DETAILED ACTION
In application filed on 06/21/2023, Claims 1-2, 4-9 and 15-17 are pending. The claim set submitted on 06/24/2026 is considered because this is the most recent claim set with some preliminary amendments. Claims 1-2, 4-5 and 9 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/21/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 06/24/2026 is acknowledged. The traversal is on the ground(s) that:
Applicant respectfully submits that the groupings as set forth in the restriction requirement are sufficiently related to be properly examined together and without undue burden on the Examiner.
Applicant traverses on the grounds that the search and examination of unelected Groups II-IV would not impose an undue burden on the Examiner. Specifically, the search and examination of Group I will encompass a search and examination for methods of detecting increased superoxide production in subjects having or suspected of having sepsis or septic shock, including measuring superoxide production in whole blood samples by chemiluminescence detection using luminol….
Accordingly, for the reasons discussed above, a search and examination of the elected Group I method will necessarily encompass subject matter in common with Groups II-IV.
In view of the above, Applicant respectfully submits that it would not be an undue burden on the Examiner to search for the inventions in all of Groups I-IV. As such, Applicant respectfully requests that the restriction requirement be reconsidered and that Groups I-IV be examined together.
Reconsideration and withdrawal of the restriction requirement are respectfully requested in view of the remarks herewith.
This is not found persuasive because the inventions as claimed are independent or distinct as set forth in the restriction requirement of 02/25/2026 and a serious search and /or examination burden exists for the reasons previously given and as further explained below. See MPEP 803.
I. Claims 1-2, 4-5 and 9, drawn to a method, classified in A61B 5/412.
II. Claims 6 and 16, drawn to a method, classified in C12N 5/0642.
III. Claim 7-8 and 17, drawn to a method, classified in A61B 5/7246.
IV. Claim 15, drawn to a system, classified in G01N 21/76.
Examiner submits that Applicant’s assertion that a single search would identify all the relevant prior art does not overcome the presentation of a different field of search and separate status in the inventions.
Examiner further asserts that overlap of some claim language or shared concept does not preclude the existence of search burden when the inventions as claimed clearly require different search strategies
The requirement is still deemed proper and is therefore made FINAL.
Claims 6-8 and 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/24/2026.
Group I, claims 1-2, 4-5 and 9 are considered on the merits below.
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 1-2, 4-9 and 15-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. All claims are directed to statutory categories, i.e., a method (Claims 1-2, 4-9 and 15-17) (Step 1: YES).
Analysis:
Claim 1: Ineligible.
Step 1:
The claim recites a series of steps or acts, including “detecting increased superoxide production in a subject having or suspected of having sepsis or septic shock relative to a subject not having sepsis or septic shock”. Thus, the claim is directed to a method, which is one of the statutory categories of invention (Step 1: YES).
Step 2A Prong 1:
Claim 1 recites “wherein the superoxide production from a sample from a subject having sepsis or septic shock is greater than the comparator result, and wherein the superoxide production from a sample from a subject suspected of but not having sepsis or septic shock is equal to or less than the comparator result” (mental step)”.
Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a mental process since claim 1 relates to using a mental process to evaluate for the comparison steps.
Also, it appears the claims that recites a natural correlation/law of nature (Step 2A, Prong 1: Patent Ineligible).
Step 2A, Prong 2:
This judicial exception is not integrated into a practical application.
Once the comparison step is done, no further action take place, , much less a particular practical application.
Also the step of “(a) measuring superoxide production in a test sample by directly contacting a test whole blood sample of 10-20 pl obtained from a subject selected from a subject having or suspected of having sepsis or septic shock and a subject not having sepsis or septic shock with phorbol myristate acetate (PMA) under conditions suitable for stimulating superoxide production in neutrophils, said contacting being at a temperature of 37-37.5°C; and (b) measuring superoxide production above basal in said test sample after a pre-determined time period of 10 minutes by chemiluminescence detection using luminol;” is recited at a high level of generality that it amounts to mere data gathering (insignificant extra-solution activity). See MPEP 2106.05(g) (Step 2A, Prong 2: NO).
Step 2B:
Furthermore, the courts have found that limitations adding insignificant extrasolution activity to the judicial exception, such as mere data gathering in conjunction with a law of nature or abstract idea, are limitations found not to be enough to qualify as ‘significantly more’ when recited in a claim with a judicial exception (see the 2014 Interim Guidance on Patent Subject Matter Eligibility of the Federal Register dated December 16, 2014; and MPEP 2106.05(I)(A)). Note that mere data gathering is not significantly more than the abstract idea. See MPEP 2106.05(g).
Here, there are no additional elements which are significantly more than the abstract idea. The steps of “(a) measuring superoxide production in a test sample by directly contacting a test whole blood sample of 10-20 pl obtained from a subject selected from a subject having or suspected of having sepsis or septic shock and a subject not having sepsis or septic shock with phorbol myristate acetate (PMA) under conditions suitable for stimulating superoxide production in neutrophils, said contacting being at a temperature of 37-37.5°C; and (b) measuring superoxide production above basal in said test sample after a pre-determined time period of 10 minutes by chemiluminescence detection using luminol” appears to be well-understood, routine, and conventional (WURC) in the field of clinical diagnostics, as evidenced by Yuasa et al. (US20110118583A1) in view of Mian et al. (US20060014235A1). (Step 2B: NO).
Therefore, Claim 1 is ineligible.
Moreover, Claims 1-2, 4-5 and 9 are rejected by virtue of their dependency on Claim 1.
In addition, the limitations of Claims 2, 4-5 and 9 do not solve the 101 issues of Claim 1.
Claim 2: Ineligible.
Step 2A, Prong One and Prong Two: Claim 2 further define the data gathering steps including the proteins measured, which appear to be generic and WURC.
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claim 2 is ineligible.
Claims 4-5 and 9 is: Ineligible.
Step 2A, Prong One and Prong Two: Claims 4-5 and 9 further recites process of determining which presents additional abstract ideas, which appear to be generic and WURC.
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claims 4-5 and 9 are ineligible.
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 1-2, 5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over by Yuasa et al. (US20110118583A1) in view of Mian et al. (US20060014235A1).
Regarding claim 1, Yuasa teaches method of detecting increased superoxide production in a subject having or suspected of having sepsis or septic shock (See Para 0030…in vivo free radicals typified by superoxide anions in systemic organ or tissue injury caused by cerebral ischemia reperfusion injury, severe infection or sepsis can be promptly and quantitatively monitored; See Para 0116…Measurement of Superoxide Concentration in an Acute Phase Ischemic Disease Model (Rats)) relative to a subject not having sepsis or septic shock (‘ a healthy man’) (See Para 0085…distinguish a patient with cerebral ischemia reperfusion injury and a healthy man based on the amount of active superoxide anion radicals; systemic organ-tissue injury caused by severe infection or sepsis can be easily diagnosed by measuring the amount of active superoxide anion radicals of a patient clinically diagnosed as systemic organ-tissue injury caused by severe infection-sepsis and setting a threshold based on this, thereby teaching “relative to a subject not having sepsis or septic shock” ), the method comprising:
(a) measuring superoxide production in a test sample by directly contacting a test whole blood sample obtained from said a subject selected from a subject having or suspected of having sepsis or septic shock (See Para 0020… a concentration of superoxide anion radicals in blood measured by said sensor electrode… comparing a concentration of superoxide anion radicals in blood measured by said sensor electrode with a predetermined threshold to distinguish a tissue injury-based value and a healthy man-based value) and a subject not having sepsis or septic shock (‘ a healthy man’) (See Para 0085…distinguish a patient with cerebral ischemia reperfusion injury and a healthy man based on the amount of active superoxide anion radicals; systemic organ-tissue injury caused by severe infection or sepsis can be easily diagnosed by measuring the amount of active superoxide anion radicals of a patient clinically diagnosed as systemic organ-tissue injury caused by severe infection-sepsis and setting a threshold based on this, thereby teaching “relative to a subject not having sepsis or septic shock” ), said contacting being at a temperature of 37-37.5°C (See Para 0171… Body temperatures (pharyngeal) were kept at 37.0° C. during the course in the sham and the control groups.); and
(c) measuring or having measured superoxide production in a sample from one or a plurality of subjects not having sepsis or septic shock to provide a comparator result (See Para 0020…‘healthy man-based value’) (See Para 0020… a concentration of superoxide anion radicals in blood measured by said sensor electrode… comparing a concentration of superoxide anion radicals in blood measured by said sensor electrode with a predetermined threshold to distinguish a tissue injury-based value and a healthy man-based value; See Para 0067…comparative means for comparing the concentration of superoxide anion radicals in blood measured by the radical sensor with a predetermined threshold to distinguish a tissue injury-based value and a healthy man-based value), wherein the superoxide production from a sample from a subject having sepsis or septic shock (‘control group’; See Para 0147…At an hour after lipopolysaccharide (LPS) administration, the O2 −. current began to increase and reached plateau at 5 hours in the LPS group) is greater than the comparator result (‘sham group’; See Para 0147… In the sham group, the O2 −. current did not change during the course) (See Para 0173…In the sham group, the O2 −. current values were significantly lower than those in the control group during the course), and wherein the superoxide production from a sample from a subject suspected of but not having sepsis or septic shock (See Para 014…In the LPS+SOD group, O2 −. generation was suppressed by the SOD administration, so that the O2 −. current was inhibited.) is equal to or less than the comparator result (See Para 0148… The Q values were significantly increased in the LPS group after 2-3 hours to 5-6 hours compared to …the LPS+SOD group).
Yuasa does not teach:
whole blood sample of 10-20 µl;
and a subject with phorbol myristate acetate (PMA) under conditions suitable for stimulating superoxide production in neutrophils,
(b) measuring superoxide production above basal in said test sample after a pre-determined time period of 10 minutes by chemiluminescence detection using luminol;.
In the analogous art of an in vitro method for quantifying exposure to psychological stress which relies on measuring the retained ability of neutrophils, preferably neutrophils in a whole blood sample, to exhibit challenge-induced superoxide anion production, Mian teaches:
whole blood sample of 10-20 µl (See Para 0050… 10 μl of whole blood was transferred into a silicon anti-reflective tube);
and a subject with phorbol myristate acetate (PMA) under conditions suitable for stimulating superoxide production in neutrophils (See Para 0004… It has now been found that exposure of both animals and humans to psychological stress can be rapidly and readily quantified by relying on measurement of the retained capacity of neutrophils in peripheral blood samples to produce superoxide anions in response to a challenge by phorbol myristate acetate (PMA), a known chemical-inducer for activating neutrophils);
(b) measuring superoxide production above basal in said test sample after a pre-determined time period of 10 minutes (See Para 0006…(b) determining the increase in superoxide production above basal in said test sample after a time period when neutrophils of the same species in a control sample; See Para 0057, 0069…10 minutes) by chemiluminescence detection using luminol (See Para 0050…To measure the background blood chemiluminescence levels, 10 μl of whole blood was transferred into a silicon anti-reflective tube (Lumivial, E G & G Berthold, Germany), to which 90 μl of 10−4M luminol (5-amino-2,3-dihydrophthalzine; Sigma A8511) diluted in phosphate buffer was added).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Yuasa to include that whole blood sample of 10-20 µl; and a subject with phorbol myristate acetate (PMA) under conditions suitable for stimulating superoxide production in neutrophils, (b) measuring superoxide production above basal in said test sample after a pre-determined time period of 10 minutes by chemiluminescence detection using luminol, as taught by Mian for the benefit of providing a method for determining whether an individual, which may be a mammal, including a human, or a bird, is experiencing changed physiological status arising from a psychological stressor (Mian, Para 0006), allowing for the benefit of quantifying stress is based on direct measures of a cellular response which forms part of the armoury of the immune system as it relies on the ability of individuals to mount a challenge-induced immune response after a potentially stressful event (Mian, Para 0005).
Regarding Claim 2, the method of claim 1 is obvious over Yuasa in view of Mian.
Yuasa teaches subject is suspected of having such an infection (See Abstract… a human body are good or not, and for diagnosing, for example, cerebral ischemia reperfusion injury, and systemic organ or tissue injury caused by severe infection or sepsis; See Para 0029… the tissue injury is systemic organ or tissue injury caused by severe infection or sepsis.)
Examiner submits that the limitation “wherein said subject is known to have an infection with an agent capable of giving rise to sepsis or” in viewed as optional and thus not required by the claim.
Regarding Claim 5, the method of claim 1 is obvious over Yuasa in view of Mian (See Claim 1 rejection)
Yuasa and Mian teaches “wherein steps (a) to (c) are applied (See Claim 1 rejection).
Further, Yuasa teaches wherein steps are applied following or during sepsis or septic shock treatment to determine the effectiveness of the treatment or monitor the treatment (See Abstract…With the device, in vivo free radicals typified by superoxide anions in systemic organ or tissue injury caused by cerebral ischemia reperfusion injury, severe infection or sepsis can be promptly and quantitatively monitored, and whether the in vivo tissue conditions are good or not can be accurately diagnosed.).
In addition, Mian teaches an in vitro method for quantifying exposure to psychological stress which relies on measuring the retained ability of neutrophils, preferably neutrophils in a whole blood sample, to exhibit challenge-induced superoxide anion production. Using such methodology, coping capacity of individuals for particular psychological stressors may be assessed (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Yuasa to include the steps (a) to (c) are applied following or during sepsis or septic shock treatment to determine the effectiveness of the treatment or monitor the treatment, as taught Mian, for the benefit of providing a method for determining whether an individual, which may be a mammal, including a human, or a bird, is experiencing changed physiological status arising from a psychological stressor (Mian, Para 0006), allowing for the benefit of quantifying stress is based on direct measures of a cellular response which forms part of the armoury of the immune system as it relies on the ability of individuals to mount a challenge-induced immune response after a potentially stressful event (Mian, Para 0005).
Regarding Claim 9, the method of claim 1 is obvious over Yuasa in view of Mian.
Yuasa does not teach “wherein in step (b) the measure of superoxide production above basal is determined per 109 neutrophils/1 to obtain a LIT- N score”.
In the analogous art of an in vitro method for quantifying exposure to psychological stress which relies on measuring the retained ability of neutrophils, preferably neutrophils in a whole blood sample, to exhibit challenge-induced superoxide anion production, Mian teaches:
“wherein in step (b) (See Claim 1 rejection) the measure of superoxide production above basal (See Para 0006…(b) determining the increase in superoxide production above basal in said test sample after a time period when neutrophils of the same species in a control sample,) is determined per 109 neutrophils/1 (See Para 0051…Although a range of leucocytes can produce a respiratory burst, neutrophils are responsible for the majority of oxygen free radical production and so leucocyte coping capacity (LCC) was also examined per quantity of 109 neutrophils/l) to obtain a LIT- N score (See Para 0051…Although a range of leucocytes can produce a respiratory burst, neutrophils are responsible for the majority of oxygen free radical production and so leucocyte coping capacity (LCC) was also examined per quantity of 109 neutrophils/l), thereby teaching “to obtain a LIT- N score”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Yuasa to include “wherein in step (b) the measure of superoxide production above basal is determined per 109 neutrophils/1 to obtain a LIT- N score”, as taught by Mian for the benefit of providing a method of examining LCC in relation to the potential effects of changes in the number of circulating neutrophils after stress (Mian, Para 0051), allowing for the benefit of quantifying stress is based on direct measures of a cellular response which forms part of the armoury of the immune system as it relies on the ability of individuals to mount a challenge-induced immune response after a potentially stressful event (Mian, Para 0005).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Yuasa et al. (US20110118583A1) in view of Mian et al. (US20060014235A1) as applied to claim1 above, and further in view of Tavaré et al. ("Recognition, diagnosis, and early management of sepsis: NICE guideline." The British Journal of General Practice 67.657 (2017): 185.) and further in view of Sanseverino, et al. ("qSOFA score for prediction of sepsis outcome in emergency department." Pakistan journal of medical sciences 36.4 (2020): 668).
Regarding Claim 4, the method of claim 1 is obvious over Yuasa in view of Mian.
The combination of Yuasa and Mian does not teach:
a method for determining the onset or occurrence of high-risk sepsis or septic shock, wherein high risk sepsis accords with the criteria of the UK NICE guidelines for such risk stratification.
In the analogous art of recognition, diagnosis, and early management of sepsis: nice, Tavara teaches a method for determining the onset or occurrence of high-risk sepsis or septic shock, wherein high risk sepsis accords with the criteria of the UK NICE guidelines for such risk stratification (See Page 185…The NICE guideline starts with a recommendation to think ‘Could this be sepsis?’ when a patient with infection contacts a healthcare professional. The guideline uses the analogy of chest pain, where the first step when a patient presents with chest pain is to exclude a cardiac cause. This is commonly done with a brief history of the nature of the pain and risk factors for cardiac disease; See Page 186… Immediate management of people with suspected sepsis is based on the results of the structured assessment. Those with suspected sepsis and high-risk criteria should be referred to acute hospital settings for emergency medical care).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Yuasa and Mian to include a method for determining the onset or occurrence of high-risk sepsis or septic shock, wherein high risk sepsis accords with the criteria of the UK NICE guidelines for such risk stratification, as taught by Tavare, for the benefit of providing a guideline that aims for a pragmatic approach where the consideration by primary care clinicians of whether someone has sepsis will hopefully reduce delay in diagnosis (Tavare, Comment Section, Page 186), allowing for the identification of biomarkers for sepsis to support clinicians’ decision making (Tavare, Comment Section, Page 186).
The combination of Yuasa, Mian, Tavare does not teach:
qSOFA score for such sepsis status according to The International Sepsis Task Force or alternative criteria for equivalent assignment of sepsis status”
In the analogous art of qSOFA score for prediction of sepsis outcome in emergency department, Shahsavarinia teaches that qSOFA score for such sepsis status according to The International Sepsis Task Force (See Abstract… The third international consensus definition for sepsis and septic shock (sepsis 3) task force recently introduced qSOFA (quick sequential organ failure assessment) as a score for detection of patients at risk of sepsis outside of intensive care units. We performed this study to evaluate the validity of qSOFA for early detection and risk stratification of septic patients in emergency department).
The limitation “or alternative criteria for equivalent assignment of sepsis status” is viewed as optional and thus not required by the claim.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Yuasa, Mian and Tavare to include “qSOFA score for such sepsis status according to The International Sepsis Task Force or alternative criteria for equivalent assignment of sepsis status”, as taught by Shahsavarinia, for the benefit of evaluating the validity of qSOFA for early detection and risk stratification of septic patients in emergency department (Shahsavarinia, Abstract), allowing for the provision that in patients with suspected sepsis, qSOFA has acceptable value for risk stratification of severity, multi organ failure and mortality. It seems that education of medical staff and frequent screening of patients for warning signs can help to increase the value of qSOFA in prediction of mortality in critically ill septic patients (Shahsavarinia, Abstract).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
Prosecution Insights