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 .
Priority
The present application was filed on 10/05/2020. This application is a 371 of PCT/EP2019/058213 04/02/2019, which claims benefit of EUROPEAN PATENT OFFICE (EPO) 18166935.9 04/12/2018.
Claim status
Claims 3, 5-6, 10-19, 21-23, and 25 are canceled. Claims 1, 8, 9, 20, 24, and 26 have been amended. Claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 are pending.
Objections/Rejections status
The objection of claims 1 and 8 is withdrawn in view of the amendment of the claims.
The rejection of claims 1-2, 4, 7-9, 20, and 22-27 under 35 USC 112(b) is withdrawn in view of Applicant’s arguments filed on 01/14/26.
The rejection of claims 1-2, 4, 7-9, 20, and 22-27 under 35 USC 101 is withdrawn in view of the amendment of the claims.
The rejection of claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 under 35 USC 103 is updated in view of the amendment of the claims.
The rejection of claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 on the ground of nonstatutory double patenting as being unpatentable over the copending Application No. 17/046,473 and 17/046,430 are withdrawn because the two applications are abandoned.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 4, 7, and 24 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
The term “likely” in claim 1, line 18, is a relative term which renders the claim indefinite. The term “likely” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In particular, it is unclear how is “likely successfully respond to treatment of periodontal disease”. The treatment of periodontal disease is successful if the patient is recover from periodontal disease, but is not successful if the patient still has periodontal disease. The “likely successfully respond to treatment of periodontal disease” falls between the unsuccessful and the successful points. It is unclear where exactly the “likely successfully respond” is.
All dependent claims are also rejected based on their dependency of the defected parent claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 7-8, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Fiorellini et al. (US 20080027146) in view of Chapple et al (US 20150219665), Ebersole et al. (Targeted salivary biomarkers for discrimination of periodontal health and disease(s), Frontiers in cellular and infection microbiology 5 (2015): 62, PTO-892 dated 12/18/2023) and Buechler et al. (WO 2004059293).
Regarding claims 1, 7-8 and 20, Fiorellini teaches a method for “treating periodontal disease in a human patient based on assessing or predicting a response of the human patient to treatment of the periodontal disease” (see par.33-34 and par.91: Fiorellini teaches a method for monitoring the effectiveness of treatment of a subject having a periodontal disease).
The method comprises detecting, in a sample of saliva from said human patient suffering from periodontal disease, a concentration of protein markers (see par.29 and par.91: teaching that a sample is obtained from a subject at pre- and post-treatment time point, wherein the sample is a saliva sample, and a level of peptide marker expression in the sample is detected). In addition, Fiorellini discloses that the subject can be human (see par.54) and one or more markers can be used to diagnose periodontal disease (see par.8).
The method of Fiorellini also comprises administering, based on the assessed predicted successful treatment, a treatment for the periodontal disease in said patient (see par.91 page 11: teaching altering the administration of the agent to the subject according to the treatment evaluation). The treatment for periodontitis comprises therapeutic compounds or surgery (see par.5 and 58 teaching that antibacterial and antifungal agents are used for treating periodontitis, and par.124 teaching that conventional periodontal therapy includes oral hygiene instruction, scaling and root planing, surgical pocket reduction and regular periodontal maintenance care).
Fiorellini compares the level of expression or activity of the marker(s) in the pre-treatment sample with the marker(s) in the post-treatment sample (see par.91). Fiorellini discloses that marker expression or activity is used as an indicator of the effectiveness of a treatment (see par.91)). Fiorellini further teaches that a level of biomarker in the biological sample is detected and compared with the level of biomarker in a control sample, i.e., a threshold value (see par.12).
However, Fiorellini does not teach that the threshold value is based on a concentration determined for the proteins in one or more reference samples, each reference sample associated with successful treatment of periodontitis or unsuccessful treatment of periodontitis. Fiorellini does not teach the various groups of markers as claimed and determining at least one testing value reflecting the concentration determined for said proteins.
Buechler teaches methods for the identification and use of diagnostic markers for differential diagnosis of diseases and/or conditions (see Abstract). To identify subjects at risk for an underlying disease, i.e., periodontitis, the concentration of one or a plurality of biomarkers in a sample is compared to a threshold amount (see par.12-13). Buechler teaches that the advantage of using a panel of markers over a single marker is to increase the effectiveness of the test (see par.282, par.303). Buechler further teaches that the marker concentrations are linearly interpolated to a value between 0 and 1 (see par.284).
Examiner notes that the value between 0 to 1 taught by Buechler is the value reflecting the concentration determined for the test protein markers. Therefore, this teaching anticipates “determining a testing value reflecting the concentrations determined for said proteins” and the invention of claim 7.
In addition, Buechler teaches that a threshold for a single marker or a panel of markers can be set up to differentiate different disease states (i.e., normal or disease) (see par.274-275). Buechler also teaches that the threshold values can be determined based on the concentration of the marker values from the diseased and non-diseased subjects (see par. 273-285). Consequently, the threshold value is also based on the concentrations determined for the proteins in one or more reference samples; each sample is associated with the unsuccessful treatment (i.e., disease state) or successful treatment (i.e., normal state) as claimed.
Chapple teaches a method for diagnosing the status of periodontitis disease by analyzing and comparing the concentration of various proteins in gingival crevicular fluid and saliva samples amongst healthy and various diseased oral state individuals (see par.6, par.49-50). Chapple suggests the expression levels of one, two or more protein biomarkers define the status of an oral disease (see par.61). In particular, the set of protein biomarkers includes at least one protein selected from the group consisting of Alpha-1-acid glycoprotein and/or MMP-9 etc. (see par.12).
Chapple teaches that the levels of proteins of interest are shown relative to levels in a healthy control group (see supplemental table 1, par.95). The healthy control group can be considered as a successful treatment group because it shows <10% sites with G.I. of 1.0 or B.O.P. & no sites with G.I. of 2.0 or 3.0 (see Table 1). This definition corresponds to the definition in the Specification par.134-135.
Ebersole describes a saliva-based diagnostic approach for periodontal health and disease based upon the abundance of salivary analytes associated with disease (see Abstract). The method comprises detecting, in a sample of saliva from said human patient (see Abstract and page 3 paragraph 4), the concentrations of IL-1β, IL-6, MMP-8, MIP-1α (see Abstract). Ebersole concludes that the concentrations of IL-1β, IL-6, MMP-8, MIP-1α alone and in combination are able to distinguish a healthy subject from a subject with gingivitis and periodontitis (see abstract).
The change in concentration of proteins alpha-1-acid glycoprotein (A1AGP) and MMP-9 taught by Chapple (see par.12) and MMP-8 and IL-1beta taught by Ebersole (see Abstract) are associated with the status of periodontitis. While Chapple and Ebersole do not specifically teach the claimed groups of protein markers, Chapple suggests the expression levels of one, two or more protein biomarkers define a status of an oral disease (see par.61). Chapple and Ebersole give many examples of single or multiple proteins used as biomarkers to differentiate periodontitis. Buechler, in addition, teaches the advantage of using a panel of markers over a single marker to increase the effectiveness of the test (see par.282, and par.303).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Fiorellini, using the threshold values collected from sample associated with successful treatment (e.g., normal subject) or unsuccessful treatment (e.g., disease subject) as taught by Chapple and Buechler because these methods are functional equivalents to analyze an outcome of the treatment (i.e., the disease condition of a subject).
Moreover, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Fiorellini, using the analysis method taught by Buechler to determine a testing value reflecting the concentrations determined for said proteins and assess a human patient with or without periodontitis based on the response value of a panel biomarkers because Buechler’s analysis method is generic for differential disease conditions (see Buechler: Abstract). A person of ordinary skill in the art would have been motivated to combine these teachings because the probability of determining a subject with a disease state is defined rapidly and accurately (see at least in Buechler par.35, par.89).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Fiorellini, using the protein markers associated with periodontal disease taught by Chapple and Ebersole to create a panel of biomarkers for treating periodontal disease because the change in concentration of one or more proteins is helped to define a subject with periodontitis disease from a healthy subject (Chapple par.49, Ebersole: Abstract). The group of biomarkers encompasses the claimed group (i) A1AGP, IL-1beta, MMP-8 and MMP-9 and (ii) A1AGP, IL-1beta and at least one of MMP-8 or MMP-9. One having an ordinary skill in the art would have been motivated to use a panel of markers over a single marker because the panel of markers can increase the effectiveness of the test (Buechler see par.282, and par.303).
One having ordinary skill in the art would have had a reasonable expectation of success in combining these art references because Fiorellini teaches a method for monitoring the effectiveness of treatment of a subject having a disease by measuring the levels of biomarker’s expression, while Buechler’s analysis method comprises the comparison of the levels of one or a plurality test markers to the corresponding threshold can help (see Buechler par.12-13). Fiorellini, Chapple and Ebersole are directed to the use of biomarkers (i.e., protein) in saliva sample to diagnose and evaluate the periodontitis treatment (Fiorellini par.29, par.91; Chapple par.1; Ebersole Abstract).
As discussed above, Fiorellini, Chapple, Ebersole and Buechler disclose each and every element in the claimed method, the combined teaching is capable of performing the intended use of the claimed method, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Moreover, as the protein markers taught by Chapple, Ebersole are associated with the periodontitis, the detection of these markers help to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely successfully respond to treatment of periodontal disease because the subject has periodontitis.
Regarding claim 2, Fiorellini, Chapple, Ebersole, and Buechler teach the invention as discussed above. Fiorellini does not explicitly teach that the treatment was administered no more than 7, 6, 5, 4, 3, 2, or 1 day(s) prior to assessment. However, Fiorellini discloses that one sample from a subject is collected before treating and one or more samples from a subject are collected after treating (see par.91). Based on the changing level of expression of the marker in the samples at two time points, Fiorellini would alter the administration of the treatment to the subject accordingly (see par.91).
Examiner notes that Fiorellini is generic regarding when to collect the second sample as long as the concentration of the marker can be detected and compared between two collection time points (see par.11). It is the designer's choice to define when the second sample is collected to satisfy Fiorellini’s teaching. As a result, one having an ordinary skill in the art is able to evaluate the effectiveness of the treatment with a reasonable expectation of success.
Moreover, the combined method taught by Fiorellini, Chapple, Ebersole and Buechler comprises all the essential steps in the instant claimed method as discussed regarding claim 1. Therefore, the combined method taught by Fiorellini, Chapple, Ebersole and Buechler is able to predict the response of a human patient to a treatment for periodontitis, optionally wherein the treatment is proposed or was administered no more than 7, 6, 5, 4, 3, 2, or 1 day(s) prior to assessment as claimed.
Claims 4 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Fiorellini in view of Chapple, Ebersole and Buechler, as applied in claims 1 and 8 above, further in view of Murr et al. (Cross-Sectional Association of Salivary Proteins with Age, Sex, BodyMass Index, Smoking, and Education; J. Proteome Res. 2017, 16, 2273−2281, PTO-892 dated 12/18/2023).
Regarding claims 4 and 9, Fiorellini, Chapple, Ebersole, and Buechler teach the invention as discussed above.
The modified Fiorellini teach the threshold value limitation of claim 4. See the discussion of Chapple, Buechler and Ebersole above.
For the claimed proteins which consist of A1AGP, IL-1beta, MMP-9, and K-4 or MMP-8, the modified Fiorellini encompasses the claimed proteins because it consists of A1AGP, IL-1beta, and MMP-8. See the discussion of Chapple, Buechler and Ebersole in claim 1 above.
Regarding the combination of the age of the patient into the panel of testing markers recited in claims 4 and 9, Fiorellini does not teach that the age of the subject is determined and that the testing value reflects the joint concentrations determined for said proteins in combination with the age of the subject.
Buechler teaches that age, gender, race, etc. can be incorporated into the analysis panel (see par.[0083, 0375]).
Murr investigates the associations between common phenotypes (i.e., age) and salivary protein abundance (see page 2274 left col par.2). The phenotypes include age, sex, BMI, smoking and education (see page 2274 left col par.4). Murr confirms the influence of these common phenotypes, e.g., age on the salivary protein pattern of human subjects. In particular, age had a distinct influence on the salivary protein composition (see Abstract).
Therefore, it would have been obvious to one of ordinary skills in the art before the effective filing date of the claimed invention to modify the method taught by Fiorellini in view of Chapple, Buechler and Ebersole, incorporating the age of the study subjects in the analysis for defining periodontitis status because Murr demonstrates that the salivary protein abundance is age-related, thus the age should be considered when studying disease-related proteome signatures in saliva, i.e. periodontal disease (see Murr: Abstract). By doing so, the accuracy of Fiorellini’s method is improved, since the effect of covariables is minimized (see Murr page 2279 left col par.5). One having ordinary skill in the art would have had a reasonable expectation of success in combining Fiorellini and Murr because Buechler teaches that age can be one of the biomarkers in the analysis panel (see Buechler par.83, par.375).
Claims 24, 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Fiorellini in view of Chapple, Ebersole and Buechler, as applied in claims 1, 8 and 22 above, further in view of Khademi et al. (Stability of antibacterial activity of Chlorhexidine and Doxycycline in bovine root dentine, Journal of Research in Pharmacy Practice/Jan-Mar 2014/Vol 3/Issue 1, PTO-892 dated 05/09/2024).
Regarding claims 24, 26 and 27, Fiorellini, Chapple, Ebersole, and Buechler teach the invention as discussed above. Fiorellini does not teach the therapeutic agent being chlorhexidine and doxycycline.
Khademi teaches a method to reduce the microbial load in the root canal comprising chlorhexidine and doxycycline. Khademi shows that chlorhexidine and doxycycline are long-lasting antibacterial agents for treating periodontitis (see page 19 left col par.1, page 21 right col par.2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement chlorhexidine and doxycycline into the therapeutic agent in Fiorellini’s method, because Khademi teaches that it is necessary to use antibacterial agents to prevent the reinfection of root canal irrigation (see page 20 left col par.1). One having an ordinary skill in the art would have been motivated to use chlorhexidine and doxycycline with a reasonable expectation of success because Khademi teaches these drugs are long-lasting antibacterial agents for treating periodontitis.
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, 2, 4, 7, 8, 9, 20, 24, 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5 and 26-28 of copending Application No. 16/962,246 (‘246) in view of Ebersole et al. (Targeted salivary biomarkers for discrimination of periodontal health and disease(s), Frontiers in cellular and infection microbiology 5 (2015): 62) and Fiorellini et al. (PGPub 20080027146, PTO-892, 05/09/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 8 and 20, claims 1 and 2 of ‘246 encompass most the limitations of the instant claims. The method comprises detecting, in a sample of saliva from said human patient, the concentrations of the proteins A1AGP and MMP-9. Claim 2 of ‘246 recites “the threshold value is based on the concentrations of the proteins in a set of samples, including samples from subjects with healthy gum…”. Examiner interprets that subjects with healthy gum encompasses the subject with successful treatment of periodontal disease. Therefore claim 2 of ‘246 encompasses the comparing step in claim 1, 8 and 20.
However, claim 1 of ‘246 fail to teach the proteins further comprise IL-1beta; or further comprise IL-1beta and MMP-8 to fulfil the claimed proteins in group (i) or (ii) of the instant claims.
Ebersole describes a saliva-based diagnostic approach for periodontal health and disease based upon the abundance of salivary analytes associated with disease (see Abstract). The method comprises detecting, in a sample of saliva from said human patient (see Abstract and page 3 paragraph 4), the concentrations of IL-1β, IL-6, MMP-8, MIP-1α (see Abstract). Ebersole concludes the concentrations of IL-1β, IL-6, MMP-8, MIP-1α alone and in combination are able to distinguish healthy from gingivitis and periodontitis (see abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by ‘246, detecting proteins A1AGP, MMP-9, Il-1beta and MMP-8 as taught by ‘246 and Ebersole, to treat the patient or evaluate the efficacy of treating agent and monitor the disease outcome. One having ordinary skills in the art would have had a reasonable expectation of success in combining ‘246 and Ebersole because they use multiple saliva proteins as biomarkers for diagnosing periodontitis and evaluating the effectiveness of treatment.
As discussed above, the copending application and Ebersole disclose each and every element in the claimed method, the combined teaching is capable of performing the intended use of the claimed method, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Moreover, as the protein markers taught by the copending application and Ebersole are associated with the periodontitis, the detection of these markers help to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely successfully respond to treatment of periodontal disease because the subject has periodontitis.
Regarding claim 2, claim 5 of ‘246 teaches the patient is known to have periodontal disease, but fails to teach when to collect one or more samples.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. In addition, Fiorellini discloses the method for monitoring the effectiveness of treatment of a subject which has periodontitis (see par.33-34 and 91). Fiorellini discloses that one sample from a subject is collected before treating and one or more samples from a subject are collected after treating (see par.91). Based on the changing level of expression of the marker in the samples at two time points, Fiorellini would alter the administration of the treatment to the subject accordingly (see par.91).
Examiner notes that Fiorellini is generic regarding when to collect the second sample as long as the concentration of the marker can be detected and compared between two collection time points (see par.11). It is the designer's choice to define when the second sample is collected to satisfy the Fiorellini’s teaching. As a result, one having an ordinary skill in the art is able to evaluate the effectiveness of the treatment with a reasonable expectation of success.
Moreover, the combined method taught by ‘246 and Fiorellini is able to predict the response of a human patient to a treatment for periodontitis, optionally wherein the treatment is proposed or was administered no more than 7, 6, 5, 4, 3, 2, or 1 days prior to assessment as claimed.
Regarding claims 4, 7 and 9 about combining the age of the subject into analysis and determining the threshold value, claim 5 of ‘246 encompasses the limitation of the instant claims.
Regarding claims 24, 26-27, claims 26-28 of ‘246 encompasses the limitation of the instant claim.
Claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 7-8 and 10 of copending Application No. 17046361 (‘361) in view of Ebersole et al. (Targeted salivary biomarkers for discrimination of periodontal health and disease(s), Frontiers in cellular and infection microbiology 5 (2015): 62), Fiorellini et al. (PGPub 20080027146, PTO-892, 05/09/2024) and Khademi et al. (Stability of antibacterial activity of Chlorhexidine and Doxycycline in bovine root dentine, Journal of Research in Pharmacy Practice/Jan-Mar 2014/Vol 3/Issue 1, PTO-892, 05/09/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 8 and 20, claim 1 of ‘361 encompass most the limitations of the instant claims. The method comprises detecting, in a sample of saliva from said human patient, the concentrations of the proteins A1AGP, K-4 and MMP-8.
Claim 1 of ‘361 fails to teach that the concentration of proteins further comprises Il-1beta.
See discussion of Ebersole in the rejection for claim 1 above, the details of which have a similar application here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by ‘361, detecting proteins A1AGP, Il-1beta, K-4 and MMP-8 as taught by ‘473 and Ebersole, to treat the patient or evaluate the efficacy of treating agent and monitor the disease outcome. One having ordinary skills in the art would have had a reasonable expectation of success in combining ‘361 and Ebersole because they use multiple saliva proteins as biomarkers for diagnosing periodontitis and evaluating the effectiveness of treatment.
As discussed above, the copending application and Ebersole disclose each and every element in the claimed method, the combined teaching is capable of performing the intended use of the claimed method, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Moreover, as the protein markers taught by the copending application and Ebersole are associated with the periodontitis, the detection of these markers help to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely successfully respond to treatment of periodontal disease because the subject has periodontitis.
Regarding claim 2, claim 4 of ‘361 encompasses the limitation of the instant claim.
Regarding claims 4 and 9 about combining the age of the subject into analysis and determining the threshold value, claim 7-8 of ‘361 encompasses the limitation of the instant claim.
Regarding claim 7 about the concentration values is between 0-1, claim 10 of ‘361 encompasses the limitation of the instant claim.
Regarding claim 22-27, ‘361 fails to teach the specific treatment for periodontitis. See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. Also, Fiorellini discloses the treatment for periodontitis comprising therapeutic agent (see par.5, teaching antibiotic, see par.51), and dental procedure (see par.124, teaching the procedure comprising scaling and root planning, surgical pocket reduction).
Khademi teaches a method to reduce the microbial load in the root canal comprising chlorhexidine and doxycycline. Khademi shows that chlorhexidine and doxycycline are long-lasting antibacterial agents for treating periodontitis (see page 19 left col par.1, page 21 right col par.2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the treatment of Fiorellini and the method of ‘361 because ‘361 is generic to the treatment. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement chlorhexidine and doxycycline to the therapeutic agent in Fiorellini’s method because Khademi teaches that it is necessary to use antibacterial agents to prevent the reinfection of root canal irrigation (see page 20 left col par.1). The motivation to do so comes from chlorhexidine and doxycycline’s long-lasting activity as discussed above.
Claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 8 of copending Application No. 17045605 (‘605) in view of Fiorellini et al. (PGPub 20080027146) and Khademi et al. (Stability of antibacterial activity of Chlorhexidine and Doxycycline in bovine root dentine, Journal of Research in Pharmacy Practice/Jan-Mar 2014/Vol 3/Issue 1, PTO-892, 05/09/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 8, and 20, claims 1, 4-5 of ‘605 teaches a method for assessing if a human patient has oral disease comprising: detecting, in a sample of saliva from said human patient, the concentrations of the proteins A1AGP, IL-1beta, MMP-9, and MMP-8; determining a testing value reflecting the joint concentrations determined for said proteins; comparing said testing value with a threshold value reflecting in the same manner the joint concentrations associated with periodontitis, so as to assess whether the testing value is indicative for periodontitis in said patient.
Claim 1 of ‘605 does not teach treating the patient with periodontitis.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by ‘605, treating the patient as taught by Fiorellini to evaluate the efficacy of treating agent and monitor the disease outcome. One having ordinary skills in the art would have had a reasonable expectation of success in combining ‘605 and Fiorellini because they use multiple saliva proteins as biomarkers for diagnosing periodontitis.
As discussed above, the copending application and Fiorellini disclose each and every element in the claimed method, the combined teaching is capable of performing the intended use of the claimed method, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Moreover, as the protein markers taught by the copending application are associated with the periodontitis, the detection of these markers help to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely successfully respond to treatment of periodontal disease because the subject has periodontitis.
Regarding claim 2, claim 2 of ‘605 teaches the patient is suspect to have periodontal disease, but fails to teach when to collect one or more samples.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. In addition, Fiorellini discloses the method for monitoring the effectiveness of treatment of a subject which has periodontitis (see par.33-34 and 91). Fiorellini discloses that one sample from a subject is collected before treating and one or more samples from a subject are collected after treating (see par.91). Based on the changing level of expression of the marker in the samples at two time points, Fiorellini would alter the administration of the treatment to the subject accordingly (see par.91).
Examiner notes that Fiorellini is generic regarding when to collect the second sample as long as the concentration of the marker can be detected and compared between two collection time points (see par.11). It is the designer's choice to define when the second sample is collected to satisfy the Fiorellini’s teaching. As a result, one having an ordinary skill in the art is able to evaluate the effectiveness of the treatment with a reasonable expectation of success.
Moreover, the combined method taught by ‘605 and Fiorellini is able to predict the response of a human patient to a treatment for periodontitis, optionally wherein the treatment is proposed or was administered no more than 7, 6, 5, 4, 3, 2, or 1 days prior to assessment as claimed.
Regarding claims 4 and 9 about combining the age of the subject into analysis and determining the threshold value, claim 3-4 of ‘605 encompasses the limitation of the instant claim.
Regarding claim 7 about the concentration values is between 0-1, claim 8 of ‘605 encompasses the limitation of the instant claim.
Regarding claim 24, 26-27, claim 1 of ‘605 discloses that patient with periodontitis is treated with a therapeutic agent or a dental procedure, but fails to teach the specific treatment for periodontitis.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. Also, Fiorellini discloses the treatment for periodontitis comprising therapeutic agent (see par.5, teaching antibiotic, see par.51), and dental procedure (see par.124, teaching the procedure comprising scaling and root planning, surgical pocket reduction).
Khademi teaches a method to reduce the microbial load in the root canal comprising chlorhexidine and doxycycline. Khademi shows that chlorhexidine and doxycycline are long-lasting antibacterial agents for treating periodontitis (see page 19 left col par.1, page 21 right col par.2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the treatment of Fiorellini and the method of ‘605 because ‘361 is generic to the treatment. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement chlorhexidine and doxycycline to the therapeutic agent in Fiorellini’s method because Khademi teaches that it is necessary to use antibacterial agents to prevent the reinfection of root canal irrigation (see page 20 left col par.1). The motivation to do so comes from chlorhexidine and doxycycline’s long-lasting activity as discussed above.
Claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 and 7 of copending Application No. 17045312 (‘312) in view of Fiorellini et al. (PGPub 20080027146), Chapple et al (PGPub 20150219665), and Khademi et al. (Stability of antibacterial activity of Chlorhexidine and Doxycycline in bovine root dentine, Journal of Research in Pharmacy Practice/Jan-Mar 2014/Vol 3/Issue 1, PTO-892, 05/09/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 8, and 20, claim 1 of ‘312 teaches a method for assessing if a human patient has oral disease comprising: detecting, in a sample of saliva from said human patient, the concentrations of the proteins S100A9; determining a testing value reflecting the joint concentrations determined for said proteins; comparing said testing value with a threshold value reflecting in the same manner the joint concentrations associated with periodontitis, so as to assess whether the testing value is indicative for periodontitis in said patient.
Claim 1 of ‘312 does not teach treating the patient with periodontitis and fails to teach the concentration of protein MMP-9 to fulfil the claimed group (iii).
See discussion of Fiorellini and Chapple in the rejection for claim 1 above, the details of which have a similar application here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the method taught by ‘312 and Fiorellini, treating the patient or evaluating the efficacy of treating agent and monitor the disease outcome as taught by Fiorellini. One having ordinary skills in the art would have had a reasonable expectation of success in combining ‘312 and Fiorellini because they use multiple saliva proteins as biomarkers for diagnosing periodontitis.
As discussed above, the copending application and Fiorellini disclose each and every element in the claimed method, the combined teaching is capable of performing the intended use of the claimed method, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Moreover, as the protein markers taught by the copending application are associated with the periodontitis, the detection of these markers help to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely successfully respond to treatment of periodontal disease because the subject has periodontitis.
Regarding claim 2, ‘312 fails to teach the patient have periodontal disease, and when to collect one or more samples.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. In addition, Fiorellini discloses the method for monitoring the effectiveness of treatment of a subject which has periodontitis (see par.33-34 and 91). Fiorellini discloses that one sample from a subject is collected before treating and one or more samples from a subject are collected after treating (see par.91). Based on the changing level of expression of the marker in the samples at two time points, Fiorellini would alter the administration of the treatment to the subject accordingly (see par.91).
Examiner notes that Fiorellini is generic regarding when to collect the second sample as long as the concentration of the marker can be detected and compared between two collection time points (see par.11). It is the designer's choice to define when the second sample is collected to satisfy the Fiorellini’s teaching. As a result, one having an ordinary skill in the art is able to evaluate the effectiveness of the treatment with a reasonable expectation of success.
Moreover, the combined method taught by ‘605 and Fiorellini is able to predict the response of a human patient to a treatment for periodontitis, optionally wherein the treatment is proposed or was administered no more than 7, 6, 5, 4, 3, 2, or 1 days prior to assessment as claimed.
Regarding claims 4 and 9 about combining the age of the subject into analysis and determining the threshold value, claim 2 of ‘312 encompasses the limitation of the instant claim.
Regarding claim 7 about the concentration values is between 0-1, claim 7 of ‘312 encompasses the limitation of the instant claim.
Regarding claim 24 and 26-27, claim 1 of ‘312 discloses that patient with periodontitis is treated with a therapeutic agent or a dental procedure, but fails to teach the specific treatment for periodontitis.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. Also, Fiorellini discloses the treatment for periodontitis comprising therapeutic agent (see par.5, teaching antibiotic, see par.51), and dental procedure (see par.124, teaching the procedure comprising scaling and root planning, surgical pocket reduction).
Khademi teaches a method to reduce the microbial load in the root canal comprising chlorhexidine and doxycycline. Khademi shows that chlorhexidine and doxycycline are long-lasting antibacterial agents for treating periodontitis (see page 19 left col par.1, page 21 right col par.2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the treatment of Fiorellini and the method of ‘312 because ‘312 is generic to the treatment. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement chlorhexidine and doxycycline to the therapeutic agent in Fiorellini’s method because Khademi teaches that it is necessary to use antibacterial agents to prevent the reinfection of root canal irrigation (see page 20 left col par.1). The motivation to do so comes from chlorhexidine and doxycycline’s long-lasting activity as discussed above.
Claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 12,050,233 in view of Chapple et al (PGPub 20150219665), Fiorellini et al. (PGPub 20080027146), and Khademi et al. (Stability of antibacterial activity of Chlorhexidine and Doxycycline in bovine root dentine, Journal of Research in Pharmacy Practice/Jan-Mar 2014/Vol 3/Issue 1, PTO-892, 05/09/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 8 and 20, claim 1 of ‘233 teaches a method for treating a human patient having periodontitis comprising: detecting, in a sample of saliva from said human patient, the concentrations of the proteins Il-1beta and MMP-9; determining a testing value reflecting the joint concentrations determined for said proteins; comparing said testing value with a threshold value reflecting in the same manner the joint concentrations associated with periodontitis, so as to assess whether the testing value is indicative for periodontitis in said patient.
Claim 1 of ‘233 fails to teach the concentration of protein A1AGP to fulfil the claimed group (ii).
See discussion of Chapple in the rejection for claim 1 above, the details of which have a similar application here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by ‘233, detecting the concentration of proteins A1AGP, Il-1beta, and MMP-9 for treating the patient or evaluating the efficacy of treating agent and monitor the disease outcome as taught by ‘233 and Chapple. One having ordinary skills in the art would have had a reasonable expectation of success in combining ‘233 and Chapple because they use multiple saliva proteins as biomarkers for diagnosing periodontitis.
As discussed above, the copending application and Chapple disclose each and every element in the claimed method, the combined teaching is capable of performing the intended use of the claimed method, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Moreover, as the protein markers taught by the copending application and Chapple are associated with the periodontitis, the detection of these markers help to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely successfully respond to treatment of periodontal disease because the subject has periodontitis.
Regarding claim 2, claim 2 of ‘233 teaches the patient is known to have periodontal disease, but fails to teach when to collect one or more samples.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. In addition, Fiorellini discloses the method for monitoring the effectiveness of treatment of a subject which has periodontitis (see par.33-34 and 91). Fiorellini discloses that one sample from a subject is collected before treating and one or more samples from a subject are collected after treating (see par.91). Based on the changing level of expression of the marker in the samples at two time points, Fiorellini would alter the administration of the treatment to the subject accordingly (see par.91).
Examiner notes that Fiorellini is generic regarding when to collect the second sample as long as the concentration of the marker can be detected and compared between two collection time points (see par.11). It is the designer's choice to define when the second sample is collected to satisfy the Fiorellini’s teaching. As a result, one having an ordinary skill in the art is able to evaluate the effectiveness of the treatment with a reasonable expectation of success.
Moreover, the combined method taught by ‘233 and Fiorellini is able to predict the response of a human patient to a treatment for periodontitis, optionally wherein the treatment is proposed or was administered no more than 7, 6, 5, 4, 3, 2, or 1 days prior to assessment as claimed.
Regarding claims 4 and 9 about combining the age of the subject into analysis and determining the threshold value, claims 1 of ‘233 encompasses the limitation of the instant claim.
Regarding claim 7 about the concentration values is between 0-1, claim 1 of ‘233 encompasses the limitation of the instant claim.
Regarding claims 24 and 26-27, claim 1 of ‘233 discloses that patient with periodontitis is treated with a therapeutic agent or a dental procedure, but fails to teach the specific treatment for periodontitis.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. Also, Fiorellini discloses the treatment for periodontitis comprising therapeutic agent (see par.5, teaching antibiotic, see par.51), and dental procedure (see par.124, teaching the procedure comprising scaling and root planning, surgical pocket reduction).
Khademi teaches a method to reduce the microbial load in the root canal comprising chlorhexidine and doxycycline. Khademi shows that chlorhexidine and doxycycline are long-lasting antibacterial agents for treating periodontitis (see page 19 left col par.1, page 21 right col par.2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the treatment of Fiorellini and the method of ‘233 because ‘233 is generic to the treatment. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement chlorhexidine and doxycycline to the therapeutic agent in Fiorellini’s method because Khademi teaches that it is necessary to use antibacterial agents to prevent the reinfection of root canal irrigation (see page 20 left col par.1). The motivation to do so comes from chlorhexidine and doxycycline’s long-lasting activity as discussed above.
Claims 1, 2, 4, 7, 8, 9, 20, 24, 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4 and 8 of copending Application No. 17046397 (‘397) in view of Ebersole et al. (Targeted salivary biomarkers for discrimination of periodontal health and disease(s), Frontiers in cellular and infection microbiology 5 (2015): 62), Fiorellini et al. (PGPub 20080027146), and Khademi et al. (Stability of antibacterial activity of Chlorhexidine and Doxycycline in bovine root dentine, Journal of Research in Pharmacy Practice/Jan-Mar 2014/Vol 3/Issue 1, PTO-892, 05/09/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 8 and 20, claim 1 of ‘397 teaches a method for determining a human patient having gingivitis comprising: detecting, in a sample of saliva from said human patient, the concentrations of the proteins A1AGP and K-4; determining a testing value based on the detected join concentrations of the proteins; comparing the testing value with a threshold value of joint concentrations associated with gingivitis, determining that the human patient has gingivitis when the testing value exceeds the threshold value; 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 gingivitis. Claim 4 of ‘397 teaches “the threshold value is… associated with presence of gingivitis or absence of gingivitis.” The teaching in bold encompasses the threshold value associating with successful treatment of periodontal disease.
Claim 1 of ‘397 fails to teach the concentration of proteins further comprises MMP-8 and Il-1beta to fulfil the claimed group (ii).
See discussion of Ebersole in the rejection for claim 1 above, the details of which have a similar application here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by ‘397, detecting the concentration of proteins A1AGP and K-4 (as taught by ‘397) in combined with Il-1beta and MMP-8 (as taught by Ebersole) for treating the patient or evaluating the efficacy of treating agent and monitor the disease outcome. One having ordinary skills in the art would have had a reasonable expectation of success in combining ‘397 and Ebersole because they use multiple saliva proteins as biomarkers for diagnosing periodontitis.
As discussed above, the copending application and Ebersole disclose each and every element in the claimed method, the combined teaching is capable of performing the intended use of the claimed method, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Moreover, as the protein markers taught by the copending application and Ebersole are associated with the periodontitis, the detection of these markers help to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely successfully respond to treatment of periodontal disease because the subject has periodontitis.
Regarding claim 2, claim 2 of ‘397 teaches the patient is suspected to have periodontal disease, but fails to teach when to collect one or more samples.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. In addition, Fiorellini discloses the method for monitoring the effectiveness of treatment of a subject which has periodontitis (see par.33-34 and 91). Fiorellini discloses that one sample from a subject is collected before treating and one or more samples from a subject are collected after treating (see par.91). Based on the changing level of expression of the marker in the samples at two time points, Fiorellini would alter the administration of the treatment to the subject accordingly (see par.91).
Examiner notes that Fiorellini is generic regarding when to collect the second sample as long as the concentration of the marker can be detected and compared between two collection time points (see par.11). It is the designer's choice to define when the second sample is collected to satisfy the Fiorellini’s teaching. As a result, one having an ordinary skill in the art is able to evaluate the effectiveness of the treatment with a reasonable expectation of success.
Moreover, the combined method taught by ‘397 and Fiorellini is able to predict the response of a human patient to a treatment for periodontitis, optionally wherein the treatment is proposed or was administered no more than 7, 6, 5, 4, 3, 2, or 1 days prior to assessment as claimed.
Regarding claims 4 and 9 about combining the age of the subject into analysis and determining the threshold value, claims 3 of ‘397 encompasses the limitation of the instant claim.
Regarding claim 7 about the concentration values is between 0-1, claim 8 of ‘397 encompasses the limitation of the instant claim.
Regarding claims 24 and 26-27, claim 1 of ‘397 discloses that patient with periodontitis is treated with a therapeutic agent or a dental procedure, but fails to teach the specific treatment for periodontitis.
See discussion of Fiorellini in the rejection for claim 1 above, the details of which have a similar application here. Also, Fiorellini discloses the treatment for periodontitis comprising therapeutic agent (see par.5, and par.51), and dental procedure (see par.124, teaching the procedure comprising scaling and root planning, surgical pocket reduction).
Khademi teaches a method to reduce the microbial load in the root canal comprising chlorhexidine and doxycycline. Khademi shows that chlorhexidine and doxycycline are long-lasting antibacterial agents for treating periodontitis (see page 19 left col par.1, page 21 right col par.2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the treatment of Fiorellini and the method of ‘397 because ‘397 is generic to the treatment. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement chlorhexidine and doxycycline to the therapeutic agent in Fiorellini’s method because Khademi teaches that it is necessary to use antibacterial agents to prevent the reinfection of root canal irrigation (see page 20 left col par.1). The motivation to do so comes from chlorhexidine and doxycycline’s long-lasting activity as discussed above.
Response to Arguments
Applicant's arguments filed 01/14/2026 have been fully considered but they are not persuasive.
Independent claims 1, 8, and 20 have been amended to more clearly recite that the claimed method is directed toward, among other things, assessing that the patient will or will likely successfully respond to treatment of periodontal disease. Applicant argued that Fiorellini teaches determining from the before and after samples or from evaluation of treatment already administered, whether a treatment, already administered, has been successful or not. Fiorellini, taken alone or in combination with the other applied references, fail to teach an assessment that the patient will or will likely successfully respond to treatment, as claimed. Further Buechler teaches identifying subjects at risk for an underlying disease by comparing the concentration of one or more biomarkers in a sample with a threshold amount. Chapple teaches levels of proteins of interest relative to levels in healthy control group (supplemental table 1, par. 95), for diagnostic purposes and/ or to analyze the outcome of a treatment already administered. Buechler and Chapple, therefore, also fail to teach an assessment that a patient will or will likely successfully respond to treatment, as claimed.
These argument are not persuasive. In this case, Fiorellini teaches a method that comprises the main steps of the claimed method: detecting, in a sample of saliva from said human patient suffering from periodontal disease, a concentration of protein markers associated with periodontitis (see par.29 and par.91); comparing the level of expression or activity of the marker(s) in the pre-treatment sample with the marker(s) in the post-treatment sample (see par.91); comparing the level of expression or activity of the marker(s) with the level of biomarker in a control sample (see par.12); administering a treatment for the periodontal disease in said patient wherein the treatment for periodontitis comprises antibacterial and antifungal agents, antibacterial and antifungal agents etc. (see par.5, 58, 91 page 11 and par.124).
Chapple and Ebersole teach a plurality of proteins markers in saliva that are associated with periodontitis, such as A1AGP, MMP-9, IL-1β, and MMP-8 (see Chapple par.12, see Ebersole Abstract). Buechler teaches methods for the identification and use of diagnostic markers for differential diagnosis of diseases and/or conditions (see Abstract). Buechler teaches that the advantage of using a panel of markers over a single marker is to increase the effectiveness of the test (see par.282, par.303). Buechler and Chapple teach that to identify subjects at risk for an underlying disease, i.e., periodontitis, the concentration of one or a plurality of biomarkers in a sample is compared to a threshold amount (see Buechler par.12-13; see Chapple supplemental table 1, par.95), wherein the threshold values can be determined based on the concentration of the marker values from non-diseased subjects or healthy subjects (see Buechler par. 273-285, Chapple supplemental table 1, par.95).
The value from non-diseased subjects or healthy subjects can reflect in the same manner the value associated with successful treatment of a disease, e.g., periodontitis because the patients has been recovered from the disease after being treated and the patients become healthy again.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Fiorellini, Chapple, Ebersole and Buechler to arrive as the claimed method for monitoring the effectiveness of treatment of a subject having a periodontal disease with a reasonable expectation of success because the combined method and the use of biomarkers such as A1AGP, MMP-9, IL-1β, and MMP-8 improve the accuracy of the periodontitis diagnosis. See the discussion of Fiorellini, Chapple, Ebersole and Buechler in the office action above.
While the intended purpose of the combined method of Fiorellini, Chapple, Ebersole and Buechler is not the same as the intended purpose of the amended claimed invention, the combined method steps are all taught by the prior art and are obvious as written. Clearly, the method of the prior art may be used for the same purpose as those claimed, which is assessing that the patient will or will likely successfully respond to treatment of periodontal disease because the combined method discloses each and every element in the claimed method. Moreover, as the protein biomarkers taught by Chapple and Ebersole are associated with periodontitis, the detection of these markers helps to identify if a subject has periodontitis. Therefore, it is obvious that the subject will be likely to respond successfully to treatment of periodontal disease because the subject has periodontitis.
Furthermore, in the specification page 7 lines 22-34, Applicant discloses that the method predicts the response of a human patient to a treatment for periodontitis by assessing the concentration of the claimed biomarkers after the patient has been recently treated. Applicant states that this method is desired to know at an early stage whether the treatment is likely to be effective. This method is in line with the teaching of Fiorellini, which measures the concentration of the biomarkers associated with periodontitis in post-treatment samples to access the effectiveness of the treatment on the patient (see Fiorellini par.12 and 91). So it is obvious that the method of Fiorellini can predict the response of a human patient to a treatment for periodontitis because the methodology and analytical approach of Fiorellini and the claimed invention are identical.
Since the rejection of the claims under 35 U.S.C. § 103, claims 1-2, 4, 7-9, 20, and 22-27 are rendered obvious over the cited copending applications and/or issued patent in view of one or more of Fiorellini, Chapple, Khademi, and Ebersole. Accordingly, the rejections of the claims on the ground of nonstatutory double patenting are proper.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHAU N.B. TRAN whose telephone number is (571)272-3663. The examiner can normally be reached Mon-Fri 8:30-6:30 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L 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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/CHAU N.B. TRAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 17, 2026
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