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 Claims
Claims 1, 3, 5-14 and 16-20 are pending and under examination.
Election/Restrictions
Applicant’s election without traverse of species CYR61 and PTX3 in the reply filed on 03/02/2026 is acknowledged.
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, 3, 5-14 and 16-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1: The instantly claimed invention is directed a method comprising: obtaining a sample comprising blood from a subject, and determining a level of at least 2 biomarkers. Therefore, the instantly claimed invention falls into one of the four statutory categories. (Step 1: YES)
ELIGIBILITY STEP 2A; WHETHER A CALIM IS DIRECTED TO A JUDICIAL EXCEPTION. First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A Prong 1
Claim 1 recites the following steps which fall under the mental processes of abstract ideas and nature/natural phenomena:
In particular, claim 1 is drawn to obtaining a sample comprising blood from a subject, and determining a level of at least 2 biomarkers in the sample. The limitations of a sample comprising blood from a subject, and determining a level of at least 2 biomarkers in the sample are directed to a judicial exception because the claim language clearly conveys the naturally occurring relationship between blood samples from a subject and the level of biomarkers in said blood. This constitutes law of nature/natural phenomena, as a natural correlation between the level of the biomarkers in blood from a subject.
Additionally, the step of determining a level of at least 2 biomarkers may be categorized as abstract ideas, namely mental processes/ concepts performed in the human mind (such as a person simply thinking about the level of biomarkers). Such step would read on purely mental activity such as a practitioner looking at a subject’s chart and thinking about the level of said biomarkers.
Claim 3 recites limitations related to the natural products for the natural correlation between the level of biomarkers and blood from a subject.
Claim 5 recites the mathematical concept of calculating a score from the subject based on the level of the biomarker. Also, the claim can be mental processes performed in the human mind. Similarly, claim 6 recites limitations directed to calculating a score, comparing the score, and identifying a subject who has a score that is comparable to the reference are considered mathematical concepts and mental processes. Thus, the claims are directed to abstract ideas. Claims 7-8 and 9 recite limitations directed to recommending the subject for additional evaluation wherein the evaluation comprises imaging and/or biopsy and wherein the treatment comprises chemotherapy, hormone, therapy, immunotherapy, radiation, or surgical resection are directed to mental processes. Claims 11-12 recite determining a level of biomarkers comprises using digital ELISA; Meso Scale Discovery (MSD); Single-Molecule Counting (SMC); LUMINEX; SOMAscan Assays; mass spectrometry (optionally MALDI-MS), and/or mass cytometry (optionally CyTOF) and wherein the digital ELISA uses Single-Molecule Arrays (SIMOA) are directed to mental processes/ concepts performed in the human mind. The limitations that follow the wherein clauses are not the same as active steps.
Similarly, independent claim 13 recites the following steps which fall under the mental processes of abstract ideas and nature/natural phenomena:
In particular, claim 13 is drawn to obtaining a sample comprising blood from a subject, and determining a level of at least 2 biomarkers in the sample. The limitations of a sample comprising blood from a subject, and determining a level of at least 2 biomarkers in the sample are directed to a judicial exception because the claim language clearly conveys the naturally occurring relationship between blood samples from a subject and the level of biomarkers in said blood. This constitutes law of nature/natural phenomena, as a natural correlation between the level of the biomarkers in blood from a subject. The step of determining a level of at least 2 biomarkers may be categorized as abstract ideas, namely mental processes/ concepts performed in the human mind (such as a person simply thinking about the level of biomarkers). Such step would read on purely mental activity such as a practitioner looking at a subject’s chart and thinking about the level of said biomarkers. Furthermore, the claim recites the mathematical concept of calculating a score from the subject based on the level of the biomarker. Also, the claim can be mental processes performed in the human mind. The claim also recites limitations directed to identifying a subject who has a score above a threshold score and recommending the subject for additional evaluation are considered mental processes. Thus, the claims are directed to abstract ideas.
Claim 14 recites limitations related to the natural products for the natural correlation between the level of biomarkers and blood from a subject. Claim 16 recites limitations directed to calculating a score, comparing the score, and identifying a subject who has a score that is comparable to the reference are considered mathematical concepts and mental processes. Thus, the claims are directed to abstract ideas. Claims 17 recites limitations directed to recommending the subject for additional evaluation wherein the evaluation comprises imaging and/or biopsy are directed to mental processes. Claims 19-20 recite determining a level of biomarkers comprises using digital ELISA; Meso Scale Discovery (MSD); Single-Molecule Counting (SMC); LUMINEX; SOMAscan Assays; mass spectrometry (optionally MALDI-MS), and/or mass cytometry (optionally CyTOF) and wherein the digital ELISA uses Single-Molecule Arrays (SIMOA) are directed to mental processes/ concepts performed in the human mind. The limitations that follow the wherein clauses are not the same as active steps. (Step 2A, Prong 1: YES).
Step 2A: Prong 2:
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. Besides the abstract ideas, claims 1, 9-10, 13 and 18 recite obtaining a sample comprising blood from a subject, administering a treatment for breast cancer to the subject wherein the treatment comprises chemotherapy, hormone therapy, immunotherapy radiation, or surgical resection. When so evaluated, these additional elements represent mere data gathering that is necessary for use of the recited judicial exception and is recited at a high level of generality. In particular, these limitations are insignificant extra-solution activity to obtain data information for treatment. The additional element of administering said treatment does not integrate the recited judicial exception into a practical application for the following reasons. Although this limitation indicates that a treatment of any chemotherapy, hormone therapy, immunotherapy radiation, or surgical resection is to be administered, it does not provide any information as to how the patient is to be treated or what the treatment is but instead covers a generic possibility that may not be relevant to the disease. In fact, this limitation is recited at such a high level of generality. The administering step does not apply or use the judicial exception in a meaningful way. These judicial exceptions are not integrated into a practical application for the following reasons.
Claims 8 and 17 recite limitations that are directed to limitations necessary to perform the recited judicial exception. When so evaluated, these additional elements represent mere data gathering that is necessary for use of the recited judicial exception and is recited at a high level of generality. This judicial exception is not integrated into a practical application for the following reasons. (Step 2A, Prong 2: NO).
Step 2B: In step 2B, it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05. The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception. The additional limitations in claims 1, 8-10, 13 and 17-18 are well-understood, routine, and conventional.
Walt (US2018/0149653 A1, published 05/31/2018) teaches detecting breast cancer in a subject having altered levels of CA 15-3, CA 19-9, CDKN2D, CYR61, ER alpha, HER2, PR, and/or VEGF in a plasma or serum sample of the subject (see para. [0086]). Walter teaches the breast cancer and healthy serum samples were tested for eight different markers (see Fig. 2) and the box plots reflect the samples above the calculated limit of detection for the assay (see para. [0119]). Walter teaches the array images are analyzed and decoded based on activity and bead type (see para. [0156]). Walt teaches using digital ELISA (see para. [0061]). Walter further teaches SIMOA (see para. [0062]).
Spetzler (US20140148350A1, published 05/29/2014) teaches biomarkers can be assessed for diagnostic, therapy-related or prognostic methods to identify phenotypes, such as a condition or disease, or the stage or progression of a disease (see abstract). Spetzler teaches the method of characterizing a cancer in a subject comprising a biological sample that comprises blood (see para. [0010]). Spetzler teaches cancer treatments are chemotherapy, radiation therapy, or surgery (see para. [0394]). Spetzler teaches mass spectrometry (see para. [0329]).
Therefore, these additional elements when viewed alone and in combination are not sufficient to amount to significantly more than the recited judicial exception. When taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. (Step 2B: NO).
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 1, 3, 5-14 and 16-20 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 13 recite “biomarkers as listed in Table A in the sample” is unclear to the metes and bounds of the claim. There is no limit to the length of a claim. If the subject matter (i.e., Table A) can be listed in the specification, that list can be copied and pasted into a claim. "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)" (MPEP 2173.05(s)). Because the biomarkers have not been defined in the claims, the claims are interpreted to have at least 2 of any biomarkers.
Additionally, the recitation of “a level of at least 2” biomarkers is unclear to how many levels are being determined in the method, as the claim requires at least 2 biomarkers. Are these biomarkers being measured together to have one level for determination or each biomarker is separately determined? Claims 3, 5-12, 14 and 16-20 are rejected as being dependent from claims 1 and 13.
Regarding claims 11 and 19, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation “mass spectrometry” and “ mass cytometry”, and the claim also recites “(optionally MALDI-MS)” and “(optionally Cy TOF)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
Claims 1, 3, 5-9, 11-13, 16-17 and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Walt et al. (US2018/0149653 A1, published 05/31/2018).
With respect to claims 1 and 13, Walt teaches detecting breast cancer in a subject having altered levels of CA 15-3, CA 19-9, CDKN2D, CYR61, ER alpha, HER2, PR, and/or VEGF in a plasma or serum sample of the subject (see para. [0086]). Walter teaches the breast cancer and healthy serum samples were tested for eight different markers (see Fig. 2) and the box plots reflect the samples above the calculated limit of detection for the assay (see para. [0119]). Walter teaches a predictive signature for early-stage cancer and subtype-specific expression was also examined to compare hormone receptor (HR+) cancer and TNBC samples (see paras. [0121]-[0122]). Walter teaches all of the data obtained for these serum samples were used as inputs to evaluate the combined utility of eight protein markers and patient age toward a breast cancer diagnostic signature (see para. [0139]).
With respect to claim 5, Walter teaches the breast cancer and healthy serum samples were tested for eight different markers (see Fig. 2) and the box plots reflect the samples above the calculated limit of detection for the assay (see para. [0119]).
With respect to claims 6 and 16, Walter teaches a predictive signature for early-stage cancer and subtype-specific expression was also examined to compare hormone receptor (HR+) cancer and TNBC samples (see paras. [0121]-[0122]).
With respect to claims 7 and 17, Walter teaches all of the data obtained for these serum samples were used as inputs to evaluate the combined utility of eight protein markers and patient age toward a breast cancer diagnostic signature (see para. [0139]).
With respect to claim 8, Walter teaches the array images are analyzed and decoded based on activity and bead type (see para. [0156]).
With respect to claim 9, Walter teaches treatment of a subject having breast cancer or a propensity to develop such a condition can be monitored using the methods and compositions of the invention (see para. [0112]).
With respect to claims 11-12 and 19-20, Walt teaches using digital ELISA (see para. [0061]). Walter further teaches SIMOA (see para. [0062]).
Claims 1, 3, 5-11, 13-14 and 16-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Spetzler et al. (US20140148350A1, published 05/29/2014).
With respect to claims 1, 3, and 13-14, Spetzler teaches biomarkers can be assessed for diagnostic, therapy-related or prognostic methods to identify phenotypes, such as a condition or disease, or the stage or progression of a disease (see abstract). Spetzler teaches the method of characterizing a cancer in a subject comprising a biological sample that comprises blood (see para. [0010]). Spetzler teaches determining a level of one or more additional biomarker and comparing the level of the one or more additional biomarker to a reference in order to characterize the cancer and the biomarkers are HSP70, CD81, ERB4…etc. (see para. [0023]). Spetzler also teaches CYR61 (elected species) biomarker (see para. [1089]). Spetzler teaches biomarkers for characterizing a breast cancer is, for example, FOXML PRAME, STK15, CEGP1, HER2, HER3, CYP3A4 (see para. [0772]). Spetzler also teaches biomarker for breast cancer disorder is PTX3 (elected species) (see bottom of Table 7). Spetzler teaches a median correlation coefficient can be calculated for the biomarker and the biomarker identified for use in determining the sensitivity of a subject to the treatment if the median correlation coefficient exceeds about 0.3 (see para. [1184]). Thus, Spetzler teaches the elected species.
With respect to claims 5-8, and 16-17, Spetzler teaches a median correlation coefficient can be calculated for the biomarker and the biomarker identified for use in determining the sensitivity of a subject to the treatment if the median correlation coefficient exceeds about 0.3 (see para. [1184]). Spetzler teaches analysis of the bodily fluid can aid in determining whether a tissue biopsy should be obtained (see para. [0185]). Spetzler teaches a phenotype can also be a clinically distinct type or subtype of a condition or disease (see para. [0164]).
With respect to claims 9-10 and 18, Spetzler teaches cancer treatments are chemotherapy, radiation therapy, or surgery (see para. [0394]).
With respect to claims 11 and 19, Spetzler teaches mass spectrometry (see para. [0329]).
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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