DETAILED ACTION
Claims 1-20 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 06/07/2024 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.
1. Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed method is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 1
This part of the eligibility analysis evaluates whether the claim falls within any statutory
category per MPEP 2106.03
Regarding instant claims 1-20, Example 43 of “2019 PEG” is particularly enlightening because the fact pattern of claim 1 of example 43 is most similar to the instant application claims 1-20.
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 1, the claim is
directed to a process, which is one of the statutory categories of invention as the claim recites
“A treatment method comprising: (a) calculating a ratio of C11 to C13 levels measured in a
blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3)
to identify the patient as having a non-responder phenotype; (b) administering a treatment to the
patient having a non-responder phenotype.” (Step 1: YES).
Similarly, instant claims 1-20 are directed to a statutory method that measures naturally occurring protein biomarker MAGE-A4 and correlating the levels of naturally occurring MAGE-A4 with tumor intensity and the diagnosis of a tumor or cancer (step 1: YES).
Step 2A, Prong 1: Does the claim recite a judicial exception?
This part of the eligibility analysis evaluates whether the claim recites a judicial
exception. As explained in MPEP 2106.04(II) and the October 2019 Update, a claim “recites” a
judicial exception when the judicial exception is “set forth” or “described” in the claim.
Regarding instant claims 1-20, Example 43 of the “2019 PEG” shows a similar fact pattern.
Regarding claim 1 in Example 43 of the “2019 PEG” and per Step 2A, prong 1, the claim recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3)
to identify the patient as having a non-responder phenotype,” and according to broadest
reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the
ratio of C11 to C13 that can be used to identify whether the patient has the non-respondent
phenotype.
Specifically, limitation (a) in claim 1 of Example 43 of the “2019 PEG” recites “calculating
a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic
Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder
phenotype,” which has a BRI that requires performing an arithmetic calculation (division) in
order to obtain the ratio of C11 to C13 levels, and then using this ratio to identify whether the
patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or
greater and thus is not responding, or will not respond, to glucocorticoids). This limitation
therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the
2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG
Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping
of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be
practically performed in the human mind, and is in fact performed in the human mind on a daily
basis, for instance by school-aged children studying mathematics. Note that even if most
humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them
complete the recited calculation, the use of such physical aid does not negate the mental nature
of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract
ideas.
In addition, limitation (a) describes a naturally occurring relationship between the ratio
of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a
law of nature. Accordingly, limitation (a) recites a judicial exception (an abstract idea that falls
within the mathematical concept and mental process groupings in the “2019 PEG”, and a law of nature), and the analysis must therefore proceed to Step 2A Prong Two.
Similarly, instant claims 1-20 recite measuring protein biomarker MAGE-A4 and correlating the measurement of MAGE-A4 with the diagnosis of a tumor or cancer, and thus is considered a law of nature. Further, claims 1-20 recite “determining a MAGE-A4 tumor intensity proportion score (MAGE-A4 TIPS), wherein the MAGE-A4 TIPS is the number of MAGE-A4 staining viable tumor or cancer cells found in the tissue sample divided by the total number of staining and non-staining viable tumor or cancer cells, multiplied by 100”, which has a BRI that requires performing an arithmetic calculation (division and multiplication) in order to obtain the TIPS value. This limitation therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping of abstract ideas. In addition, this type of simple arithmetic calculation (division/multiplication) can be practically performed in the human mind, and is in fact performed in the human mind on a daily basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract ideas.
Accordingly, instant claims 1-20 recite a judicial exception (a law of nature and an abstract idea that falls within the mental process grouping) and the analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
Regarding instant claims 1-20, Example 43 of “2019 PEG” shows a similar fact pattern.
In claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. Besides the abstract idea, the claim 1 of example 43 of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient having a non-responder phenotype”. Although this limitation indicates that a treatment 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 any possible treatment that a doctor decides to administer to the patient. In fact, this limitation is recited at such a high level of generality that it does not even require a doctor to take the calculation step’s outcome (the patient’s phenotype) into account when deciding which treatment to administer, making the limitation’s inclusion in this claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception.
Similarly, instant claims 1-20 do not have additional elements that would integrate the judicial exception cited above into a practical application. Instant claims 16-17 recites “if the tissue sample is determined or scored to have a high or diagnostically positive MAGE-A4 score, the patient is treated with a cancer therapeutic to which the patient is likely to respond favorably”. Instant claim 18 recites “wherein the cancer therapeutic comprises administration to the patient an anti-cancer drug or an anti-cancer therapy, and optionally the anti-cancer therapy comprises an immunotherapy, a monoclonal antibody therapy, an adoptive cell therapy (ACT), a T-cell receptor (TCR) therapy, or a chimeric antigen receptor (CAR) T-cell therapy”. Like example 43 where the general treatment was found lacking any significance and at best was equivalent to adding the words “apply it” to the judicial exception. The recitation of an anti-cancer drug or an anti-cancer therapy and the therapy being comprises an immunotherapy, a monoclonal antibody therapy, an adoptive cell therapy (ACT), a T-cell receptor (TCR) therapy, or a chimeric antigen receptor (CAR) T-cell therapy is broad and considered a general treatment. Example 43 failed with a general treatment step, and like Example 43, instant claims 1-20 recite a general treatment.
Therefore, instant claims 1-20 do not integrate the judicial exception into a practical application.
Step 2B: Does the claim recite significantly more?
Regarding instant claims 1-20, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claims do not recite any active steps. While instant claims 16-18 recite “treating” and “administering”, it does not add significantly more and is equivalent to just “applying” a treatment. Accordingly, instant claims 1-20 are not eligible (Step 2B: NO).
Thus, instant claims 1-20 are rejected under 35 USC 101.
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.
2.Claims 1-5, 8-13, and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Verardo et al., US20240295559A1 (effectively filed on 09/08/2021), in view of Williams et al., US20200400674A1 (IDS filed on 06/07/2024).
Verardo teaches an immunohistochemistry (IHC) method for determining and scoring the extent of cellular expression of a biomarker in a tissue sample (see claims 1-2 of Verardo), comprising:
(a) staining a tissue sample with an antibody which specifically binds to a biomarker (see claims 1-2 of Verardo);
(b) determining a total number of viable tumor or cancer cells having the biomarker staining, and determining a total number of staining and non-staining viable tumor or cancer cells in at least a portion of the tissue sample (see claim 2 of Verardo),
wherein a tumor or cancer cell is counted as positively stained with an antibody if there is cytoplasmic and/or nuclear biomarker staining at any intensity above a defined threshold (see claim 15 of Verardo); and
(c) determining a tumor intensity proportion score (TIPS),
wherein the TIPS is the number of biomarker staining viable tumor or cancer cells found in the tissue sample divided by the total number of staining and non-staining viable tumor or cancer cells, multiplied by 100 (see claim 2 of Verardo) (instant claims 1 and 20).
Verardo teaches wherein the defined threshold comprises:
a 1+ positive staining intensity evaluated at a high magnification (see [0205], see claim 13 of Verardo); a 2+ positive staining intensity evaluated at a medium magnification (see [0206], see [0140]); or a 3+ positive staining intensity evaluated at a low magnification (see [0207], see [0200]) (instant claim 2). Verardo teaches the section or portion of the tissue sample is prepared and stained on a slide and the slide comprises a formalin=fixed paraffin embedded specimen (see [0008]) (instant claims 10 and 13). Verardo teaches the magnification being at least about 4x, 10x, 20x, and 40x (see [0140] “In alternative embodiments, for evaluation of the immunohistochemical staining and scoring, an objective of 10-40× magnification is appropriate. In alternative embodiments, convincing nuclear staining of tumor cells with 1+ intensity or higher is included in the scoring. In alternative embodiments, the lower limit of 1+ positivity is evaluated using a high power (for example, 40×) objective”, see [0008], see [0170] “FIG. 3 illustrates positive in-house control tissue stained with exemplary Ki-67 IHC showing different intensities of nuclear Ki-67 expression by invasive breast carcinoma cells (20× magnification).”, see claim 13 of ‘559) (instant claim 3). Verardo teaches dividing the number of viable tumor or cancer cells staining at a 2+ or a 1+ or greater positive staining intensity divided by the total number of staining and non-staining viable tumor or cancer cells, multiplied by 100 (see [0008], see [0036], see [0206], see [0208]) (instant claims 4-5). Verardo teaches the marker TIPS of about 5% or greater indicates a positive diagnostic status of the tissue sample and the marker stains at a 1+ or greater positive staining intensity (see [0008], see [0303]) (instant claims 8-9 and 16). Verardo teaches scoring the biomarker by using tumor intensity proportion score (see claim 2 of Verardo) (instant claims 19-20).
Verardo does not teach determining the expression of Melanoma Associated Antigen Gene-A4 (MAGE- A4) in a tissue sample, or the use of anti-MAGE-A4 antibody.
Williams teaches a method of using IHC to measure MAGE-A4 expression in a tissue sample to diagnose a subject with cancer (see claim 1 of ‘674, see [0001] – [0002], see [0023] – [0024]) (instant claims 1-2, 4-5, 8-10, 13, and 20). Williams teaches wherein the antibody comprises a monoclonal mouse anti-MAGE-A4 antibody OTI1F9 (see [0011], see [0013]) (instant claims 11-12). Williams teaches a method for treating or ameliorating a tumor or a cancer in a patient, comprising determining the amount of MAGE-A4 in a tissue sample (see abstract, see [0002]), wherein if the tissue sample is determined or scored to have a high or a diagnostically positive MAGE-A4 score (see [0076]), the patient is treated with a monoclonal antibody therapy (see [0049], see [0052]) (instant claims 16 and 18). Williams teaches the cancer or tumor being head and neck, lung, non-small cell lung cancer, gastric, ovarian, melanoma, urothelial, and/or colorectal (see [0053]) (instant claims 15 and 17). Williams teaches the use of a kit with an antibody that specifically binds to MAGE-A4 (see [0049], see claim 20 of Williams) (instant claim 19).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the method of assessing biomarker expression in a tumor or cancer taught by Verardo with the method of measuring MAGE-A4 expression in tissue and treating cancer with anti-MAGE-A4 antibodies taught by Williams. Williams provides motivation for substituting the biomarker of Verardo with the MAGE-A4 biomarker of Williams by teaching that MAGE-A4 is a tumor-associated antigen belonging to the MAGE family of germline encoded cancer antigen and is the ideal target for therapeutic intervention and a high level of expression of MAGE-A4 has been reported in tumors (see [0002]). Williams further provides motivation by teaching that detecting expression of MAGEA4 in patients tumor samples provides a convenient diagnostic approach to classify patients as likely responders and therefore eligible for treatment of the corresponding therapy (see [0004]). The artisan would have reasonable expectation of success based on the cumulative disclosures of these prior art references.
3. Claims 6-7 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Verardo and Williams et al., as it pertains to claims 1-5, 8-13, and 15-20 above, in view of Cooper, Wendy A et al. “Intra- and Interobserver Reproducibility Assessment of PD-L1 Biomarker in Non-Small Cell Lung Cancer.” Clinical cancer research: an official journal of the American Association for Cancer Research vol. 23,16 (2017): 4569-4577. doi:10.1158/1078-0432.CCR-17-0151.
Verardo teaches a method for diagnosing a tumor or a cancer by determining if a tissue sample is positive for a biomarker (see [0033]). Verardo teaches the calculation the number of biomarker staining viable tumor or cancer cells found in the tissue sample divided by the total number of staining and non-staining viable tumor or cancer cells, multiplied by 100 (see [0004]) (instant claim 14).
Verardo does not teach determining the expression of Melanoma Associated Antigen Gene-A4 (MAGE- A4) in a tissue sample nor does Verardo teach TIPS of about 70%, or greater, 75% or greater, 80% or greater, or about 90% or greater indicating a positive diagnostic status of the tissue sample.
Williams teaches a method of using IHC to measure MAGE-A4 expression in a tissue sample to diagnose a subject with cancer (see claim 1 of ‘674, see [0001] – [0002], see [0023] – [0024]) (instant claim 14).
Williams does not teach TIPS of about 70%, or greater, 75% or greater, 80% or greater, or about 90% or greater indicating a positive diagnostic status of the tissue sample.
Cooper teaches the TIPS score being positive at 75% or more (see figure 3, see page 4575 “Impact was the highest for samples with a PD-L1 tumor proportion score >80% with 86.2% and 95.4% concordant assessments before and after training.”) (instant claims 6-7 and 14).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the method of assessing biomarker expression in a tumor or cancer taught by Verardo with the method of measuring MAGE-A4 expression in tissue and treating cancer with anti-MAGE-A4 antibodies taught by Williams, with the method of using TIPS to assess and diagnose non-small cell lung cancer taught by Cooper. Williams provides motivation for substituting the biomarker of Verardo with the MAGE-A4 biomarker of Williams by teaching that MAGE-A4 is a tumor-associated antigen belonging to the MAGE family of germline encoded cancer antigen and is the ideal target for therapeutic intervention and a high level of expression of MAGE-A4 has been reported in tumors (see [0002]). Cooper provides motivation by teaching that a TIPS score of 80% is a gold standard assessment score (see page 4574). The artisan would have reasonable expectation of success based on the cumulative disclosures of these prior art references.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MCKENZIE A DUNN whose telephone number is (571)270-0490. The examiner can normally be reached Monday-Tuesday 730 am -530pm, Wednesday-Friday 730 am-430 pm.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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