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 .
The examiner reviewing this application in the USPTO have changed. All new correspondence should be directed to examiner Bailey Buchanan, Art Unit 1682.
Election/Restrictions
Applicant's election with traverse of the species election of the single combination of bacteria consisting of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in claims 1 & 19 in the reply filed on 06/12/2026 is acknowledged. The traversal is on the ground(s) that the pending claims share a single general inventive concept and a common special technical feature as the claims are commonly directed to determining the severity of periodontal bacteria by real time PCR or by 16S rRNA sequencing analysis and comparing a resulting bacterial % or bacterial count against reference values defined for a plurality of distinct clinical categories, namely normal individuals, patients with gingivitis, moderate periodontitis, and severe periodontitis which is confirmed by the instant specification. The traversal is also on the grounds that the reference relied upon by the examiner, Swamoto, fails to teach or suggest this common special technical feature and that Swamoto is directed to a binary comparison between subjects having periodontitis and healthy subjects and Swamoto fails to teach or suggest the recited determination that distinguishes among multiple clinical categories using defined cut-off criteria for the elected combination of bacteria and therefore the common technical feature makes a contribution over Swamoto and constitutes a special technical feature that links the claimed inventions such that unity of invention is present. This is not found persuasive because
The requirement is still deemed proper and is therefore made FINAL.
A first office action on the merits of claims 1, 3-9, 11-13, 15-17, & 19-23 with the species election of the single combination of bacteria consisting of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra is set forth herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pg. 23. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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, 3-9, 11-13, 15-17, & 19-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
It is noted that the claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
Regarding claim 1, the claim recites the limitation “the group” in line 9 of the claim and there is insufficient antecedent basis for this limitation in the claim.
Regarding claim 3, the recitation of “wherein the comparing comprises comparing the bacterial % or bacterial count” in lines 1-2 of the claim followed by the recitation of “a cut-off value set through the bacterial % and the bacterial count” in line 3 of the claim is unclear how the cut-off value is set through bacterial % and bacterial count when comparing comprises comparing bacterial % or bacterial count. In addition, the recitation of “ a cut-off value set through the bacterial % and the bacterial count according to severity of disease divided by a probing pocket, a degree of bleeding on probing, and a degree of alveolar bone resorption which indicate the severity of periodontitis” in lines 3-5 of the claim is unclear how these variables of probing pocket, degree of bleeding on probing, and degree of alveolar bone resorption determine a cut-off value and how that cut-off value is used to indicate severity of periodontitis.
Regarding claim 5, the recitations of “represented by” in lines 3-7 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-16], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs.
Regarding claim 6, the recitations of “represented by” in lines 1-9 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-16], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs.
Regarding claim 7, the recitation of “based on a cut-off value of the bacterial %” in lines 2-3 of the claim is unclear what the relationship is between bacterial % and a cut-off value or how the bacterial % is used to obtain a cut-off value. In addition, the recitations of “represented by” in lines 4, 5, & 7-9 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-10], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-9 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related.
Regarding claim 8, the recitation of “based on a cut-off value of the bacterial count” in lines 2-3 of the claim is unclear what the relationship is between bacterial count and a cut-off value or how the bacterial count is used to obtain a cut-off value. In addition, the recitations of “represented by” in lines 4-6 & 8-11 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-12, 15, & 16], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-11 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related.
Regarding claim 9, the claim is generally narrative and indefinite, failing to conform with current U.S. practice. It appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. In addition, the recitation of “wherein the cut-off value is derived from … which is defined by a subject whose probing pocket depth of individual teeth is less than or equal to 3 mm … and periodontitis which is accompanied by alveolar bone resorption” in lines 1-9 of the claim is unclear these variables of derive a cut-off value.
Regarding claim 11, the recitation of “based on a cut-off value of the bacterial %” in lines 2-3 of the claim is unclear what the relationship is between bacterial % and a cut-off value or how the bacterial % is used to obtain a cut-off value. In addition, the recitations of “represented by” in lines 4 & 5 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-4], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-5 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related.
Regarding claim 12, the recitation of “based on a cut-off value of the bacterial count” in lines 2-3 of the claim is unclear what the relationship is between bacterial count and a cut-off value or how the bacterial count is used to obtain a cut-off value. In addition, the recitations of “represented by” in lines 4-6 & 8-13 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-16], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-13 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related.
Regarding claim 13, the claim is generally narrative and indefinite, failing to conform with current U.S. practice. It appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. In addition, the recitation of “wherein the cut-off value is derived from … to distinguish gums with periodontitis accompanied by alveolar bone resorption from healthy gums and gums with gingivitis in a gum state not accompanied by alveolar bone resorption based on the bacterial % or bacterial count” in lines 1-5 of the claim is unclear these variables of derive a cut-off value.
Regarding claim 15, the recitation of “based on a cut-off value of the bacterial %” in lines 2-3 of the claim is unclear what the relationship is between bacterial % and a cut-off value or how the bacterial % is used to obtain a cut-off value. In addition, the recitations of “represented by” in lines 4-7 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-6], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 4-7 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related.
Regarding claim 16, the recitation of “based on a cut-off value of the bacterial count” in lines 2-3 of the claim is unclear what the relationship is between bacterial count and a cut-off value or how the bacterial count is used to obtain a cut-off value. In addition, the recitations of “represented by” in lines 4-9 of the claim is unclear. The term “represented by” is unclear because it is not clear if the term intends the claimed sequences to be limited to SEQ ID NO: 1 [and SEQ ID NOs: 2-6, 9, 10, 13, & 14], or if, for example it refers to a region of a target nucleic acid that acts as a substitute for another sequence within the same region, or if it allows for sequence changes from the recited SEQ ID NOs. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 4-9 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related.
Regarding claim 17, the claim is generally narrative and indefinite, failing to conform with current U.S. practice. It appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. In addition, the recitation of “wherein the cut-off value is derived from … wherein the severe periodontitis comprises periodontitis that show probing pockets … and has furcation-involved lesions caused by alveolar bone resorption in posterior teeth” in lines 1-9 of the claim is unclear these variables of derive a cut-off value.
Regarding claim 19, the claim recites the limitation “the group” in line 8 of the claim and there is insufficient antecedent basis for this limitation in the claim.
Regarding claim 20, the recitation of “wherein cut-off values are” in line 1 of the claim followed by the recitation of “and, if the bacterial % is greater than or equal to the corresponding cut-off value, healthy gums and periodontal diseases are distinguished” in lines 5-6 of the claim is unclear how the bacterial % is used to determine the cut-off values and how “if the bacterial % is greater than or equal to a corresponding cut-off value” distinguishes being healthy gums and periodontal diseases.
Regarding claim 21, the recitation of “wherein cut-off values are” in line 1 of the claim followed by the recitation of “and, if the bacterial % is greater than or equal to the corresponding cut-off value, healthy gum/gingivitis and periodontitis are distinguished” in lines 5-6 of the claim is unclear how the bacterial % is used to determine the cut-off values and how “if the bacterial % is greater than or equal to a corresponding cut-off value” distinguishes being healthy gums and periodontal diseases.
Regarding claim 22, the recitation of “wherein cut-off values are” in line 1 of the claim followed by the recitation of “and, if the bacterial % is greater than or equal to the corresponding cut-off value, healthy gum/gingivitis/moderate periodontitis and severe periodontitis are distinguished” in lines 4-6 of the claim is unclear how the bacterial % is used to determine the cut-off values and how “if the bacterial % is greater than or equal to a corresponding cut-off value” distinguishes being healthy gums and periodontal diseases.
Claim 4 is rejected due to its dependence on claim 1 and claim 23 is rejected due to its dependence on claim 19.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3-9, 11-13, 15-17, & 19-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method of providing information necessary for a diagnosis of a periodontal disease comprising performing quantitative analysis through real-time PCR with one or more bacteria and comparing bacterial % or bacterial count from normal individuals and patients with gingivitis, moderate periodontitis, and severe periodontitis wherein the comparing comprises comparing with a cut-off value which indicate the severity of the periodontitis. This recitation is a natural correlation between quantitative analysis with one or more bacteria and severity of periodontitis. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites “comparing a bacterial % or bacterial count obtained through the quantitative analysis by real-time PCR with that selected from the group consisting of normal individuals and patients with gingivitis, moderate periodontitis, and severe periodontitis” which is a recitation of an abstract idea because it encompasses conclusions and determinations which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of performing quantitative analysis by real-time PCR with one or more bacteria and comparing a bacterial % or bacterial count obtained through the quantitative analysis by real-time PCR, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the step of obtaining a sample is considered insignificant post solution activity. The steps of performing quantitative analysis by real-time PCR are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 4, 9, 13, 17, & 19-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Togawa (United States Patent Application Publication US 2021/0238659 A1, August 2021), in view of Tomás (Tomás et al.; Frontiers in Microbiology, Vol. 8, pages 1-16, August 2017), as cited in the IDS dated 04/11/2024.
Regarding claim 1, Togawa teaches an intraoral examination method for measuring a signal intensity of a nucleic acid from an oral bacterial group present in an oral sample comprising calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR (performing quantitative analysis real-time PCR with one or more bacteria), wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra (one or more bacteria selected from Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra), and determining a state of periodontal disease using the obtained calculated value as an index and comparing the obtained calculated value with a cut-off value of the abundance ratio of bacterial groups (comparing a bacterial % or bacterial count obtained through real-time PCR with that of patients with periodontitis) (paragraph [0039] lines 1-6; paragraph [0040] lines 1-5; paragraph [0041] lines 1-4; paragraph [0091] lines 1-5; paragraph [0098] lines 1-35).
Togawa does not teach that the comparison of the bacterial % or bacterial count with that of normal individuals and patients with periodontitis.
Tomás teaches a method for diagnosis of chronic (severe) periodontitis based on quantitative real-time PCR analysis of a group of bacterial species (one or more bacteria) comprising comparing the detection frequences and levels of the group of bacterial species (bacterial % or bacterial count obtained through quantitative real-time PCR) detected in subgingival sites with different periodontal conditions of a healthy control site (healthy individuals) and moderate to severe chronic (severe) periodontal site (patients with moderate or severe periodontitis) (abstract lines 1-32; pg. 2-3 paragraph bridging pg. 2 & 3 lines 1-18; pg. 4 column 2 1st full paragraph lines 1-15). Tomás also teaches that this method provides good predictive accuracy enabling improved patient monitoring and control of disease at the site-specific level (pg. 13-14 paragraph bridging pg. 13 & 14 lines 5-20).
Togawa and Tomás are considered to be analogous to the claimed invention because they are all in the same field of detection and quantification of bacterial species through real-time PCR in patients with periodontitis. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra and comparing the obtained calculated value with a cut-off value of the abundance ratio of bacterial groups in Togawa to incorporate comparing the detection frequences and levels of the group of bacterial species (bacterial % or bacterial count) with different periodontal conditions of a healthy control site (healthy individuals) and moderate to severe chronic (severe) periodontal site (patients with moderate or severe periodontitis) as taught in Tomás because Tomás teaches that doing so would provide a method with good predictive accuracy enabling improved patient monitoring and control of disease at the site-specific level.
Regarding claim 3, it is noted, as discussed above, the recitation of “wherein the comparing comprises comparing the bacterial % or bacterial count” in lines 1-2 of the claim followed by the recitation of “a cut-off value set through the bacterial % and the bacterial count” in line 3 of the claim is unclear how the cut-off value is set through bacterial % and bacterial count when comparing comprises comparing bacterial % or bacterial count. In addition, the recitation of “ a cut-off value set through the bacterial % and the bacterial count according to severity of disease divided by a probing pocket, a degree of bleeding on probing, and a degree of alveolar bone resorption which indicate the severity of periodontitis” in lines 3-5 of the claim is unclear how these variables of probing pocket, degree of bleeding on probing, and degree of alveolar bone resorption determine a cut-off value and how that cut-off value is used to indicate severity of periodontitis. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining a cut-off value with a bacterial % or bacterial count value while considering disease variables of probing pocket, a degree of bleeding on probing, and a degree of alveolar bone resorption.
Togawa teaches determining a state of periodontal disease using the obtained calculated value as an index and comparing the obtained calculated value with a cut-off value of the abundance ratio of bacterial groups (determining a cut-off value with bacterial % or bacterial count) (paragraph [0039] lines 1-6; paragraph [0040] lines 1-5; paragraph [0041] lines 1-4).
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) and further teaches assessing other clinical parameters comprising bleeding on probing, probing pocket depth, and clinical attachment loss (alveolar bone resorption) (determining a cut-off value with bacterial % or bacterial count while considering variables of probing pocket, a degree of bleeding on probing, and a degree of alveolar bone resorption) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Regarding claim 4, Togawa teaches the oral sample collected from a subject comprises a saliva sample (paragraph [0162] lines 1-5).
Regarding claim 9, it is noted, as discussed above, the claim is generally narrative and indefinite, failing to conform with current U.S. practice. It appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. In addition, the recitation of “wherein the cut-off value is derived from … which is defined by a subject whose probing pocket depth of individual teeth is less than or equal to 3 mm … and periodontitis which is accompanied by alveolar bone resorption” in lines 1-9 of the claim is unclear these variables of derive a cut-off value. Therefore, for the purposes of this rejection the claim is given its broadest reasonable interpretation to comprise determining a cut-off value by obtaining a ROC curve and selecting an ACU value of greater than or equal to 0.7.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) and further teaches assessing other clinical parameters comprising bleeding on probing, probing pocket depth, and clinical attachment loss (alveolar bone resorption) (determining a cut-off value with bacterial % or bacterial count while considering variables of probing pocket, a degree of bleeding on probing, and a degree of alveolar bone resorption) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Regarding claim 13, it is noted, as discussed above, the claim is generally narrative and indefinite, failing to conform with current U.S. practice. It appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. In addition, the recitation of “wherein the cut-off value is derived from … to distinguish gums with periodontitis accompanied by alveolar bone resorption from healthy gums and gums with gingivitis in a gum state not accompanied by alveolar bone resorption based on the bacterial % or bacterial count” in lines 1-5 of the claim is unclear these variables of derive a cut-off value. Therefore, for the purposes of this rejection the claim is given its broadest reasonable interpretation to comprise determining a cut-off value by obtaining a ROC curve and selecting an ACU value of greater than or equal to 0.7.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) and further teaches assessing other clinical parameters comprising bleeding on probing, probing pocket depth, and clinical attachment loss (alveolar bone resorption) (determining a cut-off value with bacterial % or bacterial count while considering variables of probing pocket, a degree of bleeding on probing, and a degree of alveolar bone resorption) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Regarding claim 17, it is noted, as discussed above, the claim is generally narrative and indefinite, failing to conform with current U.S. practice. It appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. In addition, the recitation of “wherein the cut-off value is derived from … wherein the severe periodontitis comprises periodontitis that show probing pockets … and has furcation-involved lesions caused by alveolar bone resorption in posterior teeth” in lines 1-9 of the claim is unclear these variables of derive a cut-off value. Therefore, for the purposes of this rejection the claim is given its broadest reasonable interpretation to comprise determining a cut-off value by obtaining a ROC curve and selecting an ACU value of greater than or equal to 0.7.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) and further teaches assessing other clinical parameters comprising bleeding on probing, probing pocket depth, and clinical attachment loss (alveolar bone resorption) (determining a cut-off value with bacterial % or bacterial count while considering variables of probing pocket, a degree of bleeding on probing, and a degree of alveolar bone resorption) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Regarding claim 19, Togawa teaches an intraoral examination method for measuring a signal intensity of a nucleic acid from an oral bacterial group present in an oral sample comprising calculating an abundance of the bacterial group (bacterial % or bacterial count) using next generation sequencing (performing 16S rRNA sequencing analysis with one or more bacteria), wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra (one or more bacteria selected from Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra), and determining a state of periodontal disease using the obtained calculated value as an index and comparing the obtained calculated value with a cut-off value of the abundance ratio of bacterial groups (comparing a bacterial % or bacterial count obtained through 16S rRNA sequencing analysis with that of patients with periodontitis) (paragraph [0039] lines 1-6; paragraph [0040] lines 1-5; paragraph [0041] lines 1-4; paragraph [0091] lines 1-5; paragraph [0098] lines 1-35).
Togawa does not teach that the comparison of the bacterial % or bacterial count with that of normal individuals and patients with periodontitis.
Tomás teaches a method for diagnosis of chronic (severe) periodontitis based on analysis of a group of bacterial species (one or more bacteria) comprising comparing the detection frequences and levels of the group of bacterial species (bacterial % or bacterial count) detected in subgingival sites with different periodontal conditions of a healthy control site (healthy individuals) and moderate to severe chronic (severe) periodontal site (patients with moderate or severe periodontitis) (abstract lines 1-32; pg. 2-3 paragraph bridging pg. 2 & 3 lines 1-18; pg. 4 column 2 1st full paragraph lines 1-15). Tomás also teaches that this method provides good predictive accuracy enabling improved patient monitoring and control of disease at the site-specific level (pg. 13-14 paragraph bridging pg. 13 & 14 lines 5-20).
Togawa and Tomás are considered to be analogous to the claimed invention because they are all in the same field of detection and quantification of bacterial species in patients with periodontitis. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using sequencing, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra and comparing the obtained calculated value with a cut-off value of the abundance ratio of bacterial groups in Togawa to incorporate comparing the detection frequences and levels of the group of bacterial species (bacterial % or bacterial count) with different periodontal conditions of a healthy control site (healthy individuals) and moderate to severe chronic (severe) periodontal site (patients with moderate or severe periodontitis) as taught in Tomás because Tomás teaches that doing so would provide a method with good predictive accuracy enabling improved patient monitoring and control of disease at the site-specific level.
Regarding claim 20, it is noted, as discussed above, the recitation of “wherein cut-off values are” in line 1 of the claim followed by the recitation of “and, if the bacterial % is greater than or equal to the corresponding cut-off value, healthy gums and periodontal diseases are distinguished” in lines 5-6 of the claim is unclear how the bacterial % is used to determine the cut-off values and how “if the bacterial % is greater than or equal to a corresponding cut-off value” distinguishes being healthy gums and periodontal diseases. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 1-4 of claim 20, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 1-4 in claim 20 due to the routine nature of reaction condition optimization.
Regarding claim 21, it is noted, as discussed above, the recitation of “wherein cut-off values are” in line 1 of the claim followed by the recitation of “and, if the bacterial % is greater than or equal to the corresponding cut-off value, healthy gum/gingivitis and periodontitis are distinguished” in lines 5-6 of the claim is unclear how the bacterial % is used to determine the cut-off values and how “if the bacterial % is greater than or equal to a corresponding cut-off value” distinguishes being healthy gums and periodontal diseases. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 1-4 of claim 21, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 1-4 in claim 21 due to the routine nature of reaction condition optimization.
Regarding claim 22, it is noted, as discussed above, the recitation of “wherein cut-off values are” in line 1 of the claim followed by the recitation of “and, if the bacterial % is greater than or equal to the corresponding cut-off value, healthy gum/gingivitis/moderate periodontitis and severe periodontitis are distinguished” in lines 4-6 of the claim is unclear how the bacterial % is used to determine the cut-off values and how “if the bacterial % is greater than or equal to a corresponding cut-off value” distinguishes being healthy gums and periodontal diseases. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 1-3 of claim 22, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 1-3 in claim 22 due to the routine nature of reaction condition optimization.
Regarding claim 23, Togawa teaches the oral sample collected from a subject comprises a saliva sample (paragraph [0162] lines 1-5).
Claim(s) 5, 6, 8, & 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Togawa (United States Patent Application Publication US 2021/0238659 A1, August 2021) and Tomás (Tomás et al.; Frontiers in Microbiology, Vol. 8, pages 1-16, August 2017), as cited in the IDS dated 04/11/2024, as applied to claims 1, 3, 4, 9, 13, 17, & 19-23 above, and further in view of Kook (WO 2012/134063 A2, April 2012), machine translation obtained from Science & Technical Information Center (STIC), GenBank Accession Number LC005376 (October 2017), GenBank Accession Number NR_114692 (March 2019), and GenBank Accession Number CP031971 (September 2018).
The teachings of Togawa and Tomás with respect to claims 1 & 3 is discussed above.
Regarding claims 5 & 6, Togawa and Tomás do not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 1-16.
Kook teaches a method for developing primers for detecting pathogenic bacteria of oral bacterial infectious diseases comprising SEQ ID NO: 27 and 28 for Porphyromonas gingivalis which represent SEQ ID NO: 1 & 2 of the instant application, SEQ ID NO: 85 and 86 for Tannerella forsythia which represent SEQ ID NO: 3 & 4 of the instant application, SEQ ID NO: 25 and 26 for Porphyromonas endodontalis which represent SEQ ID NO: 7 and 8, SEQ ID NO: 87 and 88 for Treponema denticola which represent SEQ ID NO: 11 and 12, and SEQ ID NO: 13 and 14 for Fusobacterium nucleatum which represent SEQ ID NO: 13 and 14 in the instant application (abstract lines 1-8; paragraph [10] lines 1-4; paragraph [12] lines 1-3; paragraph [17] lines 1-68). Kook also teaches that these primers have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis (abstract lines 4-8).
Kook does not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 5, 6, 9, 10, 15, & 16.
GenBank Accession Number LC005376 teaches the nucleic acid sequence of Prevotella intermedia which comprises the primers represented by SEQ ID NO: 5 and 6 of the instant application, GenBank Accession Number NR_114692 teaches the nucleic acid sequence of Filifactor alocis which comprises the primers represented by SEQ ID NO: 9 and 10 of the instant application, and GenBank Accession Number CP031971 teaches the nucleic acid sequence of Parvimonas micra which comprises the primers represented by SEQ ID NO: 15 and 16 of the instant application.
Togawa, Tomás, and Kook are considered to be analogous to the claimed invention because they are all in the same field of detection of oral bacteria in periodontitis with primers. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in Togawa to incorporate the primers represented by SEQ ID NOs: 1-4, 7, 8, & 11-14 as taught in Kook because Kook teaches that doing so would provide primers that have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis. In addition, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have modified Togawa, Tomás, and Kook, by constructing additional primers represented by SEQ ID NOs: 5, 6, 9, 10, 15, and 16 for measurement of the expression level of Prevotella intermedia, Filifactor alocis, and Parvimonas micra. The routine nature of constructing primers and/or probes for quantitative PCR is illustrated in the prior art cited (see Togawa, Tomás, and Kook). Therefore, absent secondary considerations, primers represented by SEQ ID NOs: 5, 6, 9, 10, 15, and 16 are considered obvious in view of the prior art cited.
Regarding claim 8, it is noted, as discussed above, the recitation of “based on a cut-off value of the bacterial count” in lines 2-3 of the claim is unclear what the relationship is between bacterial count and a cut-off value or how the bacterial count is used to obtain a cut-off value. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-11 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 5-12 of claim 8, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 5-12 in claim 8 due to the routine nature of reaction condition optimization.
Togawa and Tomás do not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 1-16.
Kook teaches a method for developing primers for detecting pathogenic bacteria of oral bacterial infectious diseases comprising SEQ ID NO: 27 and 28 for Porphyromonas gingivalis which represent SEQ ID NO: 1 & 2 of the instant application, SEQ ID NO: 85 and 86 for Tannerella forsythia which represent SEQ ID NO: 3 & 4 of the instant application, SEQ ID NO: 25 and 26 for Porphyromonas endodontalis which represent SEQ ID NO: 7 and 8, SEQ ID NO: 87 and 88 for Treponema denticola which represent SEQ ID NO: 11 and 12, and SEQ ID NO: 13 and 14 for Fusobacterium nucleatum which represent SEQ ID NO: 13 and 14 in the instant application (abstract lines 1-8; paragraph [10] lines 1-4; paragraph [12] lines 1-3; paragraph [17] lines 1-68). Kook also teaches that these primers have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis (abstract lines 4-8).
Kook does not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 5, 6, 9, 10, 15, & 16.
GenBank Accession Number LC005376 teaches the nucleic acid sequence of Prevotella intermedia which comprises the primers represented by SEQ ID NO: 5 and 6 of the instant application, GenBank Accession Number NR_114692 teaches the nucleic acid sequence of Filifactor alocis which comprises the primers represented by SEQ ID NO: 9 and 10 of the instant application, and GenBank Accession Number CP031971 teaches the nucleic acid sequence of Parvimonas micra which comprises the primers represented by SEQ ID NO: 15 and 16 of the instant application.
Togawa, Tomás, and Kook are considered to be analogous to the claimed invention because they are all in the same field of detection of oral bacteria in periodontitis with primers. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in Togawa to incorporate the primers represented by SEQ ID NOs: 1-4, 7, 8, & 11-14 as taught in Kook because Kook teaches that doing so would provide primers that have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis. In addition, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have modified Togawa, Tomás, and Kook, by constructing additional primers represented by SEQ ID NOs: 5, 6, 9, 10, 15, and 16 for measurement of the expression level of Prevotella intermedia, Filifactor alocis, and Parvimonas micra. The routine nature of constructing primers and/or probes for quantitative PCR is illustrated in the prior art cited (see Togawa, Tomás, and Kook). Therefore, absent secondary considerations, primers represented by SEQ ID NOs: 5, 6, 9, 10, 15, and 16 are considered obvious in view of the prior art cited.
Regarding claim 12, it is noted, as discussed above, the recitation of “based on a cut-off value of the bacterial count” in lines 2-3 of the claim is unclear what the relationship is between bacterial count and a cut-off value or how the bacterial count is used to obtain a cut-off value. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-13 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 5-13 of claim 12, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 5-13 in claim 12 due to the routine nature of reaction condition optimization.
Togawa and Tomás do not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 1-16.
Kook teaches a method for developing primers for detecting pathogenic bacteria of oral bacterial infectious diseases comprising SEQ ID NO: 27 and 28 for Porphyromonas gingivalis which represent SEQ ID NO: 1 & 2 of the instant application, SEQ ID NO: 85 and 86 for Tannerella forsythia which represent SEQ ID NO: 3 & 4 of the instant application, SEQ ID NO: 25 and 26 for Porphyromonas endodontalis which represent SEQ ID NO: 7 and 8, SEQ ID NO: 87 and 88 for Treponema denticola which represent SEQ ID NO: 11 and 12, and SEQ ID NO: 13 and 14 for Fusobacterium nucleatum which represent SEQ ID NO: 13 and 14 in the instant application (abstract lines 1-8; paragraph [10] lines 1-4; paragraph [12] lines 1-3; paragraph [17] lines 1-68). Kook also teaches that these primers have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis (abstract lines 4-8).
Kook does not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 5, 6, 9, 10, 15, & 16.
GenBank Accession Number LC005376 teaches the nucleic acid sequence of Prevotella intermedia which comprises the primers represented by SEQ ID NO: 5 and 6 of the instant application, GenBank Accession Number NR_114692 teaches the nucleic acid sequence of Filifactor alocis which comprises the primers represented by SEQ ID NO: 9 and 10 of the instant application, and GenBank Accession Number CP031971 teaches the nucleic acid sequence of Parvimonas micra which comprises the primers represented by SEQ ID NO: 15 and 16 of the instant application.
Togawa, Tomás, and Kook are considered to be analogous to the claimed invention because they are all in the same field of detection of oral bacteria in periodontitis with primers. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in Togawa to incorporate the primers represented by SEQ ID NOs: 1-4, 7, 8, & 11-14 as taught in Kook because Kook teaches that doing so would provide primers that have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis. In addition, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have modified Togawa, Tomás, and Kook, by constructing additional primers represented by SEQ ID NOs: 5, 6, 9, 10, 15, and 16 for measurement of the expression level of Prevotella intermedia, Filifactor alocis, and Parvimonas micra. The routine nature of constructing primers and/or probes for quantitative PCR is illustrated in the prior art cited (see Togawa, Tomás, and Kook). Therefore, absent secondary considerations, primers represented by SEQ ID NOs: 5, 6, 9, 10, 15, and 16 are considered obvious in view of the prior art cited.
Claim(s) 7 & 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Togawa (United States Patent Application Publication US 2021/0238659 A1, August 2021) and Tomás (Tomás et al.; Frontiers in Microbiology, Vol. 8, pages 1-16, August 2017), as cited in the IDS dated 04/11/2024, as applied to claims 1, 3, 4, 9, 13, 17, & 19-23 above, and further in view of Kook (WO 2012/134063 A2, April 2012), machine translation obtained from Science & Technical Information Center (STIC), GenBank Accession Number LC005376 (October 2017), and GenBank Accession Number NR_114692 (March 2019).
The teachings of Togawa and Tomás with respect to claim 3 is discussed above.
Regarding claim 7, it is noted, as discussed above, the recitation of “based on a cut-off value of the bacterial %” in lines 2-3 of the claim is unclear what the relationship is between bacterial % and a cut-off value or how the bacterial % is used to obtain a cut-off value. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-9 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 5-10 of claim 7, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 5-10 in claim 7 due to the routine nature of reaction condition optimization.
Togawa and Tomás do not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 1-10.
Kook teaches a method for developing primers for detecting pathogenic bacteria of oral bacterial infectious diseases comprising SEQ ID NO: 27 and 28 for Porphyromonas gingivalis which represent SEQ ID NO: 1 & 2 of the instant application, SEQ ID NO: 85 and 86 for Tannerella forsythia which represent SEQ ID NO: 3 & 4 of the instant application, and SEQ ID NO: 25 and 26 for Porphyromonas endodontalis which represent SEQ ID NO: 7 and 8 (abstract lines 1-8; paragraph [10] lines 1-4; paragraph [12] lines 1-3; paragraph [17] lines 1-68). Kook also teaches that these primers have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis (abstract lines 4-8; paragraph [10] lines 1-4).
Kook does not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 5, 6, 9, & 10.
GenBank Accession Number LC005376 teaches the nucleic acid sequence of Prevotella intermedia which comprises the primers represented by SEQ ID NO: 5 and 6 of the instant application and GenBank Accession Number NR_114692 teaches the nucleic acid sequence of Filifactor alocis which comprises the primers represented by SEQ ID NO: 9 and 10 of the instant application.
Togawa, Tomás, and Kook are considered to be analogous to the claimed invention because they are all in the same field of detection of oral bacteria in periodontitis with primers. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in Togawa to incorporate the primers represented by SEQ ID NOs: 1-4, 7, & 8 as taught in Kook because Kook teaches that doing so would provide primers that have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis. In addition, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have modified Togawa, Tomás, and Kook, by constructing additional primers represented by SEQ ID NOs: 5, 6, 9, and 10 for measurement of the expression level of Prevotella intermedia and Filifactor alocis. The routine nature of constructing primers and/or probes for quantitative PCR is illustrated in the prior art cited (see Togawa, Tomás, and Kook). Therefore, absent secondary considerations, primers represented by SEQ ID NOs: 5, 6, 9, and 10 are considered obvious in view of the prior art cited.
Regarding claim 16, it is noted, as discussed above, the recitation of “based on a cut-off value of the bacterial count” in lines 2-3 of the claim is unclear what the relationship is between bacterial count and a cut-off value or how the bacterial count is used to obtain a cut-off value. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 4-9 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 5-10 of claim 16, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 5-10 in claim 16 due to the routine nature of reaction condition optimization.
Togawa and Tomás do not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 1-6, 9, 10, 13, & 14.
Kook teaches a method for developing primers for detecting pathogenic bacteria of oral bacterial infectious diseases comprising SEQ ID NO: 27 and 28 for Porphyromonas gingivalis which represent SEQ ID NO: 1 & 2 of the instant application, SEQ ID NO: 85 and 86 for Tannerella forsythia which represent SEQ ID NO: 3 & 4 of the instant application, SEQ ID NO: 25 and 26 for Porphyromonas endodontalis which represent SEQ ID NO: 7 and 8, and SEQ ID NO: 13 and 14 for Fusobacterium nucleatum which represent SEQ ID NO: 13 and 14 in the instant application (abstract lines 1-8; paragraph [10] lines 1-4; paragraph [12] lines 1-3; paragraph [17] lines 1-68). Kook also teaches that these primers have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis (abstract lines 4-8; paragraph [10] lines 1-4).
Kook does not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 5, 6, 9, & 10.
GenBank Accession Number LC005376 teaches the nucleic acid sequence of Prevotella intermedia which comprises the primers represented by SEQ ID NO: 5 and 6 of the instant application and GenBank Accession Number NR_114692 teaches the nucleic acid sequence of Filifactor alocis which comprises the primers represented by SEQ ID NO: 9 and 10 of the instant application.
Togawa, Tomás, and Kook are considered to be analogous to the claimed invention because they are all in the same field of detection of oral bacteria in periodontitis with primers. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in Togawa to incorporate the primers represented by SEQ ID NOs: 1-4, 7, 8, 13, & 14 as taught in Kook because Kook teaches that doing so would provide primers that have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis. In addition, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have modified Togawa, Tomás, and Kook, by constructing additional primers represented by SEQ ID NOs: 5, 6, 9, and 10 for measurement of the expression level of Prevotella intermedia and Filifactor alocis. The routine nature of constructing primers and/or probes for quantitative PCR is illustrated in the prior art cited (see Togawa, Tomás, and Kook). Therefore, absent secondary considerations, primers represented by SEQ ID NOs: 5, 6, 9, and 10 are considered obvious in view of the prior art cited.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Togawa (United States Patent Application Publication US 2021/0238659 A1, August 2021) and Tomás (Tomás et al.; Frontiers in Microbiology, Vol. 8, pages 1-16, August 2017), as cited in the IDS dated 04/11/2024, as applied to claims 1, 3, 4, 9, 13, 17, & 19-23 above, and further in view of Kook (WO 2012/134063 A2, April 2012), machine translation obtained from Science & Technical Information Center (STIC).
The teachings of Togawa and Tomás with respect to claim 3 is discussed above.
Regarding claim 11, it is noted that the recitation of “based on a cut-off value of the bacterial %” in lines 2-3 of the claim is unclear what the relationship is between bacterial % and a cut-off value or how the bacterial % is used to obtain a cut-off value. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 3-5 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 5-6 of claim 11, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 5-6 in claim 11 due to the routine nature of reaction condition optimization.
Togawa and Tomás do not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 1-4.
Kook teaches a method for developing primers for detecting pathogenic bacteria of oral bacterial infectious diseases comprising SEQ ID NO: 27 and 28 for Porphyromonas gingivalis which represent SEQ ID NO: 1 & 2 of the instant application and SEQ ID NO: 85 and 86 for Tannerella forsythia which represent SEQ ID NO: 3 & 4 of the instant application (abstract lines 1-8; paragraph [10] lines 1-4; paragraph [12] lines 1-3; paragraph [17] lines 1-68). Kook also teaches that these primers have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis (abstract lines 4-8; paragraph [10] lines 1-4).
Togawa, Tomás, and Kook are considered to be analogous to the claimed invention because they are all in the same field of detection of oral bacteria in periodontitis with primers. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in Togawa to incorporate the primers represented by SEQ ID NOs: 1-4 as taught in Kook because Kook teaches that doing so would provide primers that have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Togawa (United States Patent Application Publication US 2021/0238659 A1, August 2021) and Tomás (Tomás et al.; Frontiers in Microbiology, Vol. 8, pages 1-16, August 2017), as cited in the IDS dated 04/11/2024, as applied to claims 1, 3, 4, 9, 13, 17, & 19-23 above, and further in view of Kook (WO 2012/134063 A2, April 2012), machine translation obtained from Science & Technical Information Center (STIC) and GenBank Accession Number LC005376 (October 2017).
The teachings of Togawa and Tomás with respect to claim 3 is discussed above.
Regarding claim 15, it is noted, as discussed above, the recitation of “based on a cut-off value of the bacterial %” in lines 2-3 of the claim is unclear what the relationship is between bacterial % and a cut-off value or how the bacterial % is used to obtain a cut-off value. In addition, the recitation of “the cut-off value of the target gene of the primer set represented by SEQ ID NOS:” in lines 4-7 is unclear how the cut-off value of the target gene of the primer set represented by the respective SEQ ID NOS: are related. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to comprise determining cut-off values for measured bacterial species and using bacterial % and determined cut-off value to distinguish between healthy gums and periodontal diseases.
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected (AUC value greater than or equal to 0.7) to distinguish healthy versus periodontitis sites (healthy gums and gums with periodontal disease based on the bacterial % or bacterial count) (pg. 5 column 1 5th full paragraph lines 1-3; pg. 5 column 2 1st full paragraph lines 1-12; pg. 5 column 2 2nd full paragraph lines 1-11).
Tomás does not teach the specific cut-off values listed in lines 5-7 of claim 15, however, the cut-off value is prima facie obvious in view of the routine nature of reaction condition optimization as taught in Tomás. As set forth in the MPEP 2144.05IIA:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)
Tomás teaches determining the best cut-off value to provide a percentage of correct predictions that was maximum from detection frequencies and levels of a group of bacterial species (bacterial % or bacterial count) through ROC curve analysis where an AUC of 0.76 or above were selected. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of determining the best cut-off values from detection frequencies and levels of a group of bacterial species in healthy and periodontal samples as taught in Tomás to obtain the specific cut-off values listed in lines 5-7 in claim 15 due to the routine nature of reaction condition optimization.
Togawa and Tomás do not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 1-6.
Kook teaches a method for developing primers for detecting pathogenic bacteria of oral bacterial infectious diseases comprising SEQ ID NO: 27 and 28 for Porphyromonas gingivalis which represent SEQ ID NO: 1 & 2 of the instant application and SEQ ID NO: 85 and 86 for Tannerella forsythia which represent SEQ ID NO: 3 & 4 of the instant application (abstract lines 1-8; paragraph [10] lines 1-4; paragraph [12] lines 1-3; paragraph [17] lines 1-68). Kook also teaches that these primers have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis (abstract lines 4-8; paragraph [10] lines 1-4).
Kook does not teach the quantitative analysis by real-time PCR measures and expression level using one or more primer sets represented by SEQ ID NOs: 5 & 6.
GenBank Accession Number LC005376 teaches the nucleic acid sequence of Prevotella intermedia which comprises the primers represented by SEQ ID NO: 5 and 6 of the instant application.
Togawa, Tomás, and Kook are considered to be analogous to the claimed invention because they are all in the same field of detection of oral bacteria in periodontitis with primers. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of calculating an abundance of the bacterial group (bacterial % or bacterial count) using real-time PCR, wherein the detection bacteria comprise Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Filifactor alocis, Fusobacterium nucleatum, and Parvimonas micra in Togawa to incorporate the primers represented by SEQ ID NOs: 1-4 as taught in Kook because Kook teaches that doing so would provide primers that have high species specificity and can quickly and simply detect oral bacteria in periodontal tissue as a tool for bacteriological assessment of prognosis. In addition, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have modified Togawa, Tomás, and Kook, by constructing additional primers represented by SEQ ID NOs: 5 and 6 for measurement of the expression level of Prevotella intermedia and Filifactor alocis. The routine nature of constructing primers and/or probes for quantitative PCR is illustrated in the prior art cited (see Togawa, Tomás, and Kook). Therefore, absent secondary considerations, primers represented by SEQ ID NOs: 5 and 6 are considered obvious in view of the prior art cited.
Conclusion
Claims 1, 3-9, 11-13, 15-17, & 19-23 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/ Primary Examiner, Art Unit 1682
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