DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 24-26, 28-33, 35-40 and 42-52 are pending.
Claims 46-49, drawn to a non-elected invention is not examined on the merits.
Claims 27, 34 and 41 have been cancelled.
Claims 24, 31, 35 and 38 have been amended.
Claims 50-52 have been added.
Claims 24-26, 28-33, 35-40, 42-45 and 50-52 are examined on the merits.
Withdrawn Objections
Specification
3. The title of the invention is now descriptive, see Amendments to the Specification, page 2, 2nd paragraph.
4. The disclosure is no longer objected to because the phrase “membrane-bound actin” is consistently cited throughout the amended Specification, see Amendments to the Specification, page 2, 3rd paragraph.
Claim Objections
5. Claims 28, 35 and 43 are no longer objected to because the phrase “membrane-bound actin” is consistently cited in the amended claims, see Amendment to the Claims submitted December 31, 2025.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 112
6. The rejection of claim 41 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of the cancellation of the claim, see Amendment to the Claims submitted December 31, 2025, page 6.
Claim Rejections - 35 USC § 102
7. The rejection of claim(s) 24, 25, 28-30, 38, 39 and 43-45 under 35 U.S.C. 102(a)(1) as being anticipated by Habeeb et al., (Electronic Journal of General Medicine 17(2): 1-4, published 15 February 2020) is withdrawn in light of the amendment to claims 24 and 38, see Amendment to the Claims submitted December 31, 2025, pages 3 and 5; and corresponding arguments in Remarks, page 9, last two paragraphs submitted December 31, 2025.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 101
8. 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.
9. The claimed invention (claims 24-26, 28-33, 35-40, 42-45 and new claims 50-52) continues to be directed to a judicial exception and/or natural phenomenon without significantly more. Claims 27, 34 and 41 have been cancelled.
Applicant has amended claim 24 and added claims 50-52 including “…non-limiting examples of…therapeutics”, see Amendments to the Claims; and Remarks (page 9), both submitted December 31, 2025. Accordingly, Applicant avers the claims “are not directed to a judicial exception and/or natural phenomenon without significantly more”, see Remarks, page 9, 4th paragraph (para.).
Applicant’s amended claims, new claims, as well as arguments have been carefully considered. They fail to persuade.
Applicant’s claims recite conditional language, wherein if the level of membrane-bound actin is equal or higher than the reference level and if it is determined the subject is likely to have or will develop metastasis, a therapeutic is administered. Claim 24 cites a broad therapeutic.
And while Applicant has amended independent claims 24, 31 and 38 to include a therapeutic, thereby attempting to integrate the judicial exception into a practical application the rejection is maintained and made. Presence of the conditional language and the non-limiting therapeutic does not facilitate obviating the instant rejection.
Applicant’s claims are conditional claims, that is, if a condition in a method claim is not met, the conditional steps recited in the claims are not required to be performed, the administration step of the broad therapeutic is regarded as a recommendation. As such, there is no integration of the judicial exception into a practical application.
Moreover, the conditional claims also leave room for the implication, when test levels of membrane-bound actin are below the reference level there is no action, no administration step. There is no clear path recited, which the skilled artisan should execute “if” there are lower levels of membrane-bound actin detected or when membrane-bound actin is absent, as compared to the reference level. The decisions to render treatment are conditional and do not present how the clinician should proceed. Hence, the rejection is maintained for these reasons and of record.
Applicant should review MPEP 2111.04(II) for guidance regarding contingent and conditional claim limitations.
The claim(s) recite(s) methods of diagnosing metastatic cancer, determining the likelihood the cancer has metastasized, as well as prognosing the diagnosed cancer patient implementing measuring the level of membrane-bound actin, comparing the said level with the level of membrane-bound actin in a reference sample and determining potential outcomes including mortality. Moreover, if it is determined the likelihood of metastatic cancer will develop or has developed, a therapeutic is administered.
The presence or higher level of the membrane-bound actin in the test sample from the subject as compared to the level of the membrane-bound actin measured in the reference sample is indicative of the subject Is likely to have a metastatic cancer, developed metastasis, has a poor prognosis and/or reduced chance of survival.
Furthermore, claims 24, 31 and 38 all contain “if” language. This conditional language, does not note any consequence if the level of membrane-bound actin in the test sample is lower than the level of the membrane-bound actin found in the reference sample.
This judicial exception is not integrated into a practical application because gathering information and observing levels of candidate cancer biomarkers in a biological sample from a subject required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because it does not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The analysis as set forth in the 2019 Guidance is as follows:
Step 1: Yes, claims are drawn to a method which is one of the four statutory categories, a process.
Step 2A, prong 1: Yes, the claims recite/describe/set forth a judicial exception. The claims describe the relationship between the level of a membrane-bound actin in a subject’s biological sample or test sample. The presence of the membrane-bound actin, as well as a higher level of membrane-actin measured in a test sample as compared to the level of membrane-bound actin expressed by the reference is indicative of the subject is likely to develop or have metastasis, and will have a poor prognosis and/or reduced chance of survival.
Step 2A, prong 2: No, the judicial exception is not integrated into a practical application. The claims do not rely on or use the exception here. Once the level of the membrane-bound actin is detected at a different level than the reference level of membrane-bound actin by conventional and art known means, there are no additional elements or combination of additional elements to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The amended claims state the likelihood of developing metastasis or has developed metastases and/or given a poor prognosis, any cancer therapeutic is to be administered.
Step 2B: There is no inventive concept present in the clams. The steps of analyzing, measuring and detecting the level of membrane-bound actin in a biological sample at a different level than the reference level for the said protein is established by well understood, routine conventional methods, and in addition they are pre-solution activity, i.e. data gathering necessary to perform the correlation. The following claims and steps inform one of ordinary skilled in the art the comparison and the different levels of candidate cancer biomarkers with subsequent observation of expression or higher expression identifies the subject as having a metastatic cancer, increased likelihood of developing metastasis and/or likelihood the subject has reduced chances of survival. The subsequent administration of an anti-cancer treatment is also well understood and routine in art. The claims do not recite additional elements that amount to significantly more than the judicial exception. Accordingly, these claims are not be eligible under step 2A or step 2B.
Claims 24-26, 28-34, 35-40, 42-45 and 50-52 are drawn to a non-statutory method having a "natural principle" as a limiting element or step without reciting additional elements/steps that integrate the natural principle into the claimed invention such that the natural principle is practically applied, and are sufficient to ensure that the claim amounts to significantly more than the natural principle itself. In the instant case, the "natural principle" is: detecting presence of membrane-bound actin or increased level of presence of membrane-bounds in a biological sample from a subject is indicative the subject has a metastatic cancer, the likelihood the cancer will metastasize, and/or has a poor prognosis with a reduced chance of survival. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because assaying for candidate cancer biomarkers does not add significantly more and is not an inventive concept. Because methods for making such determinations were well known in the art, these steps simply tell researchers to engage in well-understood, routine, conventional activity previously engaged in by scientists in the field. Such activities are normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such law. Detection of candidate cancer biomarkers to evaluate patients with suspected metastatic cancer and further prognostication has been observed by applicant but not engineered by applicant. The claims do not add significantly more to the natural phenomenon because the claims do not require a novel reagent, apparatus or incorporate a novel treatment based on the correlation.
A claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. Recited elements such as “measuring”, “comparing” and “determining”, based on the natural principle impose no meaningful limit on the performance of the claimed invention. As set forth the claims do not impose meaningful limits on the performance of the claimed invention. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas). Further, the active method steps are conventional and routine in the art for the reasons stated above and the claims do not amount to significantly more than the recited natural principle. The claims do not "practically apply" the natural principle; rather, the claims "simply inform" the natural principle to one performing routine active method steps and do not amount to significantly more than the natural principle itself. Thus, the technology used by the instant claims is well-known in the art and does not contribute significantly more to the judicial exception. See the 2019 Revised Patent Subject Matter Eligibility Guidance and Federal Register https://www.federalregister.gov/documents/2019/10/18/2019-22782/october-2019-patent-eligibility-guidance-update; and FDsys.gov.
Claim Rejections - 35 USC § 102
10. 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.
11. The rejection of claim(s) 24-26, 28-33, 35-40, 42-45 and new claims 50-52 under 35 U.S.C. 102(a)(1) as being anticipated by Schettini et al., US 2015/0301058 A1 (published October 22, 2015) is maintained and made. Claims 27, 34 and 41 have been cancelled.
Applicant asserts “[w]hile Schettini discloses biomarkers which can be used to indicate metastasis and poor prognosis, Schettini does not disclose actin among these biomarkers. Where Schettini teaches in Table 5 (see discussion below) that actin is a common vesicle marker, a breast cancer marker, a ductal carcinoma in situ marker, a lung cancer marker, a head and neck cancer vesicle, a VEGF protein and a tumor marker, but does not include actin among the markers explicitly indicating metastasis and poor prognosis, it is clear that Schettini has not contemplated actin for this
purpose. The teachings of Schettini are therefore that biomarkers not including actin would need to be used if searching for likelihood of metastasis, and a person of skill in the art would therefore have no reasonable expectation of success of defining metastasis using actin based on these teachings.”, see Remarks submitted December 31, 2025, page 10, 5th paragraph (para.).
Applicant concludes arguments stating “[they] [believe] that the person of skill in the art would clearly understand that the paragraph [0433] statement is made in reference to the biomarkers specifically highlighted as relating to prognosis/metastasis…The present application therefore discloses a use of actin which is completely unexpected in view of the disclosures of Habeeb and Schettini. The present claims are therefore novel and inventive in view of the cited references.”, see page 11 of the Remarks, 2nd paragraph (para.).
Applicant’s arguments have been carefully considered, but fail to persuade.
While Applicant points out sections and pages, classifying “…what the different biomarkers might be used for”, “metastatic v. non-metastatic” and “biomarkers specifically associated with prognosis and metastatic cancers”, see para. bridging pages 10 and 11; and 1st full para. on page 11. The disclosure of additional terms and classification does not preclude the disclosure of actin beta on page 84, 1st line of protein.
Applicant’s arguments reading on classifications and descriptions are also of note under the phrase, illustrative class in Table 5. This phrase is a descriptor, however not limiting of how and what the illustrative biomarker is in its entirety.
Notwithstanding, Applicant has not pointed out, nor presented any scientific evidence that would dissuade. Applicant’s assertions or opinion regarding the prior art reference constitutes mere argument of counsel and cannot take the place of evidence lacking in the record, see Meitzner v. Mindick, 549 F.2d 775, 782, 193 USPQ 17, 22 (CCPA 1977). The unsupported assertions do not establish fact(s).
The actin beta is one and the same as Applicant’s membrane-bound actin, absent evidence to the contrary. Applicant has submitted the disclosed actin is a breast cancer marker, see Remarks, page 10, 5th paragraph and last complete sentence. Products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses
and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990), see MPEP 2112.01.
Furthermore, Schettini “… provides a method of treating or ameliorating a disease associated with a neoplastic growth, comprising administering the pharmaceutical composition to a patient in need thereof. In some embodiments, the pharmaceutical composition and method of use are used to treat a cancer patient” including breast cancer, see page 9, section 0055.; and Therapeutics segment on page 160. A HER2 blocking antibody, Herceptin® (trastuzumab), chemotherapy and neo-adjuvant therapy are disclosed as therapeutics for administration, see page 123, Table 7, condition: breast cancer; pages 124 and 125; page 127, section 0669; and page 134, section 0679. Hence the rejection is maintained and made.
Schettini discloses methods of identifying and assaying membrane bound antigens that can be shed from vesicles, as well as polypeptides biomarkers to characterize a cancer phenotype, state of the cancer, and poor or good disease outcome, see page 14, section 0092; page 21, section 0130; page 22, section 0137; page 43, section 0279; page 60, 0420; page 61, section 0432; page 89, section 0433; page 100, section 0500; and page 206, section 1501. One biomarker that can be used characterize a disease including breast cancer is beta actin, see page 61, section 0432; and Table 5, page 84, Protein segment, line 1. These biomarkers are identified and assayed from test samples, including blood, saliva and tissue biopsy, see page 2, segment 0019; page 19, section 0125; and page 21, section 0130.
The biomarkers assayed from a test sample not only characterize cancers, but “…the state of the cancer (e.g., metastatic v. non-metastatic)”, see page 89, section 0433; and page 124, sections 0664 and 0665. Once the biomarkers and biosignatures are identified, cancer is categorized cancer treatment may commence, see page 124, sections 0664-0670; and Table 8 spanning pages 124-126. Treatments include radiation, chemotherapy, combination therapies and surgery, see page 124, sections 0664-0670; and Table 8 spanning pages 124-126.
Comparison between the subject’s test sample can be compared with a reference sample, wherein “…a reference value can be from the same subject from whom a sample is assessed, or the reference value can be from a representative population of samples (e.g., samples from normal subjects not exhibiting a symptom of disease). Therefore, a reference value can provide a threshold measurement which is compared to a subject sample's readout for a biosignature assayed in a given sample. Such reference values may be set according to data pooled from groups of sample corresponding to a particular cohort, including but not limited to…, normal versus diseased subjects, smoker v. non-smoker, subject receiving therapy versus untreated subject, different time points of treatment for a particular individual or group of subjects similarly diagnosed or treated or combinations thereof. Furthermore, by determining a biosignature at different timepoints of treatment for a particular individual, the individual's response to the treatment or progression of a disease or condition for which the individual is being treated for, can be monitored.”, see section 0292. “Reference values can also be established for disease recurrence monitoring (or exacerbation phase in MS),”, thereby prognosticating increased likelihood for reduced chance of survival, see sections 0292 and 0297.
“As disclosed herein, methods are disclosed for characterizing a phenotype for a subject by assessing one or more biomarkers, including vesicle biomarkers and/or circulating biomarkers…Characterizing a phenotype can include providing a theranosis for a subject, such as determining if a subject is predicted to respond to a treatment or is predicted to be non-responsive to a treatment. A subject that responds to a treatment can be termed a responder whereas a subject that does not respond can be termed a non-responder. A subject suffering from a condition can be considered to be a responder for a treatment based on, but not limited to, an improvement of one or more symptoms of the condition; a decrease in one or more side effects of an existing treatment; an increased improvement, or rate of improvement, in one or more symptoms as compared to a previous or other treatment; or prolonged survival as compared to without treatment or a previous or other treatment. For example, a subject suffering from a condition can be considered to be a responder to a treatment based on the beneficial or desired clinical results including, but are not limited to, alleviation or amelioration of one or more symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. Treatment also includes prolonging survival as compared to expected survival if not receiving treatment or if receiving a different treatment.”, see page 120, section 0649.
Schettini “… provides a method of treating or ameliorating a disease associated with a neoplastic growth, comprising administering the pharmaceutical composition to a patient in need thereof. In some embodiments, the pharmaceutical composition and method of use are used to treat a cancer patient” including breast cancer, see page 9, section 0055.; and Therapeutics segment on page 160. A HER2 blocking antibody, Herceptin® (trastuzumab), chemotherapy and neo-adjuvant therapy are disclosed as therapeutics for administration, see page 123, Table 7, condition: breast cancer; pages 124 and 125; page 127, section 0669; and page 134, section 0679.
Claim Rejections - 35 USC § 103
12. 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.
13. The rejection of claim(s) 24-26, 28-33, 35-40, 42-45 and new claims 50-52 under 35 U.S.C. 103 as being unpatentable over Habeeb et al., (Electronic Journal of General Medicine 17(2): 1-4, published 15 February 2020), and further in view of Schettini et al., US 2015/0301058 A1 (published October 22, 2015) is maintained and made. Claims 27, 34 and 41 have been cancelled.
Applicant asserts “[w]hile Schettini discloses biomarkers which can be used to indicate metastasis and poor prognosis, Schettini does not disclose actin among these biomarkers. Where Schettini teaches in Table 5 (see discussion below) that actin is a common vesicle marker, a breast cancer marker, a ductal carcinoma in situ marker, a lung cancer marker, a head and neck cancer vesicle, a VEGF protein and a tumor marker, but does not include actin among the markers explicitly indicating metastasis and poor prognosis, it is clear that Schettini has not contemplated actin for this
purpose. The teachings of Schettini are therefore that biomarkers not including actin would need to be used if searching for likelihood of metastasis, and a person of skill in the art would therefore have no reasonable expectation of success of defining metastasis using actin based on these teachings.”, see Remarks submitted December 31, 2025, page 10, 5th paragraph (para.).
Applicant concludes arguments stating “[they] [believe] that the person of skill in the art would clearly understand that the paragraph [0433] statement is made in reference to the biomarkers specifically highlighted as relating to prognosis/metastasis…The present application therefore discloses a use of actin which is completely unexpected in view of the disclosures of Habeeb and Schettini. The present claims are therefore novel and inventive in view of the cited references.”, see page 11 of the Remarks, 2nd paragraph (para.).
Applicant’s arguments have been carefully considered, but fail to persuade.
The rationale for Schettini not falling is cited in the pending 102 rejection in the preceding pages. Moreover, Schettini “… provides a method of treating or ameliorating a disease associated with a neoplastic growth, comprising administering the pharmaceutical composition to a patient in need thereof. In some embodiments, the pharmaceutical composition and method of use are used to treat a cancer patient” including breast cancer, see page 9, section 0055.; and Therapeutics segment on page 160. A HER2 blocking antibody, Herceptin® (trastuzumab), chemotherapy and neo-adjuvant therapy are disclosed as therapeutics for administration, see page 123, Table 7, condition: breast cancer; pages 124 and 125; page 127, section 0669; and page 134, section 0679.
As for Habeeb, as Applicant submits, it does discuss “…beta-actin and its relationship to breast cancer”, see Remarks page 10, 3rd paragraph. And while Applicant asserts there is no “…evidence of a link between actin and metastases”, the actin is one and the same. Accordingly, the “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”, see MPEP 2112.01 (II). Hence, the rejection is maintained and made for the reasons of record and herein.
Habeeb teaches beta-actin (ACTB) expression is deregulated, as well as upregulated in tumor cells and tissues, see page 3, column (col.) 2, 1st paragraph (para.). “In all cancer patients the DNA concentrations were significantly higher p<0.0001, than those of the control group.”, see Results on page 1.
The ACTB was sampled from circulating tumor DNA (ctDNA), see page 1, Methods segment within the Abstract. “Plasma samples were collected from 55 patients 40 patients with breast cancer, 5 patients each with other type[s] of cancer (ovarian cancer, colon cancer, stomach cancer) and 20 healthy controls. Real-time PCR of β-actin gene were investigated using two primer sets (400 and 100bp) to amplify different DNA fragment lengths.”, see page 1, Methods segment within the Abstract. “The nucleic acid in the blood can be seen as a positive test of carcinoma. ctDNA in patients with cancer may be caused by cancer cells detached from the mass of the tumor and necrosis or apoptosis.”, see page 3, para. bridging both columns.
“ACTB is strongly correlated with a multitude of cancers, however, and cumulating proof shows that ACTB is deregulated in melanoma, liver, kidney, gastric, colorectal, esophageal, lymphoma, prostate, pancreatic, lung, ovarian, breast, and leukemia. In most tumor cells and tissues, ACTB is usually discovered to be up-regulated. The aberrant polymerization and expression of ACTB and the resulting modifications to the cytoskeleton was shown to be consistent with metastasis and invasive cancer.”, see page 3, 2nd col., 1st para.
Habeeb does not teach the method wherein the sample is a tissue biopsy, blood sample or a saliva sample and the diagnosed cancer is metastatic and a therapeutic is administered. Habeeb does not implement a reference/control sample that is known to be metastatic Habeeb also does not teach the method wherein the subject is given a poor prognosis with an increased likelihood of developing a metastasis and/or a reduced chance of survival and administered treatment is adjuvant chemotherapy or Her2 blocking monoclonal antibody treatment.
However, Schettini teaches methods of identifying and assaying membrane bound antigens that can be shed from vesicles, as well as polypeptides biomarkers to characterize a cancer phenotype, state of the cancer, and poor or good disease outcome, see page 14, section 0092; page 21, section 0130; page 22, section 0137; page 43, section 0279; page 60, 0420; page 61, section 0432; page 89, section 0433; page 100, section 0500; and page 206, section 1501. One biomarker that can be used characterize a disease including breast cancer is beta actin, see page 61, section 0432; and Table 5, page 84, Protein segment, line 1. These biomarkers are identified and assayed from test samples, including blood, saliva and tissue biopsy, see page 2, segment 0019; page 19, section 0125; and page 21, section 0130.
The biomarkers assayed from a test sample not only characterize cancers, but “…the state of the cancer (e.g., metastatic v. non-metastatic)”, see page 89, section 0433; and page 124, sections 0664 and 0665. Once the biomarkers and biosignatures are identified, cancer is categorized cancer treatment may commence, see page 124, sections 0664-0670; and Table 8 spanning pages 124-126. Treatments include radiation, chemotherapy, combination therapies and surgery, see page 124, sections 0664-0670; and Table 8 spanning pages 124-126.
Comparison between the subject’s test sample can be compared with a reference sample, wherein “…a reference value can be from the same subject from whom a sample is assessed, or the reference value can be from a representative population of samples (e.g., samples from normal subjects not exhibiting a symptom of disease). Therefore, a reference value can provide a threshold measurement which is compared to a subject sample's readout for a biosignature assayed in a given sample. Such reference values may be set according to data pooled from groups of sample corresponding to a particular cohort, including but not limited to…, normal versus diseased subjects, smoker v. non-smoker, subject receiving therapy versus untreated subject, different time points of treatment for a particular individual or group of subjects similarly diagnosed or treated or combinations thereof. Furthermore, by determining a biosignature at different timepoints of treatment for a particular individual, the individual's response to the treatment or progression of a disease or condition for which the individual is being treated for, can be monitored.”, see section 0292. “Reference values can also be established for disease recurrence monitoring (or exacerbation phase in MS),”, thereby prognosticating increased likelihood for reduced chance of survival, see sections 0292 and 0297.
“As disclosed herein, methods are disclosed for characterizing a phenotype for a subject by assessing one or more biomarkers, including vesicle biomarkers and/or circulating biomarkers…Characterizing a phenotype can include providing a theranosis for a subject, such as determining if a subject is predicted to respond to a treatment or is predicted to be non-responsive to a treatment. A subject that responds to a treatment can be termed a responder whereas a subject that does not respond can be termed a non-responder. A subject suffering from a condition can be considered to be a responder for a treatment based on, but not limited to, an improvement of one or more symptoms of the condition; a decrease in one or more side effects of an existing treatment; an increased improvement, or rate of improvement, in one or more symptoms as compared to a previous or other treatment; or prolonged survival as compared to without treatment or a previous or other treatment. For example, a subject suffering from a condition can be considered to be a responder to a treatment based on the beneficial or desired clinical results including, but are not limited to, alleviation or amelioration of one or more symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. Treatment also includes prolonging survival as compared to expected survival if not receiving treatment or if receiving a different treatment.”, see page 120, section 0649.
And Schettini “… provides a method of treating or ameliorating a disease associated with a neoplastic growth, comprising administering the pharmaceutical composition to a patient in need thereof. In some embodiments, the pharmaceutical composition and method of use are used to treat a cancer patient” including breast cancer, see page 9, section 0055.; and Therapeutics segment on page 160. A HER2 blocking antibody, Herceptin® (trastuzumab), chemotherapy and neo-adjuvant therapy are taught as therapeutics for administration, see page 123, Table 7, condition: breast cancer; pages 124 and 125; page 127, section 0669; and page 134, section 0679.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further sample additional biological samples and dissimilar reference/control samples to measure, quantify, distinguish and differentiate candidate cancer biomarker(s) between the two sets of samples. This analysis allows the skilled artisan to arrive at a biosignature, thereby yield information regarding the status of the disease, diagnosing disease, prognosticating the likelihood the cancer will progress, recur and the patient’s options for clinical course of action, treatment with the HER2 blocking antibody, Herceptin® (trastuzumab), chemotherapy and neo-adjuvant therapy taught by Schettini, see page 123, Table 7, condition: breast cancer; pages 124 and 125; page 127, section 0669; and page 134, section 0679.
One of ordinary skill in the art would have been motivated to integrate, combine and implement the teachings of Habeeb and Schettini to sample different biological samples for the early genetic marker of breast cancer, ACTB to further evaluate with the additional assays of Schettini to confirm ACTB’s status as a marker for metastasis and determine/confirm if ACTB is indicative of stage, estimated rate of survival and commence targeted therapy as taught by Schettini. One of ordinary skill in the art would have been motivated to commence treatment known it would be beneficial, alleviating symptoms and/or prolong survival, see page 120, section 0649.
Conclusion
14. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
15. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached on 8AM-8PM, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
28 January 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643