DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
This application is the U.S. National Stage (371) application of PCT/EP2019/058222 filed on 04/02/2019 which claims priority to Foreign Application No. EP18166956.5 filed on 04/12/2018.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
Claims 1-7 and 14-16 are previously presented. Claims 8-13 are cancelled at the Applicant’s request. Claims 17-21 are withdrawn as being drawn to non-elected species as noted in the Office action of 04/15/2024.
Thus, claim 1-7 and 14-16 are under examination.
Maintained Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7, 14 and 16 are rejected under 35 U.S.C. 101 because the claimed invention is for a process or a method that is directed to at least one judicial exception without significantly more. The claims recite a mere collection of information in the form of data from which the applicant or doctor may draw an inference in light of the correlations. Such an inference is not sufficient to transform natural correlations into a patentable application.
The judicial exceptions are not integrated into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions. The claims recite several judicial exceptions, i.e., a mental process (comparing the testing value of biomarkers with a threshold value) and a law of nature (the correlation of selected biomarkers with mild or advanced periodontitis). These judicial exceptions are not integrated into a practical application because the additional limitations of the claims amount to insignificant extra-solution activity. 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).
These judicial exceptions are not integrated into a practical application because the additional limitations of the claims, i.e., the data gathering steps to identify an individual as having or being at risk of developing mild or advanced periodontitis, do not add a meaningful limitation to the method as they are insignificant extra-solution activity.
None of the dependent claims recite limitations that integrate the judicial exception into a practical application. For example, claims 3-4 are each listing the base for the threshold value to use for comparison with patient’s samples which are still not integrating the judicial exceptions into a practical application. Similarly, claims 5-6, the claims further define specific biomarkers to be tested. The correlation of PK, S100A8 and S100A9 to periodontitis is a law of nature because it describes a consequence of natural processes in the human body, e.g. the naturally-occurring relationship between the presence of PK, S100A8 and S100A9 and the manifestation of periodontitis. Thus, claims 2-3 and 5-6 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).
Moreover, the claims do not include additional elements that are sufficient to significantly amount to any added inventive concept to the judicial exceptions as detailed in MPEP § 2106.05(d). The detection and measurement of protein markers in blood is a well-understood, routine and conventional step that does not add an inventive concept to the judicial exceptions as cited above.
Per MPEP2106.05(f), another consideration when determining whether a claim integrates a judicial exception into a practical application in Step 2A Prong Two or recites significantly more than a judicial exception in Step 2B is whether the additional elements amount to more than a recitation of the words “apply it” (or an equivalent) or are more than mere instructions to implement an abstract idea or other exception on a computer. As explained by the Supreme Court; in order to make a claim directed to a judicial exception patent-eligible, the additional element or combination of elements must do “‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. 208, 221, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”).
Step 1: Is the claim to a process, machine, manufacture or composition of matter?)
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03. Regarding claims 1-7, 14 and 16 of the instant application and per Step 1, the claims are respectively directed to a statutory class of a method of “assessing whether a human patient has mild periodontitis or advanced periodontitis” or “diagnosing whether a human patient has mild periodontitis or advanced periodontitis” (Step 1: YES).
(Step 2A, Prong 1: Does the claim recite an abstract idea, law of nature or natural phenomenon?)
Regarding claims 1-7, 14 and 16 of the instant application and per Step 2A, prong 1, the claim recites a judicial exception of the claims are directed to the abstract idea of a mental process (comparing the testing value of biomarkers with a threshold value), and a law of nature (the correlation of selected biomarkers with mild or advanced periodontitis).
(Step 2A, Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?)
Regarding claims 1-7, 14 and 16 of the instant application and per Step 2A, prong 2, the claims as a whole do not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claims beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claims as a whole integrates the exception into a practical application. Claims 1 and 14 do not have additional elements that would integrate the judicial exceptions cited above into a practical application. The claims have steps of measuring a protein and assessing a pathological condition in an individual by comparing values based on the measurements. The claims have steps of measuring marker molecules at the protein level to provide values for “testing value” or “concentrations” to compare to a “threshold value” to reach a diagnosis, and these steps do not integrate the judicial exception into a practical application because they are data gathering steps to use in the calculation and comparison, which do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims only have a simple determination of a natural phenomenon and therefore, claims 1 and 14 do not integrate the judicial exceptions into a practical application.
Furthermore, the claims are only reciting “to administer at least one of a therapeutic agent or a dental procedure” without specifying the type or amount of medication nor procedure. Such steps are not sufficient to integrate the judicial exceptions into a practical application because they are too general and broad.
(Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?)
Regarding claims 1-7, 14 and 16 of the instant application and per Step 2B, this part of the eligibility analysis evaluates whether the claims as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim per MPEP 2106.05. Claims 1 and 14 of the instant application simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, such as measuring marker molecules at the protein level to provide values for a “testing value” with a commercially available assay such as detecting protein biomarkers using a commercially available test (Specification, page 10, lines 2-8 and lines 33-34). Furthermore, the claims themselves are recited at a high level of generality in which any assay can be used as the detection method for claims 1 and 14. Thus, claims 1-7, 14 and 16 are not eligible and are rejected under 35 USC 101.
Regarding claim 2, the claim further defines the health state and age of the patient which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more for the same reason as detailed above.
Regarding claims 3-4, the claims further define the threshold value which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more for the same reason as detailed above.
Regarding claims 5-6, the claims further define the claims further define the type of protein biomarkers to detect which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 7, the claim arithmetically processes the values of biomarkers which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more for the same reason as detailed above.
Regarding claim 16, the claims further define the type of disease that the patient had which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more for the same reason as detailed above.
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 (PHOSITA) 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.
Claims 1, 3-7, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Chapple et al. (WO 2014/037924 A2) in view of Krzyściak et al. (Front. Microbiol. 8:856. doi: 10.3389/fmicb.2017.00856), Larsen et al. (APMIS, 125: 376–384, 2017, APMIS. Published by John Wiley & Sons Ltd.), and Fuentes et al. (British Dental Journal, volume 217, no. 10, Nov 21 2014).
Regarding claims 1 and 14, Chapple teaches an in vitro method for assessing or diagnosing whether a human patient has mild periodontitis or advanced periodontitis (Abstract; page 2, lines 7-11; page 45, and Chapple’s claims 1 and 4).
Chapple teaches that the method comprises detecting protein biomarkers such as S100 calcium-binding protein A8 (S100A8) in from a sample of saliva from a human patient (Page 2, lines 8-11 and 17-19; page 7, lines 26-33).
Chapple teaches detecting the concentration of S100-A8 and Haemoglobin Beta (Page 2, lines 17-19; page 20, lines 30-33).
Chapple teaches detecting in a sample of saliva of the human patient the proteins S100 calcium-binding protein A8 (S100A8) (Page 2, lines 17-19; page 7, lines 26-33).
Chapple teaches determining a testing value reflecting the joint concentrations determined for protein biomarkers to form a protein profile (Page 3, “In another aspect of the method, the method further includes generating a protein profile by analyzing the proteome of the at least one oral fluid sample, and clustering the protein profile to determine a set of protein biomarkers”).
Chapple teaches assessing the presence of mild periodontitis or advanced periodontitis in the patient on the basis of the concentrations of said proteins in said sample
Chapple teaches comparing testing values of biomarkers in two data sets to come up with a threshold value that is associated with advanced periodontitis (Page 20, lines 25-34).
Chapple teaches to assess whether the testing value is indicative for mild periodontitis or for advanced periodontitis in said patient (Page 8, lines 4-13; pages 8-9, line 34 of page 8 and lines 1-2 of page 9; page 45-46, claim 15).
Chapple teaches measuring the biomarkers before and after treatment (Page 14, Table 3, “pre-treatment”, “post-treatment”).
Regarding claim 3, Chapple teaches calculating a change in the abundance of proteins from one or more samples that are used as biomarkers to serve as a threshold value and to associate such a calculation with the presence of advanced periodontitis (Page 10, lines 1-6 and lines 13-20, “According to some aspects, the method for diagnosing the status of an oral disease further includes providing the GCF and saliva sample … The selecting the set of protein biomarkers for distinguishing between particular states of periodontitis may include calculating a change in abundance of proteins …”).
Regarding claim 4, Chapple teaches calculating a change in the abundance of proteins from one or more samples that are used as biomarkers to serve as a threshold value and is based on the concentrations of the proteins in a set of samples, including samples from subjects that have mild or moderate periodontitis and samples from subjects having advanced periodontitis (Page 10, lines 1-6 and lines 13-20, “According to some aspects, the method for diagnosing the status of an oral disease further includes providing the GCF and saliva sample … The selecting the set of protein biomarkers for distinguishing between particular states of periodontitis may include calculating a change in abundance of proteins …”).
Regarding claims 5-6, Chapple teaches that the proteins comprise: PK, S100A8 and S100A9 (Page2, lines 17-19; page 20, lines 30-33; page 26, table, “Pyruvate kinase”; page 27, table, “pyruvate kinase”; page 41, supplemental table 11, “Protein S100-A9”; page 42, table, “Pyruvate kinase”).
Regarding claim 7 Chapple teaches that the concentration values of biomarkers are arithmetically processed into a number, i.e., are quantified, and thus are assigned a value between 0 and 1 (Page 17, lines 1-6, and Appendix, Supplementary Table 1 ).
Regarding claims 14 and 15, Chapple teaches a method of detecting at least one biomarker such as S100 calcium-binding protein A8 (S100A8) in a human patient for assessing or diagnosing whether a human patient has mild periodontitis or advanced periodontitis (Page2, lines 17-19; page 7, lines 20-33). Chapple teaches obtaining a saliva sample from a human patient (Page 7, lines 20-22). Chapple teaches detecting whether the proteins are present in the sample (Page 7, lines 26-29; page 8, lines 4-13). Chapple teaches contacting the sample with one or more reagents (Page 10, lines 13-16).
Regarding claim 16, Chapple teaches that the human patient is known to have periodontitis and to assess its status or level of severity (Abstract).
Regarding claims 1, 14 and 15 Chapple does not teach detecting the concentrations of Pyruvate Kinase (PK) nor of S100 calcium-binding protein A9 (S100A9) from a sample of saliva but lists PK as part of the identified proteins from gingival crevicular fluid (GCF) of patients (Page 17, lines 1-6).
Regarding claims 1, 5-6, and 14-15 Chapple does not teach that pyruvate kinase (PK) is detected with S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) but lists PK as part of the identified proteins from GCF of patients (Page 17, lines 1-6).
Regarding claim 15, Chapple does not explicitly teach contacting the sample with one or more detection reagents for binding biomarker proteins and detecting binding between each protein and with one or more detection reagents but provides a kit that includes the necessary reagents to carry out the assays for measuring different protein markers from the saliva or from GCF (Page 10, lines 13-16).
Regarding claims 1, 5-6 and 14-15, Fuentes teaches detecting the concentration of S100 calcium-binding protein A9 (S100A9) along with S100A6 and S100A8 from a sample of saliva (Page 568, middle column, last paragraph, “Other protein biomarkers in saliva for periodontal disease have recently been studied… The prominent findings were for proteins S100A6, S100A8, and S100A9 where abundance increased by fold changes of 1.64, 2.31, and 1.99, respectively.”).
Regarding claims 1, 5-6 and 14-15, Krzyściak teaches the relationship between high pyruvate kinase activity levels and cariogenic biofilm formation (Abstract).
Regarding claims 1, 5-6 and 14-15, Larsen teaches that dental biofilm causes diseases in the teeth and their supporting tissues, i.e., dental caries and periodontal diseases (Abstract; page 376, right column, second paragraph). An artisan would have been motivated to look at the activity levels or levels of pyruvate kinase (PK) in periodontal disease to further combine with S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) to provide a better prediction of periodontal disease.
It would have been obvious for a PHOSITA at the time the application was filed to combine what Fuentes, Krzyściak and Larsen taught over Chapple to improve the diagnosis and assessment of periodontal disease because Krzyściak showed the association of PK with biofilm formation (Abstract), and Larsen showed that biofilm formation can cause periodontal diseases (Abstract; page 376, right column, second paragraph). Fuentes teaches that there is an abundant increase in the levels of proteins S100A8 and S100A9 when measured in saliva of patients with periodontal disease as compared to before and after treatment (Page 568, middle column, last paragraph). Chapple offered a method for diagnosing and assessing the degree of periodontal disease using a set of protein biomarkers that vary in abundance at particular stages of Periodontitis (Abstract). Chapple suggested a need for an efficient, accurate and sensitive oral fluid diagnostic method that can diagnose and assess early and late stages of periodontal disease (Pages 1-2, lines 28-31 of page 1 and lines 1-5 of page 2). Thus, a skilled artisan would have been motivated to combine the above methods and inventions to increase the speed of detection and assessment of periodontal disease without scarifying the accuracy and sensitivity of detection. A PHOSITA would have had a reasonable expectation of success in combining the methods of Fuentes, Chapple, Krzyściak and Larsen because all of these documents disclose successful methods of measuring protein markers to assess periodontal disease.
It would have been obvious for a PHOSITA to use different biomarkers in the method of Chapple to achieve a reliable diagnosis and assessment of periodontal disease.
As stated above, Chapple lists pyruvate kinase as part of the identified proteins from GCF of patients (Page 17, lines 1-6). A skilled artisan would have been motivated to look at the activity levels or levels of pyruvate kinase (PK) in light of the teachings of Fuentes, Krzyściak and Larsen as noted above in the saliva of patients with periodontal disease to further combine with S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) to provide a specific prediction of periodontal disease.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Chapple et al. (WO 2014/037924 A2), Krzyściak et al. (Front. Microbiol. 8:856. doi: 10.3389/fmicb.2017.00856), Larsen et al. (APMIS, 125: 376–384, 2017, APMIS. Published by John Wiley & Sons Ltd.), and Fuentes et al. (British Dental Journal, volume 217, no. 10, Nov 21 2014) as applied to claim 1 above, and further in view of Bakker et al. (US 11,768,207 B2, Priority to Foreign Application: EP-17172769, May 24 of 2017).
Regarding claim 2, Chapple teaches that the human patient is known to have periodontitis (Page 2, lines 7-8; page 8, lines 18-20).
Regarding claim 2, Chapple does not teach determining the age of the human patient.
Regarding claim 2, Bakker teaches that the testing value is considered based on the age of the human subject (Abstract; column 2, lines 48-56).
Therefore, it would have been obvious for a PHOSITA at the time the application was filed to combine what Bakker taught over the methods of Chapple, Krzyściak, Larsen and Fuentes to further improve the diagnosis and assessment of periodontal disease because Bakker specified the age as an additional biomarker for the determination of the type of periodontitis (Column 3, lines 3-6; column 4, lines 10-14) to note the effect of age over the progression of periodontitis in a human subject. A PHOSITA would have had a reasonable expectation of success in combining the methods of Chapple, Krzyściak, Larsen, Fuentes and Bakker based on the methods being in the same field of measuring protein markers to assess periodontal disease.
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.
Claims 1-7 and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9-11 and 23-24 of copending Application No. 17/046,430 in view of Fuentes et al. (British Dental Journal, volume 217, no. 10, Nov 21 2014). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1 pertaining to an in vitro method for assessing whether a human patient has mild periodontitis or advanced periodontitis by detecting from a sample of saliva from a human patient the joint concentrations of proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium-binding protein A8 (S100A8) or S100 calcium-binding protein A9 (S100A9), determining a testing value based on the detected joint concentrations of the proteins, comparing the testing value with a threshold value reflecting joint concentrations of
the same proteins associated with advanced periodontitis to determine when the testing value is indicative of mild periodontitis or advanced periodontitis in the human patient and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the comparing of the testing value to the threshold value indicates advanced periodontitis, ‘430 teaches an in vitro method for assessing whether a human patient had periodontitis by detecting in a sample of saliva from the human patient, concentrations of at least three proteins, including Matrix metalloproteinase-8 (MMP-8) and two or more of Matrix metalloproteinase-9 (MMP-9), Pyruvate Kinase (PK), and S100 calcium-binding protein A8 (S100A8), determining a testing value based on a combination of the detected concentrations of the at least three proteins, comparing the testing value with a threshold value reflecting joint concentrations of the same at least three proteins associated with periodontitis to determine when the human patient has periodontitis and administering at least one of a therapeutic agent or a dental procedure to the human patient when the human patient is determined to have periodontitis (See claim 1 of ‘430).
Regarding claim 2 pertaining to determining the age of the human patient, wherein the testing value is further based on the age of the patient, ‘430 teaches that the testing value reflects the detected concentrations for the at least three proteins, in combination with an age of the human patient. (See claims 3 and 11 of ‘430).
Regarding claim 3 of the instant application pertaining to wherein the threshold value is based on the joint concentrations of the same proteins in one or more reference samples associated with presence of advanced periodontitis, ‘430 teaches that the threshold value is based on joint concentrations determined for the at least three proteins in one or more reference samples, wherein each reference sample of the one or more reference samples is associated with presence of periodontitis or absence of periodontitis (See claim 4 of ‘430).
Regarding claim 4 pertaining to that the threshold value is based on the joint concentrations of the same proteins in a set of samples, including samples from subjects having mild or moderate periodontitis and samples from subjects having advanced periodontitis, ‘430 teaches the threshold
value is based on joint concentrations of the at least three proteins in a set of samples, including samples from subjects having periodontitis and samples from subjects not having periodontitis (See claims 1 and 5 of ‘430).
Regarding claim 5 pertaining to the proteins comprising PK, S100A8 and S100A9, ‘430 teaches detecting in a sample of saliva from the human patient, concentrations of at least three
proteins, including Matrix metalloproteinase-8 (MMP-8) and two or more of Matrix metalloproteinase-9 (MMP-9), Pyruvate Kinase (PK), and S 100 calcium-binding protein A8 (S100A8) (See claims 1 and 23 of the ‘430).
Regarding claim 6 pertaining to the proteins consisting of: PK, S100A8 and S100A9; PK, Rb-beta and Rb-delta; PK, S100A8 and Rb-beta; PK, S100A8, Rb-beta and Rb-delta; PK, S100A9, Rb-beta and Rb-delta; PK, S100A8, S100A9 and Rb-beta; A1AGP, PK, S100A8 and S100A9; A1AGP, Rb-beta, Rb-delta and PK; A1AGP, PK, S100A8 and S100A9; Profilin, Rb-beta, Rb-delta and PK; or Profilin, Rb-beta, PK and S100A8, ‘430 teaches that the at least three proteins consist of Matrix metalloproteinase-8 (MMP-8), Matrix metalloproteinase-9 (MMP-9), Pyruvate Kinase (PK), and S100 calcium-binding protein A8 (S100 A8) (See claim 9 of ‘430).
Regarding claim 7 of the instant application pertaining to wherein the concentration values determined are arithmetically processed into a number between 0 and 1, ‘430 teaches that wherein the testing value is arithmetically processed into a number between 0 and 1 (See claim 10 of ‘430).
Regarding claim 14 pertaining to a method of diagnosing whether a human patient has mild periodontitis or advanced periodontitis by detecting in a sample of saliva of the human patient the proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Rb-beta), Haemoglobin- delta (Rb-delta), S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9), determining whether the human patient has mild periodontitis or advanced periodontitis based on concentrations of the proteins in the sample of saliva and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the human patient is determined to have advanced periodontitis, ‘430 teaches a method of diagnosing whether a human patient has
Periodontitis by detecting in a sample of saliva of the human patient at least three proteins
including Matrix metalloproteinase-8 (MMP-8) and two or more of Matrix metalloproteinase-
9 (MMP-9), Pyruvate Kinase (PK), and S100 calcium-binding protein A8 (S100A8), assessing presence of periodontitis in the human patient based on a combination of the detected concentrations of the at least three proteins in the sample of saliva, and administering at least one of a therapeutic agent or a dental procedure to the human patient when the presence of periodontitis is determined in the human patient (See claim 23 of ‘430).
Regarding claim 15 pertaining to a method of detecting proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S 100 calcium- binding protein A8 (S 1 00A8) and S 100 calcium-binding protein A9 (S 1 00A9) in a human patient suffering from mild or advanced periodontitis by obtaining a saliva sample from a human patient, detecting whether the proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium- binding protein A8 (S 1 00A8) and S 100 calcium-binding protein A9 (S 1 00A9) are present in the sample by contacting the sample with one or more detection reagents for binding said proteins and detecting binding between each protein and the one or more detection reagents, ‘430 teaches method of determining when a human patient has
Periodontitis by detecting in a sample of saliva from the human patient, concentrations of at least three
proteins including Matrix metalloproteinase-8 (MMP-8) and two or more of Matrix metalloproteinase-9 (MMP-9), Pyruvate Kinase (PK), and S100 calcium-binding protein A8 (S100A8) by contacting the sample with one or more detection reagents for binding the at least three proteins, and detecting binding between each protein of the at least three proteins and the one or more detection reagents (See claim 24 of ‘430).
Regarding claim 16 pertaining to that the human patient is known to have periodontitis, ‘430 teaches that the human patient is suspected to have periodontitis (See claim 2 of ‘430).
‘430 does teach detecting in a sample of saliva from the human patient the concentration of S100 calcium-binding protein A9 (S100A9) (claims 1, 5-6 and 14-15 of instant application).
Fuentes teaches detecting the concentration of S100 calcium-binding protein A9 (S100A9) along with S100A6 and S100A8 from a sample of saliva (Page 568, middle column, last paragraph, “Other protein biomarkers in saliva for periodontal disease have recently been studied… The prominent findings were for proteins S100A6, S100A8, and S100A9 where abundance increased by fold changes of 1.64, 2.31, and 1.99, respectively.”).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to add or combine testing for S100A9 with the biomarkers that ‘430 taught because Fuentes noted the prominent findings for the level of proteins of S100A6, S100A8 and S100A9 in periodontal disease (Page 568, middle column, last paragraph). The ordinary artisan would have been motivated to do so because Fuentes noted that the levels of S100A8/A9 have previously been shown in saliva to correlate with periodontitis more than S100A6 (Page 568, middle column, last paragraph). Therefore, such a combination would be considered an advantageous additive to ‘430 which also recognizes a need for improving measurements.
Claims 1-7 and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8, 21-22, 24-26, 28 and 30-33 of copending Application No. 17/046,882 in view of Fuentes et al. (British Dental Journal, volume 217, no. 10, Nov 21 2014).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1 pertaining to an in vitro method for assessing whether a human patient has mild periodontitis or advanced periodontitis by detecting from a sample of saliva from a human patient the joint concentrations of proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium-binding protein A8 (S100A8) or S100 calcium-binding protein A9 (S100A9), determining a testing value based on the detected joint concentrations of the proteins, comparing the testing value with a threshold value reflecting joint concentrations of
the same proteins associated with advanced periodontitis to determine when the testing value is indicative of mild periodontitis or advanced periodontitis in the human patient and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the comparing of the testing value to the threshold value indicates advanced periodontitis, ‘882 teaches a method for treating a human patient who has mild periodontitis or advanced periodontitis by detecting in a sample of saliva from human patient, the concentrations of the proteins: Pyruvate Kinase (PK) and at least one of Matrix metalloproteinase-9 (MMP9), S 100 calcium-binding protein A8 (S 100A8), and Hemoglobin subunit beta (Hb-beta), determining a testing value reflecting the joint concentrations determined for said proteins, comparing the testing value with a threshold value reflecting in the same manner the joint concentrations associated with advanced periodontitis, so as to assess that the testing value is indicative for mild periodontitis or for advanced periodontitis in the human patient, and administering to the human patient for which the testing value is indicative for mild periodontitis or for advanced periodontitis, an anti-microbial therapeutic agent to the gum tissue of the human patient (See claim 1 of ‘882).
Regarding claim 2 pertaining to determining the age of the human patient, wherein the testing value is further based on the age of the patient, ‘882 teaches that the age of the subject is determined and the testing value reflects the joint concentrations of proteins in combination with the age of the subject (See claims 3, 24 and 30 of ‘882).
Regarding claim 3 pertaining to that the threshold value is based on the joint concentrations of the same proteins in one or more reference samples associated with presence of advanced periodontitis, ‘882 teaches that the threshold value is based on the concentrations determined for the proteins in one or more reference samples in which each sample is associated with the presence of advanced periodontitis (See claims 4, 25 and 31 of ‘882).
Regarding claim 4 pertaining to that the threshold value is based on the joint concentrations of the same proteins in a set of samples, including samples from subjects having mild or moderate periodontitis and samples from subjects having advanced periodontitis, ‘882 teaches that the threshold value is based on the concentrations of the proteins in a set of samples, including samples from subjects that have mild or moderate periodontitis and samples from subjects having advanced periodontitis (See claims 5, 26 and 32 of ‘882).
Regarding claim 5 pertaining to the proteins comprising PK, S100A8 and S100A9, ‘882 teaches detecting in a sample of saliva from the human patient, the concentrations of the proteins: Pyruvate Kinase (PK) and at least one of Matrix metalloproteinase-9 (MMP9), S100 calcium-binding protein A8 (S100A8), and Hemoglobin subunit beta (Hb-beta) (See claims 1 and 22 of the ‘882).
Regarding claim 6 pertaining to the proteins consisting of: PK, S100A8 and S100A9; PK, Rb-beta and Rb-delta; PK, S100A8 and Rb-beta; PK, S100A8, Rb-beta and Rb-delta; PK, S100A9, Rb-beta and Rb-delta; PK, S100A8, S100A9 and Rb-beta; A1AGP, PK, S100A8 and S100A9; A1AGP, Rb-beta, Rb-delta and PK; A1AGP, PK, S100A8 and S100A9; Profilin, Rb-beta, Rb-delta and PK; or Profilin, Rb-beta, PK and S100A8, ‘882 teaches that the proteins comprise or consist of: MMP9, Hb-beta, and PK; MMP9, PK, and S100A8; and MMP9, Hb-beta, PK, and S100A8 (See claim 6 of ‘882).
Regarding claim 7 pertaining to that the determined concentration values of proteins are arithmetically processed into a number between 0 and 1, ‘882 teaches that the determined concentration values of proteins are arithmetically processed into a number between 0 and 1 (See claims 8, 28 and 33 of ‘882).
Regarding claim 14 pertaining to a method of diagnosing whether a human patient has mild periodontitis or advanced periodontitis by detecting in a sample of saliva of the human patient the proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Rb-beta), Haemoglobin- delta (Rb-delta), S100 calcium-binding protein A8 (S 100A8) and S 100 calcium-binding protein A9 (S 100A9), determining whether the human patient has mild periodontitis or advanced periodontitis based on concentrations of the proteins in the sample of saliva and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the human patient is determined to have advanced periodontitis, ‘882 teaches a method of treating a human patient who has mild periodontitis or advanced periodontitis by detecting in a sample of saliva of the human patient the proteins: Pyruvate Kinas (PK) and at least one of Matrix metalloproteinase-9 (MMP9), Si 100 calcium-binding protein A8 (Sl00A8), and Hemoglobin subunit beta (Hb-beta), determining a testing value reflecting joint concentrations determined for said proteins, assessing the presence of mild periodontitis or advanced periodontitis in the patient on the basis of the concentrations of determined proteins in tested sample, comprising comparing said determined testing value with a threshold value reflecting in the same manner the joint concentrations associated with advanced periodontitis, so as to assess whether the testing value is indicative for mild periodontitis or for advanced periodontitis in the patient, and administering, to the human patient for which the assessment is indicative for mild periodontitis or for advanced periodontitis, an anti-microbial therapeutic agent to the gum tissue of the human patient (See claim 21 of ‘882).
Regarding claim 15 pertaining to a method of detecting proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S 100 calcium- binding protein A8 (S 1 00A8) and S 100 calcium-binding protein A9 (S 1 00A9) in a human patient suffering from mild or advanced periodontitis by obtaining a saliva sample from a human patient, detecting whether the proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium- binding protein A8 (S 1 00A8) and S 100 calcium-binding protein A9 (S 1 00A9) are present in the sample by contacting the sample with one or more detection reagents for binding said proteins and detecting binding between each protein and the one or more detection reagents, ‘882 teaches a method of treating periodontitis by detecting the proteins: Pyruvate Kinase (PK) and at least one of Matrix metalloproteinase-9 (MMP9), Sl00 calcium-binding protein A8 (Sl00A8), and Hemoglobin subunit beta (Hb-beta) in a human patient by obtaining a saliva sample from a human patient, detecting whether the proteins are present in the sample by contacting the sample with one or more detection reagents for binding said proteins and detecting binding between each protein and the one or more detection reagents (See claim 22 of ‘882).
Regarding claim 16, Regarding claim 16 pertaining to that the human patient is known to have periodontitis, ‘882 teaches that the human patient is known to have periodontitis (See claim 2 of ‘882).
‘882 does not teach detecting in a sample of saliva from the human patient the concentration of S100 calcium-binding protein A9 (S100A9) (claims 1, 5-6 and 14-15 of instant application)
Fuentes teaches detecting the concentration of S100 calcium-binding protein A9 (S100A9) along with S100A6 and S100A8 from a sample of saliva (Page 568, middle column, last paragraph, “Other protein biomarkers in saliva for periodontal disease have recently been studied… The prominent findings were for proteins S100A6, S100A8, and S100A9 where abundance increased by fold changes of 1.64, 2.31, and 1.99, respectively.”).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to add or combine testing for S100A9 with the biomarkers that ‘882 taught because Fuentes noted the prominent findings for the level of proteins of S100A6, S100A8 and S100A9 in periodontal disease (Page 568, middle column, last paragraph). The ordinary artisan would have been motivated to do so because Fuentes noted that the levels of S100A8/A9 have previously been shown in saliva to correlate with periodontitis more than S100A6 (Page 568, middle column, last paragraph). Therefore, such a combination would be considered an advantageous additive to ‘882 which also recognizes a need for improving measurements.
Claims 1-7 and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 11 and 22-24 of copending Application No. 16/962,246 in view of Fuentes et al. (British Dental Journal, volume 217, no. 10, Nov 21 2014).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1 pertaining to an in vitro method for assessing whether a human patient has mild periodontitis or advanced periodontitis by detecting from a sample of saliva from a human patient the joint concentrations of proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium-binding protein A8 (S100A8) or S100 calcium-binding protein A9 (S100A9), determining a testing value based on the detected joint concentrations of the proteins, comparing the testing value with a threshold value reflecting joint concentrations of the same proteins associated with advanced periodontitis to determine when the testing value is indicative of mild periodontitis or advanced periodontitis in the human patient and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the comparing of the testing value to the threshold value indicates advanced periodontitis, ‘246 teaches a method for treating gingivitis and/or periodontitis in a human patient based on assessing that the human patient has gingivitis, has mild periodontitis, or has advanced periodontitis by detecting in a sample of saliva from said human patient, a concentration of the proteins: Alpha-1-acid glycoprotein (A1AGP) and Pyruvate Kinase (PK), and at least one of the proteins Matrix metalloproteinase-9 (MMP-9) and S100 calcium binding protein A8 (S100A8), determining at least one testing value reflecting a joint concentration determined for said proteins, determining that the testing value is indicative for one or more of gingivitis, mild periodontitis, and advanced periodontitis in said patient and administering, based on determining that the testing value is indicative for one or more of gingivitis, mild periodontitis, and advanced periodontitis in said patient, a treatment for the gingivitis and/or periodontitis in the human patient wherein the administered treatment comprises one or more of an administered therapeutic agent and an administered dental procedure (See claims 1, 11 and 23 of the ‘246).
Regarding claim 2 pertaining to determining the age of the human patient, wherein the testing value is further based on the age of the patient, ‘246 teaches that the age of the subject is determined and the testing value reflects the joint concentrations determined for said proteins in combination with the determined age of the subject (See claim 5 of ‘246).
Regarding claim 3 pertaining to that the threshold value is based on the joint concentrations of the same proteins in one or more reference samples associated with presence of advanced periodontitis, ‘246 teaches that the threshold value is based on the concentrations determined for the proteins in one or more reference samples each sample associated with the presence of healthy gums, gingivitis, mild periodontitis, or advanced periodontitis (See claim 5 of ‘246).
Regarding claim 4 pertaining to that the threshold value is based on the joint concentrations of the same proteins in a set of samples, including samples from subjects having mild or moderate periodontitis and samples from subjects having advanced periodontitis, ‘246 teaches that the threshold value is based on the concentrations determined for the proteins in one or more reference samples each sample associated with the presence of healthy gums, gingivitis, mild periodontitis, or advanced periodontitis (See claims 2 and 5 of ‘246).
Regarding claim 5 pertaining to the proteins comprising PK, S100A8 and S100A9, ‘246 teaches detecting in a sample of saliva from said human patient, a concentration of the proteins: Alpha-1-acid glycoprotein (A1AGP) and Pyruvate Kinase (PK), and at least one of the proteins Matrix metalloproteinase-9 (MMP-9) and S100 calcium binding protein A8 (S100A8) (See claims 1, 11 and 23-24 of the ‘246).
Regarding claim 6 pertaining to the proteins consisting of: PK, S100A8 and S100A9; PK, Rb-beta and Rb-delta; PK, S100A8 and Rb-beta; PK, S100A8, Rb-beta and Rb-delta; PK, S100A9, Rb-beta and Rb-delta; PK, S100A8, S100A9 and Rb-beta; A1AGP, PK, S100A8 and S100A9; A1AGP, Rb-beta, Rb-delta and PK; A1AGP, PK, S100A8 and S100A9; Profilin, Rb-beta, Rb-delta and PK; or Profilin, Rb-beta, PK and S100A8, ‘246 teaches that the proteins comprise or consist of: Alpha-1-acid glycoprotein (A1AGP) and Pyruvate Kinase (PK), and at least one of the proteins Matrix metalloproteinase-9 (MMP-9) and S100 calcium binding protein A8 (S100A8) (See claims 1, 11 and 22-24 of ‘246).
Regarding claim 7 pertaining to that the determined concentration values of proteins are arithmetically processed into a number between 0 and 1, ‘246 teaches that the concentration values determined are arithmetically processed into a number between 0 and 1 (See claim 5 of ‘246).
Regarding claim 14 pertaining to a method of diagnosing whether a human patient has mild periodontitis or advanced periodontitis by detecting in a sample of saliva of the human patient the proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Rb-beta), Haemoglobin- delta (Rb-delta), S100 calcium-binding protein A8 (S 100A8) and S 100 calcium-binding protein A9 (S 100A9), determining whether the human patient has mild periodontitis or advanced periodontitis based on concentrations of the proteins in the sample of saliva and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the human patient is determined to have advanced periodontitis, ‘246 teaches a method for treating periodontitis in a human patient based on diagnosing that the human patient is has gingivitis, has mild periodontitis, or has advanced periodontitis by detecting in a sample of saliva of the human patient concentrations of the proteins Alpha-1-acid glycoprotein (A1AGP) and Pyruvate Kinase (PK), and at least one of the proteins Matrix metalloproteinase-9 (MMP-9) and S100 calcium binding protein A8 (S100A8), assessing a presence of gingivitis, mild periodontitis, or advanced periodontitis in the patient on the basis of the detected concentrations of said proteins in said sample and administering, based on the assessed presence of gingivitis, mild periodontitis, or advanced periodontitis in the patient, a treatment for the gingivitis, mild periodontitis, or advanced periodontitis (See claim 23 of ‘246).
Regarding claim 15 pertaining to a method of detecting proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium- binding protein A8 (S 100A8) and S100 calcium-binding protein A9 (S100A9) in a human patient suffering from mild or advanced periodontitis by obtaining a saliva sample from a human patient and detecting whether the proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium- binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100 A9) are present in the sample by contacting the sample with one or more detection reagents for binding said proteins and detecting binding between each protein and the one or more detection reagents, ‘246 teaches a method of detecting proteins Alpha-1-acid glycoprotein (A1AGP) and Pyruvate Kinase (PK), and at least one of proteins Matrix metalloproteinase-9 (MMP-9) and S100 calcium binding protein A8 (S100A8) in a human patient suffering from gingivitis, mild periodontitis or advanced periodontitis, by obtaining a saliva sample from the human patient and detecting whether Alpha-1-acid glycoprotein (A1AGP) and Pyruvate Kinase PK), and at least one of Matrix metalloproteinase-9 (MMP-9) and S100 calcium binding protein A8 (S100A8) are present in the sample by contacting the sample with one or more detecting reagents for binding said proteins and detecting binding between each protein and the one or more detecting reagents (See claim 24 of ‘246).
Regarding claim 16 pertaining to that the human patient is known to have periodontitis, ‘246 teaches periodontal disease (See claim 5 of ‘246).
Regarding claim 1, 5 and 14-15 of the instant application, ‘246 does not teach detecting in a sample of saliva from the human patient the concentration of S100 calcium-binding protein A9 (S100A9).
Fuentes teaches detecting the concentration of S100 calcium-binding protein A9 (S100A9) along with S100A6 and S100A8 from a sample of saliva (Page 568, middle column, last paragraph, “Other protein biomarkers in saliva for periodontal disease have recently been studied… The prominent findings were for proteins S100A6, S100A8, and S100A9 where abundance increased by fold changes of 1.64, 2.31, and 1.99, respectively.”).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to add or combine testing for S100A9 with the biomarkers that ‘246 taught because Fuentes noted the prominent findings for the level of proteins of S100A6, S100A8 and S100A9 in periodontal disease (Page 568, middle column, last paragraph). The ordinary artisan would have been motivated to do so because Fuentes noted that the levels of S100A8/A9 have previously been shown in saliva to correlate with periodontitis more than S100A6 (Page 568, middle column, last paragraph). Therefore, such a combination would be considered an advantageous additive to ‘246 which also recognizes a need for improving measurements.
Claims 1-7 and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-10 of copending Application No. 17/046,361 in view of Fuentes et al. (British Dental Journal, volume 217, no. 10, Nov 21 2014).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1 pertaining to an in vitro method for assessing whether a human patient has mild periodontitis or advanced periodontitis by detecting from a sample of saliva from a human patient the joint concentrations of proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium-binding protein A8 (S100A8) or S100 calcium-binding protein A9 (S100A9), determining a testing value based on the detected joint concentrations of the proteins, comparing the testing value with a threshold value reflecting joint concentrations of the same proteins associated with advanced periodontitis to determine when the testing value is indicative of mild periodontitis or advanced periodontitis in the human patient and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the comparing of the testing value to the threshold value indicates advanced periodontitis, ‘361 teaches an in vitro method for assessing or predicting the response of a human patient suffering from periodontal disease to treatment of that periodontal disease by detecting at a first point in time, in a sample of saliva from said human patient suffering from periodontal disease, concentrations for each of the proteins: (i) Hemoglobin subunit delta (Rb-delta) and Pyruvate kinase (PK); or (ii) Keratin-4 (K-4) and at least two of Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK),. and Matrix metalloproteinase-8 (MMP-8); or (iii) Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK)., and S100 calcium binding protein A8 (S100A8), determining at least one pre-treatment testing value reflecting a joint concentration of the proteins based on the concentrations determined for each of said proteins at the first point in time, determining, in a sample of saliva from said human patient, concentrations for each of the proteins used to determine the pre-treatment testing value at a second point in time after said human patient has been provided with one or more treatments for periodontal disease; determining at least one post-treatment testing value reflecting a joint concentration of the proteins based on the concentrations determined for each of said proteins, at the second point in time; determining a treatment efficacy value associated with the human patient based on a comparison between the pre-treatment testing value and the post-treatment testing value; and comparing said treatment efficacy value with a threshold value reflecting in the same manner a change in joint protein concentrations associated with successful treatment of periodontal disease, so as to assess whether the treatment efficacy value is indicative for successful treatment of periodontal disease in said patient (See claim 1 of the ‘361).
Regarding claim 2 pertaining to determining the age of the human patient, wherein the testing value is further based on the age of the patient, ‘361 teache3s that the age of the subject is determined and the treatment efficacy value reflects the joint concentrations determined for said proteins in combination with the age of the subject (See claim 7 of ‘361).
Regarding claim 3 pertaining to that the threshold value is based on the joint concentrations of the same proteins in one or more reference samples associated with presence of advanced periodontitis, ‘361 teaches that the threshold value is based on the concentration or concentrations determined for the proteins in one or more reference samples each sample associated with the successful treatment of periodontitis or the unsuccessful treatment of periodontitis (See claim 8 of ‘361).
Regarding claim 4 pertaining to that the threshold value is based on the joint concentrations of the same proteins in a set of samples, including samples from subjects having mild or moderate periodontitis and samples from subjects having advanced periodontitis, ‘361 teaches that threshold value is based on the concentration or concentrations determined for the proteins in one or more reference samples each sample associated with the successful treatment of periodontitis or the unsuccessful treatment of periodontitis (See claim 8 of ‘361).
Regarding claim 5 pertaining to the proteins comprising PK, S100A8 and S100A9, ‘361 teaches that the concentrations of the proteins Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK) and S100 calcium binding protein A8 (S100A8) are detected (See claim 6 of ‘361).
Regarding claim 6 pertaining to the proteins consisting of: PK, S100A8 and S100A9; PK, Rb-beta and Rb-delta; PK, S100A8 and Rb-beta; PK, S100A8, Rb-beta and Rb-delta; PK, S100A9, Rb-beta and Rb-delta; PK, S100A8, S100A9 and Rb-beta; A1AGP, PK, S100A8 and S100A9; A1AGP, Rb-beta, Rb-delta and PK; A1AGP, PK, S100A8 and S100A9; Profilin, Rb-beta, Rb-delta and PK; or Profilin, Rb-beta, PK and S100A8, ‘361 teaches that the concentrations of the proteins Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK) and S100 calcium binding protein A8 (S100A8) are detected (See claim 6 of ‘361).
(See claims 6 of ‘361).
Regarding claim 7 pertaining to that the determined concentration values of proteins are arithmetically processed into a number between 0 and 1, ‘361 teaches that the concentration values determined for each of the proteins are arithmetically processed into a number between 0 and 1 (See claim 10 of ‘361).
Regarding claim 14 pertaining to a method of diagnosing whether a human patient has mild periodontitis or advanced periodontitis by detecting in a sample of saliva of the human patient the proteins Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Rb-beta), Haemoglobin- delta (Rb-delta), S100 calcium-binding protein A8 (S 100A8) and S 100 calcium-binding protein A9 (S 100A9), determining whether the human patient has mild periodontitis or advanced periodontitis based on concentrations of the proteins in the sample of saliva and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the human patient is determined to have advanced periodontitis, ‘361 teaches a method for assessing or predicting the response of a human patient suffering from periodontal disease to treatment of that periodontal disease by detecting at a first point in time, in a sample of saliva from said human patient suffering from periodontal disease, concentrations for each of the proteins: (i) Hemoglobin subunit delta (Rb-delta) and Pyruvate kinase (PK); or (ii) Keratin-4 (K-4) and at least two of Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK),. and Matrix metalloproteinase-8 (MMP-8); or (iii) Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK)., and S100 calcium binding protein A8 (S100A8), determining at least one pre-treatment testing value reflecting a joint concentration of the proteins based on the concentrations determined for each of said proteins at the first point in time, determining, in a sample of saliva from said human patient, concentrations for each of the proteins used to determine the pre-treatment testing value at a second point in time after said human patient has been provided with one or more treatments for periodontal disease; determining at least one post-treatment testing value reflecting a joint concentration of the proteins based on the concentrations determined for each of said proteins, at the second point in time; determining a treatment efficacy value associated with the human patient based on a comparison between the pre-treatment testing value and the post-treatment testing value; and comparing said treatment efficacy value with a threshold value reflecting in the same manner a change in joint protein concentrations associated with successful treatment of periodontal disease, so as to assess whether the treatment efficacy value is indicative for successful treatment of periodontal disease in said patient (See claim 1 of the ‘361).
Regarding claim 15 pertaining to a method of detecting proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium- binding protein A8 (S 100A8) and S100 calcium-binding protein A9 (S100A9) in a human patient suffering from mild or advanced periodontitis by obtaining a saliva sample from a human patient and detecting whether the proteins consisting of Pyruvate Kinase (PK) and at least two of Haemoglobin-beta (Hb-beta), Haemoglobin-delta (Hb-delta), S100 calcium- binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100 A9) are present in the sample by contacting the sample with one or more detection reagents for binding said proteins and detecting binding between each protein and the one or more detection reagents, ‘361 teaches a method of detecting the concentrations of (i) Hemoglobin subunit delta (Rb-delta) and Pyruvate kinase (PK); or (ii) Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK), and S100 calcium binding protein A8 (S100A8); or (iii) Keratin-4 (K-4), Alpha-1-acid glycoprotein (A1AGP), and Pyruvate Kinase (PK); or (iv) Keratin-4 (K-4).,_ Alpha-1-acid glycoprotein (A1AGP), and Matrix metalloproteinase-8 (MMP-8); or (v) Keratin-4 (K-4), Pyruvate Kinase (PK), and Matrix metalloproteinase-8 (MMP-8); or (vi) Keratin-4 (K-4), Alpha-1-acid glycoprotein (A1AGP), Pyruvate Kinase (PK), and Matrix metalloproteinase-8 (MMP-8) (See claim 9 of ‘361).
Regarding claim 16 pertaining to that the human patient is known to have periodontitis, ‘361 teaches a human patient having periodontal disease (See claim 1 of ‘361).
Regarding claims 1, 5 and 14-15 of the instant application, ‘361 does not teach detecting in a sample of saliva from the human patient the concentration of S100 calcium-binding protein A9 (S100A9).
Fuentes teaches detecting the concentration of S100 calcium-binding protein A9 (S100A9) along with S100A6 and S100A8 from a sample of saliva (Page 568, middle column, last paragraph, “Other protein biomarkers in saliva for periodontal disease have recently been studied… The prominent findings were for proteins S100A6, S100A8, and S100A9 where abundance increased by fold changes of 1.64, 2.31, and 1.99, respectively.”).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to add or combine testing for S100A9 with the biomarkers that ‘361 taught because Fuentes noted the prominent findings for the level of proteins of S100A6, S100A8 and S100A9 in periodontal disease (Page 568, middle column, last paragraph). The ordinary artisan would have been motivated to do so because Fuentes noted that the levels of S100A8/A9 have previously been shown in saliva to correlate with periodontitis more than S100A6 (Page 568, middle column, last paragraph). Therefore, such a combination would be considered an advantageous additive to ‘361 which also recognizes a need for improving measurements.
Response to Arguments
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive.
Rejection of claims under 35 U.S.C. 101:
Regarding the rejection of claims 1-7 and 14 under 35 U.S.C. 101, Applicant noted that the amended claims are directed to specific combinations of proteins that are used to determine a testing value, which is not a law of nature. The Applicant further alleges that determining the presence of mild or advanced periodontitis is done by comparing the determined testing value with a threshold value that reflects joint concentrations of the same proteins, which is also not a law of nature. However, the claims are still directed to a law of nature (the correlation of selected biomarkers with mild or advanced periodontitis) because the selected biomarkers are joined in a general manner and according to broadest reasonable interpretation multiple combinations can exist. The Applicant does not define how the proteins are going to be joined and at what step. Furthermore, the claims are still directed to a mental process (comparing the testing value of biomarkers with a threshold value). It is irrelevant whether the claims are directed to measurement of specific combinations of biomarkers for diagnosis of disease. The specific combination of biomarkers recited by the claims and their relationship with mild and/or advanced periodontitis is part of the judicial exception(s) of the claims themselves. One cannot rely on a judicial exception itself to provide either a practical application of a judicial exception or significantly more than a judicial exception. These natural correlations between the biomarkers recited by the claims and periodontitis status merely reflect what is happening in nature without any inventive contribution by application.
The Applicant still compared the claims of the instant application to the claims that were addressed by Federal Circuit in in Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1048-49, 119 USPQ2d 1370, 1374 (Fed. Cir. 2016), which determined that claims reciting process steps of fractionating, recovering, and cryopreserving hepatocytes are not directed to laws of nature "because they are not focused on merely observing or detecting the ability of hepatocytes to survive multiple freeze-thaw cycles." See MPEP 2106.04(b)(I). Such a comparison is still void because in the instant case, the claims are looking at levels of proteins and drawing conclusion based on their levels. The claims do not teach a new technique or technology as in the steps of fractionating, recovering and cryopreserving hepatocytes as in the case of Rapid Litig. Mgmt. v. CellzDirect. The claims of the instant application are simply reciting a judicial exception without integrating it into a practical application.
Second, The Applicant still argued that claim 1 integrates any potential abstract idea into at least the practical applications of determining when the testing value is indicative of mild periodontitis or advanced periodontitis in the human patient based on the comparison of the testing value to a threshold value, and determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the comparing of the testing value to the threshold value indicates advanced periodontitis. The Applicant cited MPEP 2106.04(b)(I) “For example, claims reciting a naturally occurring relationship between a patient's genotype and the risk of QTc prolongation (a law of nature) were held eligible as not 'directed to' that relationship because they also recited a step of treating the patient with an amount of a particular medication that was tailored to the patient's genotype." (citing Vanda Pharm. Inc. v. West-Ward Pharm. Int'l Ltd., 887 F.3d 1117, 1134-36, 126 USPQ2d 1266, 1279-81 (Fed. Cir. 2018))”. However, the MPEP notes that the amount and type of the medication were tailored according to the patient’s genotype. In the instant application, the claims are only reciting “determining to administer at least one of a therapeutic agent or a dental procedure” without specifying the type or amount of medication nor procedure. See MPEP 2106.04(d)(2), which states that any added treatment step must be particular and specific to provide a practical application of a judicial exception(s).
Also, the treatment step that is offered is conditional because it depends on comparing the testing value of biomarkers to the threshold value to indicate advanced periodontitis. Thus, a patient might not be treated if not diagnosed with advanced periodontitis.
Third, the Applicant still argued that the claimed process is an improvement to the technical medical field of using protein biomarkers for detection of disease. However, the claims are simply reciting a judicial exception in a different manner from what it is recited and without introducing a new technique, instrument or improvement for example. As stated in the patent law “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”.
Thus, the previous rejection of claims 1-7, 14, and 16 under 35 U.S.C. 101, regarding the claims directed to at least one judicial exception without significantly more, is maintained.
Rejection of Claims under 35 U.S.C. 103:
The Applicant argued that Reference Chapple is not teaching certain limitations of claim 1. Specifically, the Applicant argued that Chapple does not teach the limitation “determining to administer at least one of a therapeutic agent or a dental procedure to the human patient when the comparing of the testing value to the threshold value indicates advanced periodontitis”. The Applicant further argued that the Office action is citing irrelevant teaching of “measuring biomarkers before after treatment”.
Last, the Applicant argued that Table 3 as cited in the Office action, does not even show measuring biomarkers of patients before and after treatment and that the Table shows six different groups of patients having different states of oral disease.
This argument is not persuasive because Chapple teaches that 6 x 1.5 mL "population" samples were available for proteomic analysis by MS as indicated in Table 3 (Page 13, last paragraph; page 14, first paragraph). Table 3 is not just simply about listing group of patients. Furthermore, Chapple is comparing two types of samples to teach which biomarkers vary in abundance at particular stages of periodontitis. Chapple teaches a set of protein biomarkers to identify and quantify in expression in an acquired gingival crevicular fluid (GCF) or saliva oral fluid sample in order to distinguish
between different states of periodontitis (Abstract). Chapple is comparing the protein markers before and after treatment to identify such biomarkers.
The Applicant argued that Chapple does not teach detecting at least two of Hb-beta, Hb-delta, S100A8 and S100A9, in addition to PK, as recited in claim 1. The Applicant argued that Chapple does not teach PK, and the use of closed ended language of “consisting of” does not allow to include additional proteins such as PK in the group of proteins.
This argument is not persuasive because Chapple is not part of a 102 rejection. The Applicant is reminded to look at the teachings of references in combination as it has been noted in the MPEP. Regarding the rejection of claims under 35 U.S.C. 103 and in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, the references of Chapple, Krzyściak, Larsen, and Fuentes teach the biomarkers of the instant application in combination as discussed above.
The Applicant argued that Chapple does not indicate what proteins may be detected and in what combination to indicate mild periodontitis versus advanced periodontitis.
This argument is not persuasive because the claims are recited in a generic manner and do not indicate how to differentiate each type of periodontitis. Furthermore, Chapple clearly teaches a set of protein biomarkers to identify and quantify in expression in an acquired gingival crevicular fluid (GCF) or saliva oral fluid sample in order to distinguish between different states of periodontitis (Abstract).
The Applicant argued that Chapple does not teach a threshold value.
This argument is not true as Chapple clearly teaches the concept of a threshold (Page 6, last paragraph; page 7, first, second and third paragraphs). Chapple further teaches the that there is a large increase in the levels of hemoglobin beta and S100-A8 between mild and severe periodontitis (Page 21, lines 13-19 and 28-33). Last, Chapple teaches that all proteins show ratios relative to a healthy control group (Page 17, line 4).
The Applicant argued against Krzyściak for being directed to only teaching PK and not in combination with any other protein and against Larsen for not mentioning any of the proteins recited in claim 1, including PK, in any context.
This argument is not persuasive because both Krzyściak and Larsen are used as secondary references. Also, as noted above, references are not to be looked at individually in a 103 rejection.
The Applicant argued that it is not sufficient to simply show that the proteins of claim 1, i.e., PK and at least two of Hb-beta, Hb-delta, S100A8 or S100A9, existed in the prior art because there must also be a rational basis for a skilled artisan to combine the proteins in a specific manner as specified by claim 1. And the Office action has failed to provide such a rationale for the combination of proteins.
The Applicant further argued that the proposed combination of Chapple and Krzyściak is improper because there is no rational basis for combining the respective teaches and no reasonable expectation of success in doing so.
This argument is not persuasive because in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Chapple is teaching the use of biomarkers to differentiate between mild and severe periodontitis and Fuentes teaches using salivary diagnostics with biomarkers for periodontal disease and for treatment planning. Both Krzyściak and Larsen in combination teaches the importance of using PK for the progression of periodontal disease. Thus, a skilled artisan would have been motivated with the teachings of Chapple, Krzyściak, Larsen and Fuentes to arrive at the invention of the instant application.
Also, in response to applicant's argument that Krzyściak is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Krzyściak is teaching the relationship between Pyruvate Kinase activity and cardiogenic biofilm formation which causes diseases in the teeth and their supporting tissues, i.e., dental caries and periodontal diseases as noted by Larsen (Abstract; page 376, right column, second paragraph). An artisan would have been motivated to look at the activity levels or levels of pyruvate kinase (PK) in periodontal disease to further combine with S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) to provide a better prediction of periodontal disease.
The Applicant argued against submitting a terminal disclaimer to overcome the non-statutory double patenting rejection of claims because the Applicant argued that the Examiner did not indicate allowing the claims if a terminal disclaimer is submitted .
This argument is not persuasive because 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).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OMAR RAMADAN whose telephone number is (571)270-0754. The examiner can normally be reached Monday-Friday 8:30 am - 5:00 pm.
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, Gregory 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights