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 .
Election/Restrictions
Applicant's election without traverse of Group I, claims 11, 12, 14-15, 18, 21 and 22 in the reply filed on December 18, 2025 is acknowledged.
Claims 24-31 are withdrawn as being drawn to non-elected invention.
Claims 11, 12, 14-15, 18, 21 and 22 are under examination in this Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 6, 2022 has been considered by the examiner.
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 11, 12, 14-15, 18, 21 and 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. 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. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because.
Claims consist of well understood, routine, conventional activity already engaged in by the scientific community and is taught in prior art discussed in the 103(a) rejection below.
The claims are drawn to A method for determining the presence of SARS-CoV-2 (COVID-19) infection in a subject or for determining the viral stage of infection of a SARS-CoV-2 (COVID- 19) illness in a subject suffering therefrom, comprising: (a) obtaining a biological sample from the subject; (b) measuring on a platform expression levels of a plurality of pre-defined set of gene products in said biological sample, wherein the plurality of pre-defined gene products comprises 10, 20, 30, 40, 50 or more of the weighted genes listed in TABLE 7; or 5, 8, 10, 12 or 14 or more of the weighted genes listed in TABLE 8; (c) normalizing the gene product expression levels to generate normalized expression values; (d) entering the normalized gene product expression values into a SARS-CoV-2 (COVID-19) infection classifier, said classifier(s) comprising pre-defined weighting values for each of the gene products of the plurality of pre-determined gene products for the platform, optionally wherein said classifier is retrieved from one or more databases; and(e) calculating a presence or an etiology probability for the SARS-CoV-2 (COVID-19) infection based upon said normalized expression values and said classifier, and optionally determining a threshold for the determination of SARS-CoV-2 (COVID-19) infection, to thereby determine the presence or viral stage of SARS-CoV-2 (COVID-19) infection in the subject.
The claims inform a relevant audience about certain laws of nature and recite mental method steps such as measuring and calculating. Thus, the present claims are drawn to the statutory category of a process. See Step 1 of the Revised Guidelines.
Doehn et al. (Infection, 2021, p. 757-762) teach SIGLEC1 associated with SARS-Cov-2.
Lu et al. (Journal of Medical Virology, 2021, p. 582-584) teaches elevated MUC1 and MUC5AC mucin protein levels in airway mucus of critical ill COVID-19 patients (see the entire document).
The claims inform a relevant audience about certain laws of nature, the presence of elevated SIGLEC1 and other genes in patients infected with SARS-CoV-19. Therefore, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. Laws of nature constitute non-statutory subject matter. Mayo Collaborative Services v. Prometheus Laboratories, Inc., 101 USPQ2d 1961 (U.S. 2012).
The first step in determining whether a claim recites patent eligible subject matter is to consider whether the claims recite an abstract idea, law of nature or natural phenomenon. See Prong One of Step 2A of the Revised Guidelines.
As noted above, the claims are drawn to A method for determining the presence of SARS-CoV-2 (COVID-19) infection in a subject or for determining the viral stage of infection of a SARS-CoV-2 (COVID- 19) illness in a subject suffering therefrom, comprising: (a) obtaining a biological sample from the subject; (b) measuring on a platform expression levels of a plurality of pre-defined set of gene products in said biological sample, wherein the plurality of pre-defined gene products comprises 10, 20, 30, 40, 50 or more of the weighted genes listed in TABLE 7; or 5, 8, 10, 12 or 14 or more of the weighted genes listed in TABLE 8; (c) normalizing the gene product expression levels to generate normalized expression values; (d) entering the normalized gene product expression values into a SARS-CoV-2 (COVID-19) infection classifier, said classifier(s) comprising pre-defined weighting values for each of the gene products of the plurality of pre-determined gene products for the platform, optionally wherein said classifier is retrieved from one or more databases; and(e) calculating a presence or an etiology probability for the SARS-CoV-2 (COVID-19) infection based upon said normalized expression values and said classifier, and optionally determining a threshold for the determination of SARS-CoV-2 (COVID-19) infection, to thereby determine the presence or viral stage of SARS-CoV-2 (COVID-19) infection in the subject.
The judicial exceptions are the diagnosing, monitoring and comparing steps, which are mental steps.
The judicial exceptions are based on the relationship between increased levels of LY6E, IFIT1, OASL, IFI27, CCL2, LAMP3, RSAD2, GBP1, ISF15, IFIT5, DDX58, ATF3, SEPT4 and more and the presence of SARS-CoV-2 in a patient. The mental step of comparing biomarker levels is similar to comparing information regarding a sample or test subject to a control or target data (see Univ. of Utah Research Found, v. Ambry Genetics Corp., 113 USPQ2d 1241 (Fed. Cir. 2014), or diagnosing an abnormal condition by performing clinical tests and thinking about the results (see In re Grams, 12 USPQ2d 1824 (Fed. Cir. 1989)). The answer to Prong One of Step 2A is yes.
The second step in determining patent-eligibility of claimed subject matter is to consider whether the claims recite additional elements that integrate the judicial exception into a practical application. The claims require “providing a biological sample” and “determining the expression level” of LY6E, IFIT1, OASL, IFI27, CCL2, LAMP3, RSAD2, GBP1, ISF15, IFIT5, DDX58, ATF3, SEPT4.
Sample collection, however, is merely the necessary data gathering required in order to perform the mental analysis of diagnosing, monitoring and comparing. Likewise, the methods employed for determining (measuring) the LY6E, IFIT1, OASL, IFI27, CCL2, LAMP3, RSAD2, GBP1, ISF15, IFIT5, DDX58, ATF3, SEPT4 are part of the necessary data gathering.
The final step in determining whether claims recite patent eligible subject matter is to consider whether the claims recite additional elements that amount to significantly more than the judicial exception. Dependent claim 21, recites “wherein the method further comprises administering to the subject an appropriate treatment regimen based on the etiology determined by the methods” and claim 22 recites: “The method according to claim 21 in which the appropriate treatment regimen comprises an antiviral therapy or an anti-SARS-CoV-2 (COVID- 19) therapy.”
The additional elements recited in claims 21 and 22 do not recite significantly more than the judicial exception because they only suggest a treatment in general without reciting any specific treatment, such as a specific medication being administered in a patient. Thus, present claims 21 and 22 fail to recite additional elements that amount to significantly more than the judicial exception.
The claims merely recite additional steps that append well-understood, routine and conventional activities previously known to the industry and specified at a high level of generality to the judicial exception (see MPEP 2106.05(d)).
Thus, claims 11, 12, 14-15, 18, 21 and 22 do not recite patent-eligible subject matter.
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.
Claims 11, 12, 14-15, 18, 21 and 22 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 pre-AIA the applicant regards as the invention.
Claims are drawn to A method for determining the presence of SARS-CoV-2 (COVID-19) infection in a subject or for determining the viral stage of infection of a SARS-CoV-2 (COVID- 19) illness in a subject suffering therefrom, comprising: (a) obtaining a biological sample from the subject; (b) measuring on a platform expression levels of a plurality of pre-defined set of gene products in said biological sample, wherein the plurality of pre-defined gene products comprises 10, 20, 30, 40, 50 or more of the weighted genes listed in TABLE 7; or 5, 8, 10, 12 or 14 or more of the weighted genes listed in TABLE 8; (c) normalizing the gene product expression levels to generate normalized expression values; (d) entering the normalized gene product expression values into a SARS-CoV-2 (COVID-19) infection classifier, said classifier(s) comprising pre-defined weighting values for each of the gene products of the plurality of pre-determined gene products for the platform, optionally wherein said classifier is retrieved from one or more databases; and(e) calculating a presence or an etiology probability for the SARS-CoV-2 (COVID-19) infection based upon said normalized expression values and said classifier, and optionally determining a threshold for the determination of SARS-CoV-2 (COVID-19) infection, to thereby determine the presence or viral stage of SARS-CoV-2 (COVID-19) infection in the subject.
The recitation of Tables 7 and 8 within the claims render the claims indefinite. See 2173.05(s): Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). Correction is required.
Additionally, the recitation of “normalizing the gene product expression levels to generate normalized expression values” renders the claims indefinite as it is unclear what the metes and bound or the recited normalization are.
Clarification and/or correction is required.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 11, 12, 14-15, and 18 are rejected under 35 U.S.C. 103 as being unpatentable and obvious over Mann et al. (WO 2018/154075 in IDS on 12/6/2022) in view of van Moorsel et al. (Frontiers in Medicine, May 16, 2020, p. 1-8).
Mann et al. teaches a method for diagnosing whether a subject is contagious with an RNA respiratory virus or predicting whether a subject will become contagious with an RNA respiratory virus, such as influenza virus, the method comprising measuring the expression levels of one or more genes selected from USP18, MAP2K6, ATF3, BCL2L14, CCL2, CCL8, CXCL10, DDX58, GBP1P1, HERC6, IFIH1, IFIT2, LAMP3, OAS2, PANK2, PML, PNPT1, TDRD7, and TOR1B in a biological sample taken from the subject and assigning the subject to a class corresponding to the subject's degree or predicted degree of contagiousness by analyzing the expression levels of the one or more genes and using (see claims 1-68, pages 7-11, paragraphs [0034-0057], page 13, paragraph [0067], page 14, paragraph [0074], page 16, paragraph [0081], page 17, paragraph [0084], page 24, paragraph [00141], Figure 16, Table 1).
Mann et al. do not teach SARS-CoV-2.
Van Moorsel et al. teach a method for diagnosing a coronavirus infection comprising detecting the presence of MUC5B mRNA in COVID-19 patients (see Materials and Methods and Results).
It would have been prima facie obvious to the person of ordinary skill in the art to provide the method of Mann in order to diagnose Van Moorsel’s patients for the presence of SARS-CoV-2 (COVID-19) because Mann teaches that overexpression of LY6E IFIT1 OASL IFI27, CCL2, LAMP3 RSAD2 GBP1 ISF15 IFIT5 DDX58 ATF3 SEPT4 is associated with viral infection (see paragraph [0022]) and because van Moorsel teaches an association of certain gene expression with SARS-CoV-2 infection in patients.
Regarding present claims 11, 12. Mann et al. does not expressly teach normalizing the gene expression products, entering the normalized gene product expression values into SARS-CoV-2 infection classifier or calculating the presence of an etiology probability or the method of generating the classifier, in claim 12. It is noted that the step of normalizing the gene expression product has been addressed in the rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph above. The Examiner’s interpretation of this step is that the detected expression the genes in question is considered in determination of the presence or absence of the viral infection. This and the other method steps, regarding the generation of the classifier, would have been prima facie obvious as they read on the method steps of measuring the expression levels of one or more genes selected from USP18, MAP2K6, ATF3, BCL2L14, CCL2, CCL8, CXCL10, DDX58, GBP1P1, HERC6, IFIH1, IFIT2, LAMP3, OAS2, PANK2, PML, PNPT1, TDRD7, and TOR1B, taught in Mann.
Regarding present claim 14. The steps of entering the normalized gene product expression values into one or more additional classifier(s) selected from a non-COVID-19 viral infection classifier, a bacterial infection classifier, a non-infectious illness classifier, and a healthy subjects classifier, said classifier(s) comprising pre-defined weighted values for each of the gene products of the plurality of pre- determined gene products for the platform, optionally wherein said classifier(s) is retrieved from one or more databases; and (g) calculating a presence or an etiology probability for the one or more additional classifier(s) based upon said normalized expression values, would have been prima facie obvious to the person of ordinary skill in the art as they read on merely providing the control value for determination of the gene expression.
Regarding present claims 15 and 18. Mann teaches an influenza virus infection associated with increased expression levels of USP18, MAP2K6, ATF3, BCL2L14, CCL2, CCL8, CXCL10, DDX58, GBP1P1, HERC6, IFIH1, IFIT2, LAMP3, OAS2, PANK2, PML, PNPT1, TDRD7, and TOR1B and teaches monitoring the subject’s response to the antiviral therapy (see page 17, paragraph [0084], page 24, paragraph [00141], Figure 16, Table 1).
Thus, the present claims would have been prima facie obvious at the time of the present invention.
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable and obvious over Mann et al. (WO 2018/154075 in IDS on 12/6/2022) in view of van Moorsel et al. (Frontiers in Medicine, May 16, 2020, p. 1-8) as applied to claim 11 and further in view of Ko et al. (International Journal of Antimicrobial Agents March 2020, p. 1-3).
Mann and van Moorsel teach the claimed invention as discussed above. They do not teach administering to the subject drug or other antiviral therapy.
Ko et al. teach a method of treating coronavirus infection comprising administering remdesivir (see page 2). Ko et al. teach clinical efficacy and tolerance of remdesivir in patients infected with SARS-CoV-2 (see page 2).
It would have been prima facie obvious to the person of ordinary skill in the art to provide the method of Mann and Van Morse and to subsequently treat the patient, infected with a coronavirus, with remdesivir because Ko et al. teach clinical efficacy and tolerance of remdesivir in patients infected with SARS-CoV-2 (see page 2).
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648