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 .
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.
Status of the Claims
Claims 5-17, 49, 50, 58, 59, 61, 67, and 77 are pending and examined herein.
Priority
This application, 18/693,210, filed 03/19/2024, is a 371 of PCT/US2022/045989 filed on 10/07/2022, and claims benefit of provisional application 63/253,509 filed on 10/07/2021. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 10/07/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 03/19/2024 is acknowledged and has been considered.
Claim Objections
Claims 67 and 77 are objected to because of the following informalities:
Claim 67 recites “…(AUC) of 0.62, 0.67, 0.68, 0.68…”. The claim is objected to due to the duplicate recitation of the value “0.68”.
Claim 77 recites “…specifically binds to a protein each protein capture reagent of the set has…” and is objected due to the recitation of “protein each protein” rather than “protein wherein each protein”.
Additionally, claim 77 recites “…comprising N a set of protein capture reagents…” and is objected to due to the use of incorrect grammar.
Appropriate correction is required.
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the method of measuring proteins selected from the group consisting of PSP-94, MMP-12, SP-D, HE4, PH, FUT5 and CRLF1 in a human sample using a set of capture reagents must be shown or the feature(s) canceled from the claim(s). The drawings currently represent relationships between lung cancer risk and smoking behavior, which is not embodied by the claims. The measurement of the recited proteins is not represented. No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 67 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.
Claim 67 recites “...the method provides an area under the curve (AUC) of 0.62, 0.67…”. The claim is indefinite because it is unclear how the method of claim 5 can “provide” a specific AUC value, e.g. how could the method be performed in in a way so that the data output results in those specific AUC values recited in the claim, especially considering there is no curve generating step recited in the claim 67 or claim 5 from which it depends.
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 67 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claim 67 recites “The method of claim 5, wherein the method provides an area under the curve (AUC) of 0.62, 0.67, 0.68, 0.68, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, or above”.
The claim is directed to a judicial exception, mainly abstract ideas, specifically, a mathematical calculation. This judicial exception is not integrated into a practical application because there is no practical application recited in the claims such as performing a treatment in a way that is particular, and not merely instructions to "apply" the exception in a generic way. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps amount to mere data gathering that does not go beyond well-understood, routine, and conventional activity; as detailed below.
Step 1 – Whether a claim is to a statutory category - YES
The invention of claim 67 is directed to a method of measuring a set of proteins by contacting a sample from a human subject with a set of capture reagents that have an affinity for a different protein of the set of proteins comprising PSP-94 protein, and at least one, two, three, four, five, or six proteins selected from the group consisting of MMP-12, SP-D, HE4, PH, FUT5 and CRLF1, and providing an area under the curve (AUC) of 0.62, 0.67, 0.68, 0.68, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, or above. Therefore, the instantly claimed invention falls into one of the four statutory categories.
Step 2A Prong 1 – Whether the claim is directed to a judicial exception (i.e. Does the claim recite an abstract idea, law of nature, or natural phenomenon?) - YES
Claim 67 recites the following steps which fall under a mathematical calculation of the abstract ideas grouping:
Claim 67 discloses a method of measuring a set of proteins by contacting a sample from a human subject with a set of capture reagents that have an affinity for a different protein of the set of proteins comprising PSP-94 protein, and at least one, two, three, four, five, or six proteins selected from the group consisting of MMP-12, SP-D, HE4, PH, FUT5 and CRLF1, and providing an area under the curve (AUC) of 0.62, 0.67, 0.68, 0.68, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, or above. The broadest reasonable interpretation of this step is measuring the level of PSP-94 and at least one of the other proteins in the human sample using the appropriate capture reagents, and using the data from those measurements to determine/provide an AUC that is specifically one of the values recited in the claim or above. This limitation recites a mathematical calculation which is a judicial exception, because it is merely using the data of protein measurements to “provide” and AUC value, which would inherently require a mathematical operation to be made based on known methods in the art.
The MPEP defines a mathematical calculation as a mathematical operation (such as multiplication) or an act of calculating using mathematical methods to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation. There is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation. See MPEP 2106.04(a)(2). Therefore, while claim 67 uses the claim language “provides”, it is still considered a mathematical calculation as the determination of AUC inherently requires it. The methods routinely used in the art to determine AUC values all use a mathematical operation such as multiplication or division.
Regarding the identification of mathematical calculation abstract ideas, the courts have held similar claims to be mathematical calculation, as In re Abele, 684 F.2d 902, 903, 214 USPQ 682, 683-84 (CCPA 1982), which involved claims to calculate the difference between local and average data values.
Thus, claim 67 falls into a judicial exception.
Step 2A: Prong 2 - Does the claim recite additional elements that integrate the judicial exception into a practical application? The Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception.
Claim 67 does not recite any additional element that integrate the exception into a practical application of the exception. The claim also recites the additional steps of measuring proteins with capture reagents, which are insufficient to integrate the exception into a practical application because the purpose is merely to obtain data to perform the mathematical calculation step. It is thus extra-solution activity, and does not integrate the judicial exception into a practical application.
In particular, of the claims indicated in the rejection heading, none of the additionally recited limitations amount to an additional element or combination of elements that apply, rely on, or use the judicial exceptions in a manner that impose meaningful limit on the judicial exceptions.
Step 2B; Whether the additional elements contribute an “inventive concept”. In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05.
Briefly, claim 67 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because of the following reasons. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, has been found to be insufficient to add “significantly more” (MPEP 2106.05(I)(A)).
The additional steps of measuring a set of proteins by contacting a sample from a human subject with a set of capture reagents that have an affinity for a different protein of the set of proteins comprising PSP-94 protein, and at least one, two, three, four, five, or six proteins selected from the group consisting of MMP-12, SP-D, HE4, PH, FUT5 and CRLF1, do not add a meaningful limitation to the instant method as they would have been routinely used by those of ordinary skill in the art as supported by Sun et al. (2018). “Genomic atlas of the human plasma proteome”. Nature, 558(7708), 73-79, (herein referred to as Sun), and Hellstrom et al. (2003). “The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma”. Cancer research, 63(13), 3695-3700, (herein referred to as Hellstrom).
Sun teaches the creation of a genetic atlas of the human plasma proteome, using an expanded version of an aptamer-based multiplex protein assay (SOMAscan) to quantify 3,622 plasma proteins, and linking genetic variation with biological pathway, disease, and drug databases (abstract; page 73, column 1, 2nd paragraph). Sun teaches the use of a multiplexed, aptamer-based approach (SOMAscan assay) to measure the relative concentrations of 3,622 plasma proteins or protein complexes assayed using 4,034 modified aptamers (page 80, column 1, 3rd paragraph). More specifically, Sun teaches the measurement of the PSP-94 (Beta-microseminoprotein), MMP-12 (Macrophage metalloelastase), SP-D (Pulmonary surfactant-associated protein D), HE4 (WAP four-disulfide core domain protein 2), PH (Pancreatic hormone), FUT5 (Alpha-(1,3)-fucosyltransferase 5), and CRLF1 (Cytokine receptor-like factor 1) proteins in samples (Supplementary Table 18). Sun teaches that for protein measurements, modified single- stranded DNA SOMAmers are used to bind to specific protein targets that are then quantified using a DNA microarray, then protein concentrations are quantified as relative fluorescent units (page 80, column 1, 4th paragraph).
Hellstrom teaches experiments used to explore whether quantitation of HE4 protein levels in serum can be used as a biomarker for ovarian carcinoma (abstract). Additionally, Hellstrom teaches AUC values for HE4 and CA 125 for discriminating between cases and various controls (Table 2), and that the ROC curves displayed have the following AUC: (a) HE4 = 0.96, CA125 = 0.95 (Fig. 4) and (b) HE4 = 0.85, CA125 0.9 (page 3698, column 1, 1st paragraph; Fig. 5). Hellstrom teaches that it is also common to summarize an ROC curve by the AUC, and that a perfect ROC curve has AUC 1 (or 0), and a useless marker has AUC 0.5 (page 3698, column 2, 1st full paragraph).
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to a law of nature and abstract idea without significantly more. For additional guidance, applicant is directed generally to MPEP § 2106.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 5-17, 49, 50, 58, 59, and 61 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun et al. (2018). “Genomic atlas of the human plasma proteome”. Nature, 558(7708), 73-79, (herein referred to as Sun).
Regarding claims 5-17, 49, 50, 58, 59, and 61, Sun teaches the creation of a genetic atlas of the human plasma proteome, using an expanded version of an aptamer-based multiplex protein assay (SOMAscan) to quantify 3,622 plasma proteins, and linking genetic variation with biological pathway, disease, and drug databases (abstract; page 73, column 1, 2nd paragraph). Sun teaches that the study consisted of about 50,000 participants nested within a randomized trial of varying blood donation intervals, with the blood samples for research purposes collected in 6-ml EDTA tubes using standard venipuncture protocols (page 80, column 1, 2nd paragraph). More specifically, Sun teaches the use of a multiplexed, aptamer-based approach (SOMAscan assay) to measure the relative concentrations of 3,622 plasma proteins or protein complexes assayed using 4,034 modified aptamers (page 80, column 1, 3rd paragraph). More specifically, Sun teaches the measurement of the PSP-94 (Beta-microseminoprotein), MMP-12 (Macrophage metalloelastase), SP-D (Pulmonary surfactant-associated protein D), HE4 (WAP four-disulfide core domain protein 2), PH (Pancreatic hormone), FUT5 (Alpha-(1,3)-fucosyltransferase 5), and CRLF1 (Cytokine receptor-like factor 1) proteins in samples (Supplementary Table 18). Sun teaches that for protein measurements, modified single- stranded DNA SOMAmers are used to bind to specific protein targets that are then quantified using a DNA microarray, then protein concentrations are quantified as relative fluorescent units (page 80, column 1, 4th paragraph). Sun teaches that by linking genetic factors to diseases via specific proteins, the analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development (abstract).
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.
Claim 67 is rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 5-17, 49, 50, 58, 59, and 61 above, in view of Hellstrom et al. (2003). “The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma”. Cancer research, 63(13), 3695-3700, (herein referred to as Hellstrom).
The teachings of Sun are incorporated herein.
Regarding claim 67, Sun teaches all the limitations of claim 5 of the instant application but does not specifically teach that the method provides an area under the curve (AUC) of 0.62, 0.67, 0.68, 0.68, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, or above.
Hellstrom teaches experiments used to explore whether quantitation of HE4 protein levels in serum can be used as a biomarker for ovarian carcinoma (abstract). Hellstrom teaches that their findings indicate that the HE4-based ELISA can aid the diagnosis of ovarian carcinoma and that it has an advantage over the classical CA125 test by being less frequently positive in women who have benign disease (page 3696, column 1, 1st full paragraph). Additionally, Hellstrom teaches AUC values for HE4 and CA 125 for discriminating between cases and various controls (Table 2), and that the ROC curves displayed have the following AUC: (a) HE4 = 0.96, CA125 = 0.95 (Fig. 4) and (b) HE4 = 0.85, CA125 0.9 (page 3698, column 1, 1st paragraph; Fig. 5). Hellstrom teaches that it is also common to summarize an ROC curve by the AUC, and that a perfect ROC curve has AUC 1 (or 0), and a useless marker has AUC 0.5 (page 3698, column 2, 1st full paragraph).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the protein measurement method recited in Sun to provide an AUC value that is greater than 0.76, as taught by Hellstrom, as a matter of combining prior art methods to yield predictable results. Sun and Hellstrom are both in the same field of measuring proteins in the context of disease biomarkers, and overlap the in the proteins measured, which is HE4. Furthermore, Hellstrom teaches that it is also common to summarize an ROC curve by the AUC, indicating that it is a method that is a well-understood, routine, and conventional activity in the art. Like Hellstrom, Sun has data on protein levels as well as the disease presence of patients, and it would be only a matter of using that data in the method of Sun to have the predictable result of creating ROC curves and generate AUC scores for identifying patients with a disease from those that are healthy. Additionally, it would have been obvious to person of ordinary skill in the art to have an AUC of 0.62, 0.67, 0.68, 0.68, 0.70, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, or above, because Hellstrom teaches that a perfect ROC curve has AUC 1 (or 0), and a useless marker has AUC 0.5.
Claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over Sun in view of Zuk et al. (U.S. Patent No. 4208479).
While Sun makes obvious the method of claims 5-17, 49, 50, 58, 59, and 61 as discussed above, they do not recite all the reagents together in a kit.
However, Zuk et al. teaches the convenience and accuracy enhancement associated with combining all necessary reagents for an assay together in a kit (column 22, lines 20-68).
Therefore, it would have been obvious to one of ordinary skill in the art to assemble together the reagents (protein capture reagents that specifically binds to a protein, etc.) in the form of a kit, in order to create an assay kit to measure one or more of PSP-94, MMP-12, SP-D, HE4, PH, FUT5 or CRLF1 proteins in a sample from a human subject as described by Sun. A skilled artisan would have been motivated to combine all necessary reagents together in a kit, because kits are well known as being convenient and economical. A person of ordinary skill would have had a reasonable expectation of success in in assembling the reagents of the patented claims into kits as taught by Zuk because the creation and use of kits is a practice that is well-understood, routine and conventional in the field.
Conclusion
For all the reasons discussed above, claims 5-17, 49, 50, 58, 59, 61, 67, and 77 are rejected and therefore no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER JOSEPH HOFFMAN whose telephone number is (571)272-9080. The examiner can normally be reached 10:00-6:30 M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached at (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER J. HOFFMAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 3, 2026
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