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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 12, 2025 has been entered.
Status of Claims
Claims 1, 2, 5, 11, 22-24, and 26-32 were pending. Claims 1 and 22-24 are amended.
Claims 1, 2, 5, 11, 22-24, and 26-32 are examined.
Withdrawn Rejections
The rejection of claims 1, 2, 5, 11, 22-24, and 26-32 under 35 U.S.C. §103 is withdrawn in view of claims 1 and 22-24 amendments.
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, 22-24, 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 t1 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 the recited 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 ti 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.
Additionally, 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.
Regarding claim 24, the specification fails to disclose the threshold values for the recited biomarker proteins that are required to determine whether the proteins are present or absent in the sample. The biomarker proteins are naturally present in the human body; therefore, one can naturally expect some background level of these proteins detected even in the absence of gingivitis, mild periodontitis, or advanced periodontitis in the patient.
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.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS. —Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 32 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 32 recites “the method of claim 24, wherein the administered treatment comprises…”. Claim 24 does not recite any treatment.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant's arguments filed December 12, 2025 have been fully considered.
Applicant amends independent claims 1 and 22-24 to recite “proteins consisting of” and argues that “Chapple teaches a vast number of protein biomarkers with potentially over 2 million possible combinations thereof, and fails to teach or suggest the specific combination of biomarkers, as claimed” (pg. 7, last par.) and “Braun states, "In various embodiments of the methods, the two or more biomarkers include the combinations of biomarkers: .... ", which phrase is followed by about 9 full pages of patent text (pages 2-11 of Braun), with at least thousands of combinations of biomarkers, and none of them teaching the combination of biomarkers, as claimed” (pg. 8, par. 2). The argument is persuasive and the rejections under §103 are withdrawn.
Subject Matter Free of the Prior Art
Claims 1, 2, 5, 11, 22-24, and 26-32 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).
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
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677