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 .
DETAILED ACTION
Election/Restrictions
1. Applicant's election of Group I, claims 1, 3-15, 18, and 21-25, with traverse, filed June 15, 2026 is acknowledged and has been entered. Upon further consideration, claims 17 and 20 have been rejoined with Group I for prosecution on the merits. Claims 2, 16, and 19 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being claims drawn to a non-elected invention. Accordingly, claims 1-25 are pending. Claims 1, 3-15, 17, 18, and 20-25 are under examination.
2. Applicant traverses the restriction requirement on the grounds that there is no burden to search all the groups as set forth by the Examiner.
Applicant’s argument is not found persuasive because Applicant is referring to the requirement to demonstrate search burden that pertains to applications filed under 35 U.S.C. 111(a) (see MPEP 801). The present application was filed under 35 U.S.C. 371 and is therefore subject to different analysis for restriction, namely unity of invention (see also MPEP 823 and 1800). There is no corresponding requirement to demonstrate search burden in applications filed under 35 U.S.C. 371.
In summary, Applicant’s arguments do not address unity of invention, and it is maintained that unity is lacking for reasons of record.
Priority
3. Applicant’s claim for the benefit of a provisional application under 35 U.S.C. 111(a) and 37 C.F.R 1.53(b) is acknowledged. Based on the filing receipt, the effective filing date of this National Stage application, which is a 371 of PCT/US2022/076076 filed 09/07/2022, is September 7, 2021 which is the filing date of Provisional Application 63/241,518 from which the benefit of priority is claimed.
Drawings
4. The drawings are objected to under 37 CFR 1.83(a) because they fail to show Figure 10B as described in the specification. Figure 10B appears to be missing in the Drawings.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Information Disclosure Statement
5. The listing of references in page 102 of the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
6. Claims 13-15, 17, and 23-25 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.
Claim 13 is indefinite in reciting, “SMOC-2”. Acronyms or abbreviations should be fully defined and recited at least one time in a given set of claims.
Claim 13 is indefinite in lacking clear antecedent basis in reciting “the two or more ATTR Biomarkers do not comprise SMOC-2” because claim 1 from which claim 13 depends does not appear to comprise SMOC-2 as an ATTR Biomarker.
Claim 14 is indefinite in reciting, “DCN”. Acronyms or abbreviations should be fully defined and recited at least one time in a given set of claims.
Claim 14 is indefinite in lacking clear antecedent basis in reciting “the two or more ATTR Biomarkers do not comprise DCN” because claim 1 from which claim 13 depends does not recite DCN as an ATTR Biomarker.
Claim 15 is indefinite in lacking clear antecedent basis in reciting “the two or more ATTR Biomarkers do not comprise SMOC-2 or DCN” because claim 1 from which claim 13 depends does not recite SMOC-2 or DCN as ATTR Biomarkers.
Claim 17 is vague and indefinite in reciting “A composition comprising: a) one or more ATTR Biomarkers, wherein the … ATTR Biomarkers comprise: (i) TnI, (ii) PKM1. (iii) PKM2 … (vii) NfL” because it is unclear how these proteins being biomarkers of transthyretin amyloidosis disease which can be detected in blood sample of a subject, are part of a composition, as claimed.
Claim 23 is indefinite in reciting “one or more control samples” because “control” is a subjective term lacking a comparative basis for defining its metes and bounds. See also claim 24.
Claim 25 recites “Use of a kit … in an in vitro diagnostic assay to diagnose TTR-CM in a subject;” however, claim 25 is indefinite because it fails to clearly define what method steps encompass this claimed use.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
7. Claims 3, 4, and 6-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, and 15 of copending Application No. 19/159,138 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions recite a method comprising detecting a level of two or more transthyretin amyloidosis (ATTR) biomarkers in a blood sample of a human subject. The two or more ATTR biomarkers comprise neurofilament light chain (NfL). The ATTR biomarkers are used to obtain an ATTR Biomarker profile of the subject which is used to compute an ATTR Biomarker score for the subject by computing an ATTR Biomarker score via application of an algorithm to the ATTR Biomarker profile.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
8. Claims 1, 3-15, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 76-83, 87-96, 99-113 of copending Application No. 19/159,012 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions recite a method comprising detecting a level of two or more ATTR biomarkers in a blood sample of a human subject. The two or more ATTR biomarkers comprise: (i) troponin I (TnI), (ii) pyruvate kinase muscle isoform 1 (PKM1), (iii) pyruvate kinase muscle isoform 2 (PKM2), (iv) N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), (v) retinol binding protein 4 (RBP4), (vi) tissue inhibitor of metalloproteinase 2 (TIMP2), (vii) neurofilament light chain (NfL), or (viii) a combination thereof; wherein the two or more ATTR biomarkers are used to obtain an ATTR Biomarker profile of the subject which is further used to compute an ATTR Biomarker score for the subject; and wherein computing the ATTR Biomarker score comprises applying an algorithm to the ATTR Biomarker profile derived from any one of decision tree methodology, a neural boosted methodology, a bootstrap forest methodology, a boosted tree methodology, or a support vector machines methodology. The ATTR Biomarker profile is received by a processor of a computing device which computes the ATTR Biomarker score which is further used to determine if the subject from which the sample was obtained is at risk of or suffering from transthyretin amyloid cardiomyopathy (TTR-CM) and used to diagnose TTR-CM.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
9. Claims 1, 3-15, and 25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Based upon an analysis with respect to each of these claims as a whole, these claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The claims recite a correlation between blood protein biomarkers troponin I (TnI), N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), pyruvate kinase muscle form 1 (PKM1), pyruvate kinase muscle form 2 (PKM2), retinol binding protein 4 (RBP4), tissue inhibitor metalloproteinase 2 (TIMP2), and neurofilament light chain (NfL) and transthyretin cardiac amyloidosis (ATTR) or the presence of transthyretin amyloid cardiomyopathy (TTR-CM) in a subject. This judicial exception is not integrated into a practical application because the claimed invention is limited to a correlation being categorized as a law of nature/natural phenomenon or existence in nature apart from any human action without significantly more. The claims do not include additional elements that are sufficient to amount to significantly more because the judicial exception is not integrated into a significant practical application in a manner that imposes a meaningful limit on the judicial exception. This new consideration is based on case law including Vanda, for evaluation of particular treatment or prophylaxis limitations.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A Prong One
The claims recite detecting the level of ATTR biomarkers in blood sample of a subject; the biomarkers being TnI, NT-proBNP, PKM1, PKM2, RBP4, TIMP2, and NfL to provide an ATTR biomarker profile, then applying an algorithm to the ATTR biomarker profile to compute an ATTR biomarker score that provides indication of TTR-CM.
The claimed steps of detecting the level of ATTR biomarkers in blood sample from a subject to create an ATTR profile that provides an ATTR biomarker score; thereby, providing indication of TTR-CM read on mental processes, such as a physician obtaining data result from a patient, analyzing the result, and forming an opinion regarding the subject’s likely diagnosis or prognosis of the disease. See the 2019 Revised Patent Subject Matter Eligibility Guidance (“2019 PEG”), issued on 1/7/2019 and available at https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf. Such steps of performing statistical analysis of different biomarker levels read on mental processes insofar as such data analysis could take place wholly in the human mind, or by a human using pen and paper. Similar mental processes have been held by the courts to be abstract ideas, e.g., collecting and comparing known information in Classen, or comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC. Such concepts as assessing between normal and abnormal results by performing clinical tests for biomarkers, determining abnormal elevated or decreased biomarker levels, and analyzing the results have also been characterized by the courts as abstract ideas. Additionally, the correlation between the ATTR biomarker levels and the presence of TTR-CM is also categorized as a law of nature/natural phenomenon. This is a judicial exception as the correlation exists in nature apart from any human action (July 2015 Update, Quick Reference Sheet; see also Univ. of Utah Research Found. v. Ambry Genetics Corp., 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)).
The claimed step of applying an algorithm to the ATTR biomarker profile to compute an ATTR biomarker score also recite mathematical processes encompassed in “mathematical concepts” in order to obtain a number or a variable or index or in this case, a score that is deemed to be representative of indication of the presence of TTR-CM disease. A mathematical calculation is a mathematical operation (such as multiplication or mathematical formula) or an act of calculating using mathematical algorithms to determine a mathematical data such as in this case, a score calculated from the ATTR biomarker profile that provides correlation to TTR-CM disease.
Such steps of computing in order to determine an ATTR biomarker score using mathematical algorithms have also been held by the courts to be abstract ideas or mental steps (i.e. performing a resampled statistical analysis to generate a resampled distribution, SAP Am., Inc. v. InvestPic, LLC,20; calculating a number representing an alarm limit value using the mathematical formula ‘‘B1=B0 (1.0–F) + PVL(F),’’ Parker v. Flook;21 and using a formula to convert geospatial coordinates into natural numbers, Burnett v. Panasonic Corp.22). As set forth supra, the judicial exception recited is not integrated into a practical application because steps corresponding to mental activity, which could be performed by programming mathematical algorithms, are insufficient to constitute a practical application.
Step 2A Prong Two
“Integration into a practical application” requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception; evaluating whether any additional element is recited beyond the judicial exception; and determining whether the additional element(s) integrate the exception into a practical application of the exception. This new consideration is based on case law including Vanda, for evaluation of particular treatment or prophylaxis limitations.
With respect to claims 1, 3, 6, 7 and 8, this judicial exception is not integrated into a practical application because statistical analysis steps corresponding to mental activity, which could be performed in a practitioner’s head, are insufficient to constitute a practical application. In this case, indicating/ diagnosing / prognosing the presence TTR-CM, without significantly more, is a judicial exception and not a practical application thereof.
There are no subsequent steps in claims 1, 3, 6, 7 and 8 recited that would be performed depending on the results of the assay. As in Mayo, there is no requirement that a physician act on the results of the methods. Rather, the claims merely inform a relevant audience about the judicial exception, at most amounting to a suggestion that the health provider should take those laws into account when treating the patient. There are no subsequent steps recited that would practically apply the method depending on the results of the method, i.e. process steps that integrate the natural principle into the method and assure that it is applied in some practical manner.
It is also noted that the claims do not clearly recite or require any physical or laboratory steps to be performed, such as performing immunological assays that measure the ATTR biomarkers. Steps of “detecting levels of the ATTR biomarkers” when given their broadest reasonable interpretation, could read on reading numbers off of a chart, which would also constitute mental activity.
Although claims 1, 3, and 25 do invoke an active step of “detecting” or “using an in vitro assay,” this is not a practical application of the judicial exception because such steps are merely data gathering steps. The detecting of level steps are recited at a high level of generality and are not tied, for example, to a particular machine or apparatus. Accordingly, even if the claims are interpreted as requiring a wet assay step to detect or measure the biomarkers of claims 1, 3 and 25, such steps are insufficient because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015).
As above, there are no subsequent steps recited in claims 1, 3, and 25 that would practically apply the methods depending on the results of the method, i.e. process steps that integrate the natural principle into the method and assure that it is applied in some practical manner.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Step 2B
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
In addition to the judicial exceptions, the claims also recite steps of detecting levels of ATTR biomarkers in blood sample of the subject. As noted above, such data gathering steps are recited at a high level of generality and are not limited, for example, to any specific or unconventional testing technique. Limitations that are necessary for all practical applications of a judicial exception, such that everyone practicing the judicial exception would be required to perform those steps or every product embodying that judicial exception would be required to include those features, would not be sufficient to confer patent eligibility. As stated supra, such additional steps/elements are also insufficient to render the claims patent-eligible because simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, has been held not to be enough to qualify as "significantly more" when recited in a claim with a judicial exception. See also Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015):
Where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent eligible subject matter if the methods themselves are conventional, routine and well understood applications in the art. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in such steps that distinguishes them from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting ATTR biomarkers using an antibody to that biomarker protein. See also MPEP 2106.05(g). Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)).
The combination of steps recited in these process claims taken as a whole, including the well-understood, routine, and conventional steps of data acquisition recited with a high level of generality which would substantially foreclose others from using the naturally occurring correlation, or limitations of the use to a particular technological environment (field-of-use) (“Guidance”, I.B.1), are not sufficient to qualify as a patent-eligible practical application of a law of nature or of a naturally occurring correlation, i.e. of a natural principle, as the claims do not amount to significantly more than a statement of the natural principle with generalized directions to apply it to the relevant population. See Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S.Ct. 1289, 101 USPQ2d 1961 (2012).
Based upon this analysis of the claims as a whole, the claims do not recite something significantly different than a judicial exception and fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
10. Claims 1, 3-15, and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arvanitis et al. (Identification of V122l (Val122lle) transthyretin cardiac amyloidosis (ATTR) using serum retinol-binding protein 4 (RBP4) and a clinical prediction model. JAMA Cardiol. 2 (3): 305-313 (2017 March 01)).
Arvanitis et al. teach a method comprising detecting and measuring a level of three (i.e. two or more) circulating transthyretin cardiac amyloidosis (ATTR, TTR-CM) biomarkers in blood samples of human (African American) subjects. The three ATTR biomarkers comprise: (i) troponin I (TnI), (ii) N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), and (iii) retinol binding protein 4 (RBP4). Arvanitis et al. teach that cTnI and NT-proBNP biomarkers are known indicators of ATTR, and that ATTR V1221 amyloidosis patients showed cTnI and NT-proBNP biomarker levels similar to those diagnosed with ATTR; hence, providing a direct correlation between cTnI and NT-proBNP biomarker levels and indication of diagnosis of ATTR V1221 amyloidosis. Arvanitis et al. further teach that RBP4 which is an endogenous TTR ligand has concentration levels that are lower in ATTR V1221 amyloidosis patients than normal subjects not having ATTR V1221 (Abstract; p. 2. 1st to 3rd full ¶s; pp. 4-7; Figure 1; Table 1). The concentration levels of the three ATTR biomarkers cTnI, NT-proBNP, and RBP4 provided an ATTR biomarker profile that were applied in an algorithm (clinical prediction algorithm model) to compute an ATTR biomarker score; wherein the algorithm is obtained from decision tree methodology using ROC analysis, logistic regressions (LASSO), and AUC scoring to provide excellent discrimination in the validation cohort for indication and/or diagnosis of transthyretin amyloid cardiomyopathy (TTR-CM: cardiac) (Abstract; p. 2. 1st to 3rd full ¶s; pp. 4-7; Figure 2). Applicant admits, by way of disclosure in paragraphs [0174] to [0195] of the specification that decision tree methodology is well known and conventionally used in the art for multiparametric data set classification models incorporating optimal biomarker threshold values in disease diagnostic studies as set forth in pages 4-7 and Figure 2 of Arvanitis et al.
With respect to claims 10 and 12, the three (two or more) ATTR biomarkers as taught by Arvanitis et al. do not comprise pyruvate kinase muscle isoform 1 (PKM1).
With respect to claims 11 and 12, the three (two or more) ATTR biomarkers as taught by Arvanitis et al. do not comprise pyruvate kinase muscle isoform 2 (PKM2).
With respect to claims 13 and 15, the three (two or more) ATTR biomarkers as taught by Arvanitis et al. do not comprise SMOC-2.
With respect to claims 14 and 15, the three (two or more) ATTR biomarkers as taught by Arvanitis et al. do not comprise DCN.
Arvanitis et al. teach that the method comprises ELISA assays using a) one or more anti-ATTR biomarker agents which are antibodies labeled with a detectable moiety (enzyme label) comprising: (i) anti-TnI antibody, (ii) anti-NT-proBNP antibody, and (iii) anti-RBP4 antibody; b) one or more control samples; and c) one or more ATTR Biomarker standards encompassed within R&D Systems (i.e. Quantikine ELISA kit) for use in in vitro diagnostic ELISA assay to diagnose TTR-CM in the subject (p. 2. 1st to 3rd full ¶s; pp. 4-7; Figure 1, Figure 2).
Accordingly, Arvanitis et al. appears to read on Applicant’s claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
11. Claims 17, 18, and 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over Arvanitis et al. (Identification of V122l (Val122lle) transthyretin cardiac amyloidosis (ATTR) using serum retinol-binding protein 4 (RBP4) and a clinical prediction model. JAMA Cardiol. 2 (3): 305-313 (2017 March 01)) in view of Boguslaski et al. (U.S. Patent 5,420,016).
Arvanitis et al. is discussed supra. Although Arvanitis et al. provide the use of R&D Systems, the reference is silent in teaching the anti-ATTR biomarker agents as enzyme labeled antibodies (labeled with a detectable moiety), controls, and ATTR biomarkers incorporated into a kit format.
Boguslaski et al. disclose incorporating various system components as well as assay reagents into a kit format (col. 7, lines 8-15).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention was to incorporate the reagents, labels, controls, and standards taught by Arvanitis into a kit arrangement as taught by Boguslaski because test kits are conventional and well known in the art for their recognized advantages of convenience and economy.
12. No claims are allowed.
Remarks
13. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Tanaka et al. (Circulating Matric Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Cardiac Amyloidosis. Journal of the American Heart Association 2 (2): 1-9 (12/03/2013) IDS) teach a method and kit comprising detecting a level of two or more transthyretin amyloidosis (ATTR) biomarkers in a blood sample of a human subject, wherein the two or more ATTR biomarkers comprise: (i) troponin I (TnI), (ii) N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), and (iii) tissue inhibitor of metalloproteinase 2 (TIMP2) (Abstract; p. 2, right col. last ¶ to p. 4; Table 1).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
July 10, 2026
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