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 the claims
The amendment filed 05/22/26 is acknowledged and has been entered. Claims 1-3, 5, 15, 17-18 and 22-23 have been amended. Claims 25-26, 32, 34-35 and 37-38 remain withdrawn as being directed to non-elected inventions. Accordingly, claims 1-5, 13, 15-20, 22 and 23 are under examination.
Withdrawn Rejections
Applicant’s argument and statement that binding domains refer to different spots on an assay surface is found persuasive and thus the 112(b) rejection directed to “binding domains” has been withdrawn.
All remaining rejections not reiterated herein, have been withdrawn.
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 22-23 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 levels of the recited biomarkers in a human subject exposed to radiation.
Step 2A, Prong 2
The additional elements of combining a biological sample with the recited reagents, forming complexes and measuring the complexes 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 “determining if: the concentration of biomarker IL-15 is higher compared to a control; it. the concentration of biomarker CD5 is lower compared to a control; if the concentration of biomarker Fit-3L is higher compared to a control; if the concentration of salivary amylase is higher or the same compared to a control, wherein if any of (1), Gi), (it) or (iv) is true, reporting that the human has been exposed to radiation, wherein the control of (1), Gi), Gu}, and (iv) is from a human who has not been exposed to radiation.”. The “determining” statement 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 recited biomarkers being correlated with radiation exposure in the subject. No active method steps are invoked or clearly required; the “determining” statement does 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 art below it is well known routine and conventional in the art to combine a biological sample with the recited reagents, forming complexes and measuring the complexes.
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.
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 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 nonobviousness.
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, 5, 13, 15-16 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Cooper et al (WO 2015/006515) in view of Blakely et al (WO 2013/049455) (submitted in the IDS filed 05/03/22).
Cooper et al discloses a method for the assessment of ionizing radiation by measuring the amounts of biomarkers in a subject such as a human (e.g. abstract, pgs 2-3, 7). Cooper et al discloses that the sample can be a blood sample (e.g. page 7). Cooper et al discloses measuring a panel of biomarkers and discloses that the panel of biomarkers can comprises FLt3L, salivary alpha amylase (AMY1A) and IL-15 (e.g. pgs 2, 4). Cooper et al discloses the panel can comprise 3 or more biomarkers (e.g. page 2). Cooper et al discloses that the measurement can be performed by immunoassay and that the immunoassay can be a multiplex platform which allows for simultaneously measuring the biomarkers (e.g. page 8). Cooper et al discloses the immunoassay comprising capture antibodies specific for each biomarker (e.g. page 8) and using detection antibodies to bind the complexes and detection the complexes (e.g. page 8). Cooper et al discloses the assessment of ionizing radiation comprises measuring the biomarkers and comparing the values to that of a control and making an assessment of the exposure to radiation (e.g. abstract, pages 2, 33) by reporting the amounts of the biomarkers or the assessment of exposure (e.g. page 3, para 19).
Cooper et al differs from the instant invention in failing to teach the detection of CD5 (as recited in claims 1 & 17) and the detection of an additional biomarker such as CD20 (as recited in claims 15 & 20).
Blakely et al teaches that CD5 and CD20 associated with ionizing radiation and teaches that both CD5 and CD20 have decreased levels in subjects exposed to the radiation (e.g. pgs 18-19 and 47). Blakely et al teaches that the CD5 and CD20 can be measured by immunoassay and the use of antibodies for the biomarkers (e.g. pgs 29-30).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to further include the detection and measurement of CD5 and CD20 and antibodies such as taught by Blakely et al into the method of Cooper et al because Blakely et al teaches that both CD5 and CD20 are decreased in subjects exposed to ionized radiation and one of ordinary skill in the art would understand that additional tests and assessments known to be correlated with radiation would provide a more confident assessment of the radiation. Further, 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). Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating the detection and measurement of CD5 and CD20 and antibodies such as taught by Blakely et al into the method of Cooper et al. Further, it would have been obvious to report the results of the assessment as one of ordinary skill in the art would recognize
Claims 2, 17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Cooper et al in view of Blakely et al as applied to claims 1, 5, 13, 15-16 and 22-23 above, and further in view of Jacobs et al (US 2002/0095073).
See above for the teachings of Cooper et al and Blakely et al.
Cooper et al and Blakely et al differ from the instant invention in failing to teach each of the binding reagents immobilized on associated binding domains.
Jacobs et al discloses microarrays comprising multiple probes such as antibodies that are all bound to substrate to allow for the simultaneous detection of analytes (e.g. para’s 0007-0016, 0022, 0044-0057, 0066-0068). Jacobs et al teaches that different assays such as sandwich immunoassays and competition immunoassays can used for the detection (e.g. para 0084). Jacobs et al teaches that each analyte is detected in a different section such as a well wherein each well is for a different analyte (i.e. a different binding domain for each analyte (e.g. para’s 0014-0019, 0084, and Figures). Jacobs et al teaches that this provides for a method for detecting almost any biological analyte and provides easy and simple read-out results and can be easily automated and used with robots and technologies currently used in clinical testing laboratories (e.g. para’s 0030-0034).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate microarrays and detection such as taught by Jacobs et al into the modified method of Cooper et al because Jacobs et al teaches that this provides for a method for detecting almost any biological analyte and provides easy and simple read-out results and can be easily automated and used with robots and technologies currently used in clinical testing laboratories. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating microarrays and detection such as taught by Jacobs et al into the modified method of Cooper et al.
Claims 3-4 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Cooper et al in view of Blakely et al and Jacobs et al as applied to claims 1-2, 5, 13, 15-17, 20 and 22-23 above, and further in view of O’Connor et al (US 2010/0330684).
See above for the teachings of Cooper et al., Blakely et al and Jacobs et al.
Cooper et al., Blakely et al and Jacobs et al differ from the instant invention in failing to teach adding a competing reagent for binding to salivary amylase.
O’Connor et al teaches that it is known and conventional in the art salivary amylase can be detected by competitive immunoassay wherein a reagent that binds to an immobilized antibody is added and wherein the reagent competes with salivary amylase for binding to the antibody (e.g. para 0045).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate a competitive reagent for salivary amylase such as taught by O’Connor et al into the modified method of Cooper et al because Jacobs et al in the modified method of Cooper specifically teaches that the detection of the analytes can be performed by competitive immunoassay and thus one would use the appropriate competitive reagents in the modified method of Cooper et al for the detection of salivary amylase by competitive immunoassay. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating a competitive reagent for salivary amylase such as taught by O’Connor et al into the modified method of Cooper et al.
Response to Arguments
Applicant's arguments filed 05/22/26 have been fully considered but they are not persuasive.
101 Rejections:
Applicant argues that claims 22 and 23 are not "directed to the correlation between the levels of the recited biomarkers in a human subject exposed to radiation," as alleged by the Office, nor do they seek to protect any correlation by itself. Rather, the claims have integrated therein an active step of conducting a specific multiplexed assay using a specific combination of biomarkers. Conducting the multiplexed assay to measure the specific combination of biomarkers is critical to determining radiation exposure. Applicant further states that the claims are not directed to a naturally occurring correlation, and when viewed as a whole, the claims clearly provide a technical solution to the problem of needing to determine radiation exposure, by performing a specific multiplexed assay as featured in claim 1 to measure the levels of a specific set of biomarkers, i.e., the combination of IL-15, CD5, Flt-3L, salivary amylase, and CD20. The critical active step of measuring the recited combinations of biomarkers is integrated into the method, and thus the claims cannot be considered to be "directed to" a judicial exception under Step 2A.
This argument and statements are not found persuasive because the instantly recited claims are “directed to” a naturally occurring correlation between the levels of the recited biomarkers in a human subject exposed to radiation. ”Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception (Federal Register/Vol 79, 74622, No. 241/Tuesday, December 16, 2014/Rules and Regulation) (2014 Interim Eligibility Guidance Quick Reference Sheet). Therefore, the rejection is maintained. Further, with respect to the use of a “specific combination” as argued by the Applicant. The instant claims use comprising language (open language) and recites “at least five biomarkers” therefore, the claims allow for hundreds or even thousands of biomarkers as long as IL-15, CD5, Flt-3L, salivary amylase and CD20 are included and thus is not considered a limited specific combination. Further, as stated in the previous office action the detection of these complexes are considered additional elements which do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Applicant disagrees that the recited "determining" step merely articulates a judicial exception or constitutes a mental process. The "determining" expressly relies on conducting the multiplexed immunoassay of claim 1, as recited in step (a) of claim 22. The multiplexed assay cannot be "a mental activity being performed solely in a practitioner's head" as alleged by the Office. Thus, even if the claims "apply a natural correlation," which Applicant does not concede, the claimed method requires conducting a multiplexed immunoassay. Subsequently, the "determining" step is tied to performing an assay, which is a practical step, and thus cannot be performed in a practitioner's head. The claims are therefore eligible under Step 2A.
This argument is not found persuasive because as stated supra and in the previous office action the steps of the multiplex assay are considered additional elements which do not rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception and thus are considered using well known, routine and conventional steps for gathering information. The “determining” part of the claim can read as a mental step of appreciating the values of the detected markers be correlated with radiation exposure. As stated above and in the previous office action No active method steps are invoked or clearly required; the “determining” statement does 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.
Applicant again argues that the claims feature measuring a specific combination of biomarkers which provide improvements
This argument is not found persuasive because The instant claims use comprising language (open language) and recites “at least five biomarkers” therefore, the claims allow for hundreds or even thousands of biomarkers as long as IL-15, CD5, Flt-3L, salivary amylase and CD20 are included and thus is not considered a limited specific combination. Further, as stated in the previous office action the detection of these complexes are considered additional elements which do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. With respect to an improvement as argued by the Applicant. This argument is not found persuasive because the claim itself does not reflect the disclosed improvement in the technology. The current claim does not provide a step of medical intervention which applies the judicial exception in a manner which adds more to the claim. The current claims are not acting or using a practical application but are coming up with an information of the biomarkers. The claims do not have a step of using the information in a manner that imposes a meaningful limit. Thus, the current steps are not acting on or using the judicial exception in a practical application and that the steps are merely coming up with an information of the levels of the recited biomarkers but not applying this information with medical intervention.
103 Rejections:
Applicant argues that the claims feature a specific panel of biomarkers and that Cooper describes panels of biomarkers all of which include ACT and that ACT is a critical component in the Cooper method and that the removal of this critical component would render the prior art invention being modified unsatisfactory for its intended purpose.
This argument is not found persuasive because it appears that the Applicant is arguing that the instant claims are limited to only the 5 recited biomarkers. This argument is not found persuasive because the instant claims use comprising language (open language) and recites “at least five biomarkers” therefore, the claims allow for hundreds or even thousands of biomarkers as long as IL-15, CD5, Flt-3L, salivary amylase and CD20 are included and thus is not considered a limited specific combination and the instant claims therefore allow for additional biomarkers such as ACT included with the recited biomarkers.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GARY COUNTS/ Primary Examiner, Art Unit 1678
Prosecution Insights