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 .
Response to Amendment
Applicant’s amendment and remark filed on 07/06/26 have been entered. Claims 26, 28, 30, 33, 37, 39, and 42-46 are cancelled. New claims 49-55 are added. Claims 25, 27, 29, 31-32, 34-36, 38, 40, 41, and 47-55 are pending and examined herein. Applicant’s amendment and remark have overcome each and every objection set forth in Office Action mailed on 03/16/26.
Status of Rejection and Objection
The rejection of claims 26, 28, 30, 33, 37, 39, and 42-46 are obviated by Applicant’s cancellation.
The rejection of claims 27 and 47 under 101 is withdrawn in view of Applicant’s amendment and remark.
The rejection of claims 25, 29, 31, 32, 34-36,38,48-50, and 52-55 under 101 is maintained.
The rejection of claims 25, 27, 29, 31-32,34-36, 38, 40, and 41 under 102 is withdrawn in view of Applicant’s amendment.
The amendment necessitates new ground of rejection.
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 25, 29, 31, 32, 34-36,38,48-50, and 52-55 are rejected under 35 U.S.C. 101 because the claimed invention is directed to mental process without significantly more.
Regarding claims 25, 40-41, and 48, the claims recite collecting data that is later reinterpreted/calculated, via a computing device, to a value, from which one of ordinary skill in the art will be able to diagnose a patient and prescribe treatment. This is insufficient to transform the abstract idea of a mathematical calculation and mental process of a comparison and a law of a nature (correlation of levels of FABP (heart-type fatty acid binding protein), N-terminal fragment of B-type natriuretic peptite (NT-proBNP), or D-Dimer (DDi) to diagnosis to large vessel occlusion (LVO)) into a patentable application.
The limitation recited in step d-e, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of mathematical calculation. The claim recites assigning a value to each obtained parameter and calculating a computed value based on the assigned values of the parameters. Though the claim recites assignment and computation of values are done via a computer, the claim limitation is recited so broadly and generically in a way that the algorithm/procedure could be performed purely by hand/mentally even though the claim procedures can be carried out on existing computers. “The Supreme Court recognized this in Benson, determining that a mathematical algorithm for converting binary coded decimal to pure binary within a computer’s shift register was an abstract idea. The Court concluded that the algorithm could be performed purely mentally even though the claimed procedures ‘can be carried out in existing computers long in use, no new machinery being necessary’” (MPEP 2106, III, C).
This limitation outputting diagnostic result indicative of likelihood of LVO, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of a mental process. The claim recites determining a diagnostic results based on assessment of the computed score/value. Making decision whether or not the difference of the comparison, under broadest reasonable interpretation, is a mental process that can be performed in the human mind. Nothing in the claim precludes the user from making decision based on computed score. Though the claim requires using a computer to output the diagnostic result. Using a computer as a tool to perform a mental process is still considered an abstract idea. . In “Berkheimer v. HP, Inc., 881 F.3d 1360, 125 USPQ2d 1649 (Fed. Cir. 2018), in which the patentee claimed methods for parsing and evaluating data using a computer processing system. The Federal Circuit determined that these claims were directed to mental processes of parsing and comparing data, because the steps were recited at a high level of generality and merely used computers as a tool to perform the processes. 881 F.3d at 1366, 125 USPQ2d at 1652-53” (MPEP 2106, III, C, 3). If a claim limitation, under its broadest reasonable interpretation, covers a mental process, then it falls within the mental process grouping. Accordingly, the claim recites an abstract idea (Step 2A, Prong 1).
These judicial exceptions are not integrated into a practical application, the additional limitations of the claims, i.e., collecting sample and determining the levels of biomarkers or collecting certain clinical data of the patients, do not add a meaningful limitation to the method as they are insignificant extra-solution activity. There is no integration of the diagnostic step much less a practical one since after the measurement and diagnosis is completed. Nothing is done with the information, there is no particular treatment step introduced in response to the diagnosis. Accordingly, this additional element does not integrate the mental process into a practical application because it does not impose any meaningful limits on practicing the abstract idea. (Step 2A, Prong 2).
Moreover, the claims do not include additional elements that are sufficient to significantly amount to any added inventive concept to the judicial exceptions as recognized by the court decisions listed in MPEP § 2106.05(d). The collection of samples and detection and measurement of FABP is a well understood and routine and conventional step that does not add an inventive concept to the judicial exceptions as cited above. See prior art cited below such as McConnell (Page 9, Sample Analysis).
None of the dependent claims recite limitations that integrate the judicial exception into a practical application.
Claims 38, 47, and 49-50 do not cure the deficiency of the parent claims. The claims require transferring the subject to a medical facility specialized in thrombectomy. Transferring someone to a medical facility does not necessarily mean a treatment is being administered. Someone can be referred to a medical facility and gets a “second opinion” from a specialist.
Claim 36 does not cure the deficiency of claim 25. Claim merely recites sample is a bio fluid.
Claims 29, 31, and 44 are only adding clinical parameters such as ages, gender, blood pressure into consideration to the study.
Claims 32, 34, and 48 do not cure the deficiency of the parent claims. The claims are only adding more biomarkers to test for in the original method of diagnosing LVO which are still not integrating the judicial exceptions into a practical application.
Claims 35 and 55 do not cure the deficiency of claim 25. The claim recites the timing when HFABP is determined, which is an insignificant extra-solution activity as discussed above.
Thus, the dependent claims do not have steps or elements that could integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d).
Claims 52 and 54 do not cure the deficiency of claims 25. The claims recite a highly generic assay method for measuring the biomarkers.
Claim 53 does not cure the deficiency of claim 25. The claims recite a threshold-based biomarker panel algorithm to the assigned values. Under the broadest reasonable interpretation, such algorithm evaluates multiple biomarkers against a specific numerical cut-off in order to classify disease states. As discussed above, the claim limitation is recited so broadly and generically in a way that the algorithm/procedure could be performed purely by hand/mentally by having an individual manually comparing the assigned values and the threshold.
For the reason(s) above, the claims are not patent-eligible.
Claims 27, 47, and 51 would cure the deficiency of the claims above as the claims require specific and particular treatment.
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 40-41 is/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.
Regarding claim 40, the claim recites a kit comprising instructions which, when executed by a computing device, cause the computing device to do the claimed task. In an apparatus claim, merely reciting an apparatus comprising instructions, which is inherently intangible/abstract, without explicitly being recited to be embodied in a physical structure is indefinite.
Claim 41 is also rejected for being dependent on claim 40.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that use the word “means” and are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: reagent means in claims 40-42.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The specification discloses the reagent means are “any antibody or reagent known to bind with high affinity to the target proteins” such as polyclonal sera, hybridoma supernatants or monoclonal antibodies, antibody fragments, Fv, Fab, Fab′y F(ab′)2, ScFv, diabodies, triabodies, tetrabodies and humanised antibodies (para. [0157]).
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 25, 27, 29, 31-32, 34-36, 38, 47, and 52-55 is/are rejected under 35 U.S.C. 103 as being unpatentable over McConnell (WO 2018228935 A1) as cited in the previous OA in view of Ain (Expert System for Stroke Classification Using Naïve Bayes Classifier and Certainty Factor as Diagnosis Supporting Device, 2020) and Sato (D-dimer level and outcome of minor ischemic stroke with large vessel occlusion, 2020)..
Regarding claim 25and 36, McConnell discloses a method for treating large vessel occlusion (LVO) in a subject, said method comprising:
obtaining an isolated sample from the subject, wherein the isolated sample is a bio fluid (EDTA plasma samples of blood obtained from the patients of the study group; Page 9, Sample Analysis);
measuring, in the isolated sample, a level of a heart-type fatty acid binding protein (HFABP) and a level of at least one of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) or D-Dimer (DDi) in the isolated sample (The following proteins were tested against EDTA plasma samples of blood obtained from the patients of the study group: h-FABP, D-dimer…Page 9, Sample Analysis); and
determining for the subject one or more clinical parameters selected from the group consisting of blood pressure, age, and a score for systematic assessment of stroke-related neurologic deficits (Stroke severity was measured at the time of admission with the National Institute of Health Stroke Scale (NIHSS). Functional outcome was measured with the modified Rankin scale (mRS) on day 7 and acute stroke patients were categorised into three severity groups (mild, moderate and severe) according to their mRS-score: mild (mRS-score:0-2), moderate (mRS-score:3-4) and severe (mRS-score:5-6). Patient Group, Page 9).
However, McConnell alone does not disclose step d-f. McConell also does not disclose the method of diagnosing the likelihood of LVO based on the computed value. Regarding step d, McConnel discloses the method can be further improved by incorporating a classification algorithm such as Naïve Bayes, which calculates the posterior probability-the chance (or a score) that a data point belongs to a specific class given its feature (The skilled person will be aware of numerous suitable methods for developing statistical algorithms…The present inventors have found that both multinominal logistic regression and Na'ive Bayes Classification achieve similar performance in the context of the present invention, suggesting the importance of the analytes (i.e. biomarkers) used in the methods of the invention, rather than the method used to generate the algorithmic model. However, in a preferred embodiment, the statistical algorithm includes Na'ive (N) Bayes classification. Page 5, para. 1).
In an analogous art, Ain discloses a stroke classification system using naïve bayes classifier (Abstract) comprising:
assigning, by a computing device, a value and/or score (Certainty Factor; Table 1, Number, Table 3) to each of the measured level of analytes (uric acid) and one or more clinical parameters (Age, weight history of heart disease, etc.; Table 1);
computing, by the computing device, the assigned values and/or scores to obtain a computed value (HMAP Stroke, HMAP Non-Stroke; Tables 4-5); and
generating, by the computing device a diagnostic output indicative of the lelihood of stroke based on the computed value (Diagnostic Decisions; Tables 4-5).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have utilized the algorithm disclosed by Ain in (2.1. Naïve Bayes Classifier Methods and 2.2 Certainty Factor Methods) to the method and experimental data points gathered by McConnell to derive the claimed invention with reasonable expectation of success. One would be motivated to do so as McConnell discloses the method can be enhanced with machine learning algorithm with Naïve Bayes as preferred model (Page 5, para. 1). Furthermore, Ain discloses the Naïve Bayes Classifier method gives a diagnosis of 96% (Page 7, para. 1).
The combination does not explicitly disclose the method is able to indicate the likelihood of LVO based on the computed value. Analogous art, Sato, discloses a method of diagnosing patients with LVO by examining the elevated level of D-dimer (A high D-dimer level on admission could help predict unfavorable outcomes in patients with a minor ischemic stroke with large vessel occlusion. Conclusions). The method considers additional clinical factors such as NIHSS score, mRS, prior history of stroke (2.1. Deviation cohort; Fig. 1) and age, sex, onset to door time, blood pressure (2.3. Clinical characteristics). Furthermore, the method involves identifying cut-off values of variables that could be used for discriminating between favorable and unfavorable outcomes (To identify the cut-off values of variables that could be used for discriminating between favorable and unfavorable outcomes, receiver operating characteristic (ROC) curves were constructed. 2.4. Statistical analysis, para. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have reconfigured the combined method of McConnell and Ain for the classification/diagnosis of LVO patients based on the data and procedure presented by Sato by recognizing difference in level of D-dimer in stroke patient can be further distinguish patients suffering LVO (The results in our study are consistent with these prior studies showing a correlation between a high D-dimer level and an unfavorable outcome and death following an acute ischemic stroke. However, the first distinctive point of our study is that we included only patients with an acute minor ischemic stroke with LVO whose intra- and extracranial vascular status was examined by MRA/MRI or CTA in the hyperacute phase. Second, in our study, the validity was successfully verified by applying the same model to the validation cohort from a single, highly specialized stroke center. Sato, 4. Discussions, para. 2). Since the current guideline recommend indiscriminately for anyone with NIHSS score 6 or more to be treated with thrombolysis or mechanical thrombectomy (Introduction, para. 2), one would be motivated to develop a more complex method considering more clinical factors in order to properly recommend patients to undergo specialized treatment (Therefore, identifying predictors of an unfavorable outcome in patients with a minor acute ischemic stroke with LVO based on available information in acute settings (e.g., demographics, past medical history, risk factors, vascular imaging findings, and laboratory data) is useful for clinicians who make therapeutic decisions. Introduction, para. 2, Sato; Fig. 1).
Regarding claims 27 and 47, McConnell discloses the claimed invention as discussed above in claim 25. McConnell discloses the reperfusion therapy is thrombectomy in combination with a previous administration of a thrombolytic drug (If as a result of carrying out the method of the invention it is determined that the patient has not suffered, or is not suffering, an IS or HS, further investigations can be made and blood thinners such as warfarin and aspirin may be prescribed and administered if necessary; page 8, para. 2).
Regarding claims 29 and31, Modified McConnell discloses the claimed invention as discussed above in claim 25. McConnell discloses the method further comprises determining one or more clinical parameters of the subject, wherein the clinical parameters of the subject are selected from gender, age (If two or more biomarkers are to be used in the diagnostic method a suitable mathematical model, such as logistic regression equation, can be derived. The logistic regression equation might include other variables such as age and gender of patient. Page 6, para. 1), glycemia (Traumatic brain injury, hypoglycaemia, hyperglycaemia…were stroke mimic events encountered in this study. Page 3, Detailed Description of the Invention), time from onset of symptoms (Blood samples (serum and EDTA plasma) were taken at the time of admission and at 24, 48, 72, 96 hours and 7 days post admission...The mean time from the onset of stroke-symptoms to hospital admission was 3.2 hours. Page 9, Patient Group), and systemic assessment tools of stroke-related neurologic deficits, wherein the score from systematic assessment tools of stroke-related neurologic deficits is selected from National Institutes of Health Stroke Scale (NIHSS) score (Stroke severity was measured at the time of admission with the National Institute of Health Stroke Scale (NIHSS). Page 9, Patient Group). The modification would have utilized the algorithm by Ain to obtain the computed value.
Regarding claim 32, Modified McConnell discloses the claimed invention as discussed above in claim 25. McConnell discloses the method further comprises determining the level of d-dimer and GFAP in the isolated sample of the subject (The following proteins were tested against EDTA plasma samples of blood obtained from the patients of the study group: h-FABP, D-dimer, GFAP…Page 9, Sample Analysis). The modification would have utilized the algorithm by Ain assigning a score to the GFAP level to obtain the computed value.
Regarding claim 34, Modified McConnell discloses the claimed invention as discussed above in claim 25. McConnell, after incorporation with Ain, discloses the measured levels and clinical parameters used to obtain the computed value comprise a combination selected from the group consisting of:
HFABP (Page 9, Sample Analysis), DDi (Page 9, Sample Analysis), NIHSS (Patient Group, Page 9), and age (Page 6, para. 1).
McConnell does not explicitly disclose DBP can be used as a clinical parameter. However, McConnell discloses high blood pressure is a contributing factor to be stroke cases (High blood pressure is estimated to be a contributing factor in 12.7 million of these 15 million stroke cases. Improvements to Stroke Diagnosis Background to the Invention, para. 1, page 1). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporated blood pressure parameter such as DBP as a clinical parameter based on the disclosure of McConell as McConnell discloses the blood pressure as a contributing factor in 13 millions out of 15 millions stroke cases.
Sato discloses clinical factors such as systolic blood pressure, diastolic blood pressure, blood glucose, age as additional clinical characteristics for consideration (2.3. Clinical characteristics; 3. Results; Table 1-3) as additional risk factors and (Comparing the patients' characteristics between the two cohorts, age, proportion of basilar artery occlusion, and levels of D-dimer and brain natriuretic peptide were significantly higher in the derivation cohort in univariate analyses (p < .001, p = .021, p = .032, and p = .005, Table 3). The proportion of endovascular treatment in the derivation cohort was significantly lower than that in the validation cohort. (p = .001, Table 3). D-dimer was evaluated in 129 patients in derivation cohort and all patients in validation cohort. 3. Results, para. 7; Table 3).
As such it would have been obvious to one of ordinary skill in the art to have considered additional risk factor such as DBP to the combination in McConnell before as blood pressure, as highlighted by both Sato and McConell, is a major risk factor/predictor for symptoms resulted from stroke and LVO.
Regarding claim 35, Modified McConnell discloses the claimed invention as discussed above in claim 25. McConnell discloses the HFABP, DDi, and the at least one clinical parameter are measured within the first six first hours after a stroke onset (Only patients admitted to the emergency department within 6 hours from the onset of neurological symptoms were included in the study. The mean time from the onset of stroke-symptoms to hospital admission was 3.2 hours. In each patient the presence of arterial hypertension, diabetes mellitus, smoking history, dyslipidemia and ischaemic heart disease were recorded. Stroke severity was measured at the time of admission with the National Institute of Health Stroke Scale (NIHSS). Page 9, Patient Group).
Regarding claim 38, Modified McConnell discloses the claimed invention as discussed above in claim 25. Ain (after incorporation) discloses the method further comprises identifying shifting the subject diagnosed with LVO to a centre for thrombectomy (If as a result of carrying out the method of the invention it is determined that the patient has suffered, or is suffering, a HS then these patients would typically be sent to a surgical unit to repair the damaged blood vessels. Page 8, para. 2).
Regarding claim 52, Modified McConnell discloses the claimed invention as discussed above in claim 25. McConnell addresses the issues of specificity and sensitivity. McConell provides a specificity value of 95% and sensitivity of about 85% (Table 1).
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Regarding claim 53, Modified McConnell discloses the claimed invention as discussed above in claim 25. McConell discloses a threshold-based biomarker panel algorithm to the assigned values and/or scores (A further aspect of the invention is a method of diagnosing or differentiating stroke in a patient who has suffered or is suffering stroke-like symptoms comprising taking a sample from the patient and determining the sample concentration of one or more of h-FABP, D-dimer, sTNFRI and IL-6 in which the following concentrations ('cut-off' concentration) taken individually support the diagnosis of IS in the patient: h-FABP≥ about 4.70 ng/ml, D- dimer≥ about 200 ng/ml, sTNFRI≥ about 2.30 pg/ml, IL-6≥ about 5.90 pg/ml. These cut-offs are displayed in Table 2 and are based on the ROC curves derived using stroke mimics and stroke mimics + TIA populations as the control group. Page 7-8).
Regarding claim 54, Modified McConnell discloses the measuring is performed by immunoassay or point-of-care testing (Sample Analysis, para. 1, page 9).
Regarding claim 55, Modified McConnell discloses the claimed invention as discussed above in claim 25. Sato, after incorporation, discloses measuring and determining are performed within the first two hours after stroke onset for some patients (Table 1, average onset to door time for mRS score 3-6 is 98 min; Table 2, average onset to door time for Validation cohort is 120 min).
Claim(s) 40-41 is/are rejected under 35 U.S.C. 103 as being unpatentable over McConell in view of Ain, Sato, and Merck (Measurement of cardiovascular disease biomarkers in human clinical samples using magnetic bead-based MILLIPLEX map multiplex panels, March 2015) as cited in the previous Office Action.
Regarding claim 40-41, McConell in view of Ain and Sato discloses the claimed instructions (See rejection of claim 25 above). Furthermore, McConell discloses for measuring the biomarkers, the method involves a kit comprising monoclonal antibodies for detecting the levels of a H-FABP and DDi (When identifying the various biomarkers of the invention it will be apparent to the skilled person that as well as identifying the full-length protein, the identification of a fragment or several fragments of a protein is possible, provided this allows accurate identification of the protein. Similarly, although a preferred probe of the invention is a polyclonal or monoclonal antibody. Page 4).
McConell does not explicitly disclose the kit comprises reagent means capable of detecting NT-proBNP. Sato discloses brain natriuretic peptide level should also be monitored for stroke/LVO detection (2.3. Clinical characteristics; Comparing the patients' characteristics between the two cohorts, age, proportion of basilar artery occlusion, and levels of D-dimer and brain natriuretic peptide were significantly higher in the derivation cohort in univariate analyses… para. 7, 3. Discussions; Table 1-3).
In an analogous art, Merck discloses a magnetic bead-based multiplex panels comprising monoclonal/polyclonal antibodies coated bead (antibody-conjugated beads and biotinylated detection antibody, CVD biomarker analysis, page 4) for simultaneously detecting (Each panel simultaneously measured multiple CVD biomarkers, CVD biomarker analysis, page 4) the levels of a HFABP (FABP3 and FABP4, Panel 1, page 5), NT-proBNP (Panel 1, page 5), and D-dimer (panel 2, page 5). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date to have incorporated the kit of detection of biomarkers of HFABP, NT-proBNP, and D-dimer of Mercks the kit of Modified McConell to derive the claimed invention. As Sato discloses BNP also correlates with stroke and LVO diagnosis, as such one of ordinary skill in the art would have considered Merck’s kit and NT-proBNP for further analysis and diagnosis of stroke type and LVO.
Claim(s) 48-51 is/are rejected under 35 U.S.C. 103 as being unpatentable over McConnell, Ain, and Sato as discussed above in claim 25, and further in view of Ho (The Prognostic significance of heart-type fatty acid binding protein in patients with stable coronary heart disease, 2018) as cited in previous Office Action.
Regarding claim 48, Modified McConnell discloses the claimed invention as disclosed above in claim 25. McConnell discloses the method further comprises determining the level of d-dimer (The following proteins were tested against EDTA plasma samples of blood obtained from the patients of the study group: h-FABP, D-dimer, GFAP…Page 9, Sample Analysis). However, neither McConnell, Ain, nor Sato discloses a step of determining the level of N-terminal fragment of B-type natriuretic peptide (NT-proBNP).
In an analogous art, Ho discloses an investigation of prognosis significance of H-FABP in patients with coronary heart disease. Specifically, NT-proBNP and H-FABP were measured as biomarkers (Baseline clinical and biomarker data collection). Ho discloses the patients with high level of H-FABP also have high level of NT-proBNP (…patients with a high level of H-FABP had significantly higher blood glucose…and N-terminal pro-brain natriuretic peptide (NT-proBNP) than those with a low level of H-FABP (Table 2); Results, Patients, para. 2; Table 2, page 3). Furthermore, Ho discloses the patients in the study including nonfatal strokes (Results, Patients, para. 1, page 2), suggesting a correlation between cardiovascular disease and strokes.
Therefore, based on Ho’s disclosure, it would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporated the detection NT-proBNP in conjunction of H-FABP level method of Modified McConnell to derive the claimed invention. One of ordinary skill in the art would have a reasonable expectation of success for the combination as Ho discloses the general positive predictive correlation between both H-FABP and NT-proBNP (…additional H-FABP measurements improved the diagnostic specificity and positive predictive value of NT-proBNP tests. Discussion, para. 4) in patients suffering both cardiovascular failure and a stroke (Clinical follow-up). Furthermore, additional biomarkers detection improves diagnostic specificity (…additional H-FABP measurements improved the diagnostic specificity and positive predictive value of NT-proBNP tests. Discussions, para. 4).
Regarding claim 49-51, Modified McConnell discloses the claimed invention as discussed above in claim 25. McConnell, after incorporation with Ain and Sato, discloses identifying the subject as suffering from LVO based on the output and transferring the subject to a thrombectomy-capable center to administer a reperfusion therapy comprising mechanical thrombectomy to the subject (If as a result of carrying out the method of the invention it is determined that the patient has suffered, or is suffering, a HS then these patients would typically be sent to a surgical unit to repair the damaged blood vessels. Page 8, para. 2).
Response to Arguments
Applicant's arguments filed 07/06/26 have been fully considered but they are not persuasive.
Regarding applicant’s remark toward the 101 rejection, the claim is directed to the newly amended limitation. At least for claim 1, applicant amend the method claim to introduce a computer-implemented process for calculation and determination of patient’s likelihood of suffering LVO based on the biomarkers concentration and other clinical characteristics data collected (Page 7-9), applicant argues that the claim now recites a specific computer-implemented process, when taken as a whole, recites a diagnostic and treatment applications that integrate any alleged judicial exception into practical application and recite significantly more than the judicial exception (page 9, para. 3-4).
Examiner respectfully disagrees. MPEP 2106.04(a)(2)(C) states thata claim that requires a computer may still recite a mental process. The Court concluded that the algorithm could be performed purely mentally even though the claimed procedures “can be carried out in existing computers long in use, no new machinery being necessary.” 409 U.S at 67, 175 USPQ at 675. “In evaluating whether a claim that requires a computer recites a mental process, examiners should carefully consider the broadest reasonable interpretation of the claim in light of the specification. For instance, examiners should review the specification to determine if the claimed invention is described as a concept that is performed in the human mind and applicant is merely claiming that concept performed 1) on a generic computer, or 2) in a computer environment, or 3) is merely using a computer as a tool to perform the concept. In these situations, the claim is considered to recite a mental process.”
In this case, at least for claim 25, it is determined that the computer-implemented steps recited are recited in a way that it does not preclude one from assigning and computing the values/scores by hand or mentally. “The Supreme Court recognized this in Benson, determining that a mathematical algorithm for converting binary coded decimal to pure binary within a computer’s shift register was an abstract idea. The Court concluded that the algorithm could be performed purely mentally even though the claimed procedures ‘can be carried out in existing computers long in use, no new machinery being necessary”
Regarding the limitation of diagnostic output for indication of likeliness of LVO, the step is, at best, using a computer as a tool to perform a mental process according MPEP 2106.04(a)(2)(C)(3). Though the claim requires using a computer to output the diagnostic result. Using a computer as a tool to perform a mental process is still considered an abstract idea. . In “Berkheimer v. HP, Inc., 881 F.3d 1360, 125 USPQ2d 1649 (Fed. Cir. 2018), in which the patentee claimed methods for parsing and evaluating data using a computer processing system. The Federal Circuit determined that these claims were directed to mental processes of parsing and comparing data, because the steps were recited at a high level of generality and merely used computers as a tool to perform the processes. 881 F.3d at 1366, 125 USPQ2d at 1652-53” (MPEP 2106, III, C, 3).
These judicial exceptions are not integrated into a practical application. There is no integration of the diagnostic step much less a practical one since after the measurement and diagnosis is completed. Nothing is done with the information, there is no particular treatment step introduced in response to the diagnosis.
MPEP 2106.04(d)(2) states “A claim reciting a judicial exception is not directed to the judicial exception if it also recites additional element(s) demonstrating that the claim as a whole integrates the exception into a practical application. One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition.” Simply stating a diagnosis step without a particular treatment is not sufficient to properly demonstrating that the claim as a whole integrates the exception into a practical judicial exception.
Examiner notes that incorporating claim 27 and 47 would have cured the deficiency and overcome the 101 rejection as these claims require an actual particular treatment (mechanical thrombectomy or thrombolytic drug. Note that simply reciting transferring the patient to a thrombectomy-capable center without explicit recitation of a administration of treatment is not sufficient as a patient can be simply referred to get a “second opinion” from a specialist for example.
For the reasons above, other than claims 27 and 47, the 101 rejection is maintained.
Applicant’s arguments with respect to claim(s) 25, 27, 29, 31-32, 34-36, 38, 40, 41 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. The rejection is specifically directed to the newly added limitation of steps d-f (for the method claims) and instructions encompassing the process steps d-f in a kit. Applicant argues that the reference does not sufficiently address LVO, which is more specific condition of a subtype of ischemic stroke (Page 10-11). Examiner believes that the newly cited reference, Sato (incorporated in the rejection of claim 25) would have addressed the new limitation as Sato discloses elevated D-dimer levels may be used for differentiating LVO patients from a ischemic stroke patient.
Conclusion
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.
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/M.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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