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
Acknowledgement is hereby made of receipt and entry of the communication filed on Feb. 23, 2026 and Dec. 05, 2022. Claims 1 and 3-16 are pending. Claims 1 and 3-15 are withdrawn. Claim 16 are currently examined.
Election/Restrictions
Applicant's election Group IV (claim 16) in the reply filed on Feb. 23, 2026, is acknowledged. Applicant’s interview summary in the Remarks (02/23/2026) is acknowledged.
Accordingly, claims 1 and 3-15 are withdrawn as being directed to a non-elected group.
Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
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.
Claim 16 is rejected under 35 U.S.C. §101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim 16 is directed to a method of detecting the severity level of coronavirus disease 2019 (COVID-19) in a subject, comprising measuring the level of CD16 Int low-density inflammatory neutrophil (LDN) in plasma as compared to a control.
Based on the claim. it is a recital of a natural phenomenon accompanied by additional steps that must be taken to apply the natural phenomenon (e.g., the step of taking a sample to test for a naturally occurring correlation). Adding steps to a natural biological process that only recite well-understood, routine, conventional activity previously engaged in by researchers in the field are not sufficient to render the claims patentable.
As disclosed in the instant specification, in a subject infected with virus such as SARS-COV-2 and influenza, the subjects have a distinct immunological phenotype characterized by lymphopenia and neutrophilia. Patients with an increased neutrophil to lymphocyte ratio (NLR) have reported worse clinical outcomes. Lung specimens at autopsy showed a marked infiltration of neutrophils into the lung tissue. neutrophil populations in patients with severe H1N1 influenza infection showed increased extracellular net formation (See instant specification [0003]), which indicates that the level change of neutrophil is a result and an indication of viral infection. At the same time, it is a common knowledge in the art that the CD16 is a marker of neutrophils (https://en.wikipedia.org/wiki/CD16).
The instant claims are reciting this natural phenomenon accompanied by no more than an instruction to apply the natural phenomenon using well known and routine techniques (e.g., ELISA) to carry out the natural phenomenon. While it takes a human action to trigger a manifestation of the natural phenomenon, the natural phenomenon exists in principle apart from any human action. See Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 10, 132 S.Ct. 1289, 101 USPQ2d 1961 (2012). Furthermore, the claim 16 recites “…comprising measuring the level of CD16 Int low-density inflammatory neutrophil (LDN) in plasma as compared to a control…”. These phrases are mental steps necessary for analyzing the” measuring the level” to the “control” in the application of the judicial exception. Thus, the recited “measuring” and “compared” steps of the claims do not amount significant more to the judicial exception.
Accordingly, the claim does/do not include additional elements or steps that are sufficient to amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 112
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.
Claim 16 is 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.
The claim 16 recites a phrase “detecting the severity level of coronavirus disease 2019 (COVID-19)” that render the claim indefinite. It is unclear what the criteria is used to determine if a Covid-19 disease is in a “severity level”.
The claim 16 recites a term “control” that renders the claim indefinite. It is not clear what the “control” is.
Also, the claim 16 recites a phrase “…measuring the level of CD16Int” and “…compared to a control” that render the claim indefinite. It is unclear how the “CD16Int” be measured and how the “control” is compared.
For purposes of compact prosecution and applying prior art, claim 16 was interpreted herein to encompass a control of Health group.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Rejections - 35 USC § 112 (Enablement)
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.
Claim 16 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Claim 16 contains subject matter which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Enablement is considered in view of the Wands factors (MPEP 2164.01(a)) (1) the nature of the invention, (2) the state of the prior art, 3) the breadth of the claims, (4) the amount of guidance in the specification, (5) the presence or absence of working examples, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and 8) and the quantity of experimentation necessary.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Claim 16 is directed to a method of detecting the severity level of coronavirus disease 2019 (COVID-19) in a subject, comprising measuring the level of CD16 Int low-density inflammatory neutrophil (LDN) in plasma as compared to a control.
The instant specification discloses that the present invention provides a method of detecting the severity level of coronavirus disease 2019 (COVID-19) in a patient (See [0009]) and a specific Low-Density Neutrophil Population Correlates with Hypercoagulation and Disease Severity in Hospitalized COVID-19 Patients (See Example 2, [0098]). The instant specification also discloses that the primary finding of their study is the emergence of a subpopulation of LDN in COVID-19 patients that associates with disease severity and changes over time in parallel with changing coagulation and clinical status and the CD16Int LDN are correlated with disease severity ((See [0128]). However, the instant specification does not provide support to demonstrate what exact the “severity level” is and what the “severity level” that the CD16Int LDN related to.
As for the claimed “measuring the level of CD16 Int low-density inflammatory neutrophil (LDN) in plasma”, the instant specification discloses varies factors including CD16Int for comparing the severity COVID-19 disease. For example, it discloses comparing the CD45+ lineage clusters between healthy donors, moderate, and severe COVID-19 patients. Cell lineage cluster analysis demonstrated that CD66b+CD16+ neutrophils (cluster 1, FIG. SB) were the most prominent population in COVID-19 patients (See [0065]). It also discloses that the severe patients had an elevated level of D-dimer compared to moderate patients (FIG. 4a) (See [0074]), and first measured plasma concentrations of TNF-a and IL-6 in the serial blood samples of patients compared to healthy donors (FIG. Sa), and the overall plasma level of TNF-a was low but was elevated in the severe group compared to moderate and healthy donors. IL-6 showed significant increases above moderate patients (See 0077]). Here these disclosures above indicate that there are different factors need to be measured for “detecting the severity level of coronavirus disease 2019 (COVID-19) in a subject” and the instant specification does not provide evidence to support if only measuring the “CD16 Int low-density inflammatory neutrophil (LDN) in plasma” is enough for detecting the severity level of the coronavirus disease 2019 by comparing the controls.
As for the “control”, the instant claim discloses two control groups being used in their example experiments, comorbid control and Health control (See e.g., [0103]) and states that severe COVID-19 patients showed a marked increase in the CD16 Int subset, which was significantly lower in the moderate cohort and comorbidity controls, and virtually absent in the healthy donors (FIG. 13A) (See e.g., [0107]). Thus, the specification does not provide evidence to support which control groups should be considered as a control in the comparison and which groups should be included in the comparison, where the analysis result and criteria would be different.
Accordingly, when all the aforementioned factors are considered in total, it would require undue experimentation for one skilled in the art to practice the full scope of claimed invention as defined by instant claims. Therefore, claim 16 is rejected under 35 USC § 112 (Enablement).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 16 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Morrissey et al. ( medRxiv preprint doi: https://doi.org/10.1101/2020.05.22.20106724, May 26, 2020, it is submitted by IDS filed on 04/08/2024, hereinafter “Morrissey”).
The claim 16 is directed to a method of detecting the severity level of coronavirus disease 2019 (COVID-19) in a subject, comprising measuring the level of CD16Int low-density inflammatory neutrophil (LDN) in plasma as compared to a control.
Morrissey describes an emergence of low-density inflammatory neutrophils correlates with hypercoagulable state and disease severity in COVID-19 patients and discloses that within the severe COVID-19 patient cohort, they saw the emergence of a significant population of CD16IntCD44lowCD11bIn low density neutrophils, which they refer to as low-density inflammatory band cells (LDIBs), and they further conclude that the LDIB subset contributes to COVID-19-associated coagulopathy (CAC) and could be used as an adjunct clinical marker to monitor disease status and progression. Identifying patients who are trending towards LDIB crisis and implementing early, appropriate treatment could improve all-cause mortality rates for severe COVID-19 patients (See Abstract; page 4, paragraph 2), which teaches that the level of CD16Int low-density inflammatory neutrophil (LDN) can be used to monitor/detect the severe COVID-19 patient.
Morrissey further teaches that severe COVID-19 patients showed a marked increase in the CD16Int subset, which was significantly lower in the moderate cohort, and virtually absent in the healthy donors (Figure 1b) (See bridging pages 5-6; Table 1b
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below), where the health donor (HD) is served as control. Also, in the severe patients, Morrissey teaches that there was a subset of the neutrophil population that expressed intermediate CD16, which was diminished in both the moderate and healthy donors (See page 6, paragraph 1), and tracking the CD16Int LDIB population over the course of each patients’ individual hospital stay revealed an important association between clinical outcomes and the percentage of CD16Int neutrophils (Figure S2b) (See page 6, paragraph 2).
As for the measuring the level of CD16Int low-density inflammatory neutrophil (LDN) in plasma as claimed, Morrissey teaches that the plasma concentration of the cytokine production by LDIBs, IL-6 and TNF-α, in each patient sample are detected by ELISA. In the plasma detection, the HD (health donors, n=6) are used as a control. (See Fig. 5, bridging pages 27-28; Figure 5), and the plasma is isolated as “Whole blood samples were centrifuged at 1600 rpm for 10 minutes. Plasma was aspirated and aliquoted into 1mL Eppendorf tubes and immediately stored at -80C until future use” (See page 16, paragraph 3).
Accordingly, Morrissey teaches each and every aspect of the claim 16.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am to 4:30 pm, EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached on (571) 270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RUIXUE WANG/ Examiner, Art Unit 1672