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 .
Status of Claims
Claims 1, 2, 5, 11, 22-24, and 26-32 were pending. Claim 32 is canceled.
Claims 1, 2, 5, 11, 22-24, and 26-31 are examined.
Withdrawn Rejections
The rejection of claim 24 under 112(a) is withdrawn in view of Applicant’s arguments.
The rejection of claim 32 is withdrawn in view of claim cancellation.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL. —The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 5, 11, 22-23, and 26-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 1, 11, and 22-23 recite the following methods:
Claim 1 – (a) 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 … (b) 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;
Claim 11 – (a) a method for treating gingivitis and/or periodontitis in a human patient based on assessing that the patient has gingivitis, has mild periodontitis, or has advanced periodontitis … (b) calculating a single joint testing value reflecting the detected concentrations of the set of proteins; comparing the calculated single joint testing value to a predetermined threshold;
Claim 22 – (a) a method for treating gingivitis and/or periodontitis in a
human patient … (b) comparing the detected concentrations at time point ti to the detected concentrations at time point t2 to determine a difference in the detected concentrations, whereby the determined difference in the concentrations reflects a change in status of periodontal disease in the human patient;
Claim 23 – (a) 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 … (b) 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.
All four claims share the following common limitations: (a) a method for treating and (b) a condition determined from detecting concentrations of the following combinations of proteins: A1AGP, PK, and MMP-9; or A1AGP, PK, and S100A8.
The specification discloses the recited methods in some details providing alternative combinations of the biomarkers (pg. 7, lines 6-15); saliva sample volumes (pg. 7, lines 26-30); a definition of the term “concentration” (pg. 9, lines 3-8); immunoassay formats (pg. 9, lines 26-34); other methods of protein quantitation (pg. 10, lines 25-34); specific assay conditions (pg. 11, par. 1-2); various ways of calculating the conditions for initiating the recited treatments (pg. 12, lines 16-34 – pg. 14, lines 1-24); specific calculation of the scores (pg. 17, lines 23-32).
However, the specification fails to disclose specific values, ranges, or parameters for calculations of the conditions for initiating treatments.
Claim 1 recites determining at least one testing value reflecting a joint concentration determined for said proteins; and claim 11 - calculating a single joint testing value reflecting the detected concentrations of the set of proteins. The specification discloses only very high-level ideas for calculating the testing value without providing any specific formulas, examples of testing value numerical values, or ranges: “The method of the invention comprises determining at least one testing value reflecting the joint concentrations measured for said proteins. A joint concentration value can be any value obtained by input of the concentrations as determined and an arithmetic operation of these values. This can, e.g., be a simple addition of the concentrations. It can also involve multiplying each concentration with a factor reflecting a desired weight of these concentrations, and then adding up the results” (pg. 12, lines 14-21).
The calculation instructions for the joint concentration value are disclosed at very high-level as following: “based on the protein concentrations, three scores (between 0 and 1) can be calculated:
SP: this can be considered to be the probability of periodontitis 'versus' health/ gingivitis
SG: this can be considered to be the probability of gingivitis ·versus' health
SAP: this can be considered to be the probability of advanced periodontitis "versus' mild periodontitis
The probabilities (between O and 1) of the four disease stages may then be calculated as follows:
• Health (H): (l-Sp )·(1-SG)
• Gingivitis (G): (l-Sp)·SG
• Mild Periodontitis (MP): Sp·(l-SAP)
• Advanced Periodontitis (AP): Sp·(SAP)” (pg. 13, line 30 – pg. 14, line 10).
The disclosed instruction are very high-level ideas without specific values for the four key conditions: H, G, MP, and AP.
There is only one example disclosed in the specification (starting on pg. 21, line 8). However, the example fails to disclose specific values, ranges, or parameters for calculation of the conditions for initiating the recited treatments.
Table 1 and pg. 21, lines 30-34 disclose ROC AUC values, but these values do not translate into the recited testing value of claim 1, a single joint testing value of claim 11, comparing the detected concentrations at time point t1 to the detected concentrations at time point t2 of claim 22, or 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 of claim 23. In fact, the ROC AUC values are not linked to the claimed subject matter and are not recited in the claims.
The level of one of ordinary skill is high with an ordinary practitioner possessing a PhD and related post-doctoral research experience, but the lack of the prior art teachings on the claimed biomarker combinations requires more specific and detailed disclosure from the inventor.
Claims 2, 5, and 26-31 are rejected as being dependent from the rejected base claims 1, 11, and 22-23.
Therefore, based on the above findings, one of ordinary skill in the art would conclude that Applicant did not have possession of the claimed invention.
Response to Arguments
Applicant's arguments filed April 28, 2026 have been fully considered.
Claims 1, 2, 5, 11, 22-24, and 26-31 were rejected under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement.
Applicant argues that “present specification provides ample written-description support for claims 1, 11, 22-24, and 26-31” (pg. 7, par. 4) and “also defines "concentration," discusses direct and indirect measurement, and describes detection reagents and specific binding. Thus, the application does not merely announce a research goal; it discloses the exact biomarker panels, sample type, assay framework, and disease-state outputs that are now claimed (pg. 7, last par. – pg. 8, par. 1).
The arguments are not persuasive because the rejection (non-final OA; January 28, 2026) pointed out specific information that was missing in the specification: “the specification fails to disclose specific values, ranges, or parameters for calculations of the conditions for initiating the recited treatments” (OA, pg. 4, par. 2). Applicant’s argument fails to overcome the rejection because “ample written-description support” and “exact biomarker panels, sample type, assay framework, and disease-state outputs” do not address missing “specific values, ranges, or parameters for calculations” stated in the rejection.
Applicant argues that “The claims do not require any one fixed numerical threshold, any one exclusive mathematical formula, or any single mandatory classification algorithm. Rather, the claims require the use of the disclosed biomarker combinations to determine a testing value or disease-state assessment.” (pg. 8, par. 2).
The argument is not persuasive because the rejection indicates lack of evidence for “specific values, ranges, or parameters for calculations” in the entire disclosure of the invention, not just claims.
Applicant argues that “the application explains that a joint concentration value may be obtained from the detected biomarker concentrations by arithmetic processing, including addition, weighted addition, multiplication, division, subtraction, exponentiation, or combinations thereof. The application further discloses that the resulting joint concentration value may be compared with one or more threshold values reflecting the joint concentrations associated with the disease states of interest. It also explains that threshold values may be derived from reference samples associated” (pg. 8, par. 2).
The argument is not persuasive because the phrase “may be” is used to indicate that something is possible but not certain. Therefore, “may be” obtained, compared, or derived is not sufficient for one of ordinary skill in the art to conclude that Applicant indeed had possession of the claimed invention at the time the application was originally filed.
Applicant argues that “the application discloses generating disease-related scores for periodontitis versus health/gingivitis, gingivitis versus health, and advanced periodontitis versus mild periodontitis, and using those scores to determine probabilities for the four disease stages” (pg. 8, par. 3).
The argument is not persuasive because the application does not disclose disease-related scores for the four key health conditions Sp, Sg, and Sap, or how they are generated. As was presented in 112(a) rejection “The specification discloses only very high-level ideas for calculating the testing value without providing any specific formulas, examples of testing value numerical values, or ranges: “The method of the invention comprises determining at least one testing value reflecting the joint concentrations measured for said proteins. A joint concentration value can be any value obtained by input of the concentrations as determined and an arithmetic operation of these values. This can, e.g., be a simple addition of the concentrations. It can also involve multiplying each concentration with a factor reflecting a desired weight of these concentrations, and then adding up the results” (pg. 12, lines 14-21)” (OA, pg. 4, par. 3). Please, note the phrases “can be” do not necessarily disclose something known.
Applicant argues that “disclosure more than reasonably conveys possession of the claimed biomarker-based classification framework” (pg. 8, par. 3), “the specification, as filed, identifies specific marker panels, the saliva-based detection approach, the joint-concentration/testing-value concept, threshold-based classification, decision tree analysis, and a specific trained classifier framework, all tied to the exact disease states now claimed” (pg. 8, last par. – pg. par. 1); “The "Summary of the Invention" expressly discloses determining a change in status of periodontal disease over a time interval from a first time point to a second later time point by detecting the concentrations of A1AGP, PK, and at least one of S100A8 and MMP-9 in saliva at both time points and comparing those concentrations, whereby a difference reflects a change in status” (pg. 9, par. 2); “The "Detailed Description of the Invention" again discloses that same diagnostic embodiment and further states that the method may optionally include the further step of treating the periodontal disease in the patient” (pg. 9, par. 3);
The arguments are not persuasive because they fail to overcome the rejection “the specification fails to disclose specific values, ranges, or parameters for calculations of the conditions for initiating the recited treatments” (OA, pg. 4, par. 2) - Applicant argues other aspects of the disclosure, which were not rejected.
Applicant argues that “The Office Action's position as to claim 24 is also misplaced. Claim 24 is a detection claim” (pg. 9, last par.) and “The Examiner's assertion that threshold values are required to determine whether the proteins are "present or absent" is not commensurate with the claim language. Claim 24 does not require any disease-significance cutoff It is directed to reagent-based detection of presence in a saliva sample” (pg. 10, par. 1). The argument is persuasive; therefore, the rejection of claim 24 under 112(a) is withdrawn.
Applicant argues that “The treatment-related limitations of claims 1, 11, 22, 23, and 26-31 are also expressly supported” and “The question is whether the inventors possessed the claimed subject matter, not whether the application exhaustively enumerates every downstream clinical judgment that may follow from the claimed assessment” (pg. 10, par. 2). The argument is persuasive; therefore, the paragraph stating “the specification fails to disclose any information on how to use the measured biomarker concentrations to choose appropriated treatment options among scaling, root planing, surgical pocket reduction, flap surgery, a gum graft, or a bone graft” (OA, pg. 5, par. 3) is removed from the rejection.
Applicant argues that “Dependent claims 2 and 5 are likewise supported on their own terms. The specification expressly discloses generating one, two, or three testing values corresponding to probabilities of periodontitis versus health/gingivitis, gingivitis versus health, and advanced periodontitis versus mild periodontitis” and “the "Detailed Description of the Invention" states that the subject's age may optionally be included as an additional marker and explains that a score between zero and one may be calculated using a linear or non-linear combination, including a sigmoid-function framework” (pg. 10, last par.).
The argument is not persuasive because the specification fails to disclose how one, two, or three testing values corresponding to probabilities are generated, which formulas or algorithms are used in the process. The arguments of the framework and the phrase “may be” have already been addressed above.
Applicant argues that “the specification expressly states that the four proteins are known in the art and that the skilled person is aware of their structures and methods for detecting them in an aqueous sample such as saliva. The application then provides the specific biomarker combinations and the classification frameworks discussed above. In these circumstances, the Examiner's demand for still more detail as to every possible numerical threshold or parameter exceeds what§ l 12(a) requires for written description” (pg. 11, par. 1).
The argument is not persuasive because the fact that the skilled person may be aware “of their structures and methods for detecting them in an aqueous sample such as saliva” does not substitute the lack of disclosure of the real evidence indicating the possession of the claimed invention, namely “the specification fails to disclose specific values, ranges, or parameters for calculations of the conditions for initiating the recited treatments” (OA, pg. 4, par. 2).
Applicant argues that “the Office bears the initial burden of adequately explaining why a person of ordinary skill would not recognize the disclosure as describing the claimed invention. Respectfully, the present rejection does not do so. The Office identifies the absence of particular numerical values, but does not meaningfully address the extensive disclosures that are present in the "Summary of the Invention," the "Detailed Description of the Invention," Fig. 3, the "Example," and Table 1. Those disclosures, taken together, reasonably convey possession of the inventions now claimed” (pg. 11, par. 2).
This argument is a wrong interpretation of the rejection and therefore, not persuasive. The Office does not have to “meaningfully address the extensive disclosures that are present in the "Summary of the Invention," the "Detailed Description of the Invention," Fig. 3, the "Example," and Table 1”. The rejection under 112(a) indicates what is missing in the disclosure. The Office takes disclosure of specific values, ranges, or parameters for calculations as a necessary condition of providing evidence for possession of the claimed invention, the invention that the claimed biomarkers can indeed be used for determining the testing value which is indicative for one or more of gingivitis, mild periodontitis, and advanced periodontitis. Disclosures of other aspects of the invention are necessary, but not sufficient. Disclosures of specific values, ranges, or parameters for calculations are required because they would be determined in the course of experimental method development, which is the only way to provide evidence of possession for a biomarker invention.
Subject Matter Free of the Prior Art
Claims 1, 2, 5, 11, 22-24, and 26-31 are free of the prior art.
The prior art references fail to teach 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, wherein the method comprises using specific combinations of proteins: either A1AGP, PK, and MMP-9; or A1AGP, PK, and S100A8.
The closest prior art:
Braun (PGPub 2010/0196941) teaches an in vitro method of detecting concentrations of a biomarker of periodontal disease MMP-9 ([0056]), but fails to teach the combinations of proteins consisting of A1AGP, PK, and MMP-9; or A1AGP, PK, and S100A8.
Chapple et al. (IDS; PGPub 2015/0219665) teaches three proteins A1AGP, PK, and MMP-9 among large number of other biomarkers of gingivitis and periodontitis, but fails to teach the combinations of proteins consisting of A1AGP, PK, and MMP-9; or A1AGP, PK, and S100A8.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
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 date of this final action.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677
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