Thacker et al teaches testing subject having atrial fibrillation wherein the subject has no history of stroke (e.g. pages 119-120).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate subjects having atrial fibrillation and no history of stroke such as taught by Thacker et al into the modified method of Xiong et al because Thacker et al shows that it is known and conventional in the art. Further, one of ordinary skill in the art would recognize that subjects having a history or stroke could alter the results of subjects and correlation with atrial fibrillation.
Allowable Subject Matter
Claim 17 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, and 35 U.S.C. 101 set forth in this Office action. The prior art of record does not teach nor fairly suggest detecting IGFBP7 in combination with the recited biomarkers and correlating the measurement with paroxysmal atrial fibrillation.
Response to Arguments
Applicant's arguments filed 02/23/26 have been fully considered but they are not persuasive.
103 Rejections:
Applicant argues that Noonan does not motivate substituting NT-proBNP into Xiong’s method.
This argument is not found persuasive because the Examiner has not substituted NT-proBNP for the BNP in Noonan but has stated that the level is incorporated into the method of Xiong. Thus, the Examiner is adding the NT-proBNP marker along with the marker(s) in the method of Xiong. Further, it is noted that the instant claims use “comprising” language and thus the claims are open to additional markers, reagents and steps.
Applicant further argues that the only prior art reference teaching any Troponin in connection with AF is Van Den Bos that teaches troponin I and not troponin T.
This argument is not found persuasive because (1) the Examiner had also applied Hess et al for teaching troponin T (see Non-Final action mailed 11/21/25 and the rejection of claim 21)(the Applicant failed to address this reference). (2), the Examiner has now applied Anegawa et al to amended claim 1 to further show that it is well known, routine and conventional in the art that troponin T is associated with atrial fibrillation.
Applicant argues that In re Kerkhoven is inapplicable because the purpose of the claimed invention is the retrospective diagnosis of recent PAF in subject currently in sinus rhythm.
This argument is not found persuasive because (1) the Examiner did not rely solely on Kerhoven but also stated that one of ordinary skill in the art would recognize that combining markers known to be associated with atrial fibrillation would provide further confirmation in the method of Xiong; and thus even if Kerkhoven was removed the rejection would be maintained; (2) the Examiner is relying upon Xiong for the primary showing of the atrial fibrillation, the occurrence within 30 days etc and the secondary references for showing biomarkers correlated with atrial fibrillation and thus all the markers being associated with the same condition such as atrial fibrillation and thus are related to the same purpose of diagnosing atrial fibrillation; (3) there is nothing in the claims concerning sinus rhythm.
Applicant argues unexpected results and points the Examiner’s attention to Example 3 and a showing that Troponin T remains elevated above the reference value, whereas NT-proBNP drops dramatically and that this differential kinetic pattern enables a tiered temporal diagnostic algorithm not taught or suggested by any cited reference.
This argument is not found persuasive because there is nothing in the claims about an algorithm. Thus, the Applicant’s arguments are not on point.
Applicant then makes reference to amended claim 9 and states that this tiered temporal diagnostic algorithm is not taught or suggested by any combination.
This argument is not found persuasive because this is not directed to a calculated algorithm or recite anything directed to a computer use of an algorithm. (NOTE: it is noted that an algorithm is an abstract idea and thus would not provide any additional element to this judicial exception and thus would fall under 101). Further, as stated supra the combination of Xiong et al, Noonan, Anegawa et al., Hess et al and Holm teach the detection of the same markers in the same subjects as currently recited and thus absent evidence to the contrary it is deemed that the modified method of Xiong et al would be indicative for the diagnosis within a period of days before the sample was obtained. Further, as stated above Xiong et al teaches that the atrial fibrillation occurred 1-7 days (48 hours) before the sample was obtained (e.g. page 5).
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678