DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
1. Claims 1-2 and 7-9 are pending and subject to examination on the merits. Claim 2 is withdrawn from consideration as being drawn to non-elected subject matter. Claims 1 and 7-9 are currently under examination.
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10 June 2026 has been entered.
Priority
3. Acknowledgment is made for the Applicant’s claim for domestic priority based on the US provisional application PRO 62/930,147 filed 04 November 2019.
Withdrawn Rejections
4. The rejection of claims 1 and 4-9 under 35 U.S.C. 101 as unpatentable for directed to a judicial exception without substantially more to integrate it into practical application is withdrawn, since claim 1 was amended to recite “wherein the treating is selected from the group consisting of…,” which were originally limitations found in cancelled claims, 4-6, specifically the addition of a treatment step to asymptomatic patients with any probiotic bacteria, prebiotic compounds, antibiotics, and antimicrobials, and additionally, a mixture of a probiotics and prebiotics. The original rejection included these limitations at least and included symptomatic. The original rejection has been withdrawn in view of the modified rejection below.
5. The rejection of claims 1 and 4-5 under 35 U.S.C. 103 as being unpatentable over Gilbert et al. (Gilbert et al., 2013, PLOS ONE—cited on the Information Disclosure Statement dated 10 August 2022), Anderson et al (Anderson et al., 2014, Am J Reprod Immunol--cited on the Information Disclosure Statement dated 15 November 2023), and Amegashie et al (Amegashie et al., 2017, PLOS ONE—cited on the Information Disclosure Statement dated 15 November 2023), and Akins and Sobel (Akins and Sobel, 2019, US2019/0264263 A1—cited on the information disclosure statement dated 10 August 2022) is withdrawn, since claim 1 was modified to include the claim limitation of claim 4, asymptomatic, and deleted the claim limitation of claim 5, symptomatic, from the instant claims. Said rejection has been withdrawn in view of the modified rejection below.
6. The rejection of claims 6-9 under 35 U.S.C. 103 as being unpatentable over Gilbert et al. (Gilbert et al., 2013, PLOS ONE—cited on the Information Disclosure Statement dated 10 August 2022), Anderson et al (Anderson et al., 2014, Am J Reprod Immunol--cited on the Information Disclosure Statement dated 15 November 2023), and Amegashie et al (Amegashie et al., 2017, PLOS ONE—cited on the Information Disclosure Statement dated 15 November 2023), and Akins and Sobel (Akins and Sobel, 2019, US2019/0264263 A1—cited on the information disclosure statement dated 10 August 2022) as applied to claims 1 and 4-5 above, and further in view of Verstraelen and Verhelst (Verstraelen and Verhelst, 2009, Expert Rev. Anti Infect. Ther—cited previously) is withdrawn, since claim 1 was modified to include the claim limitation of claim 4, asymptomatic, and deleted the claim limitation of claim 5, symptomatic, from the instant claims. Additionally, the claim limitations of claim 6, i.e. the administration to a subject probiotic bacteria, prebiotic compounds, a mixture of probiotic and prebiotics, and antibiotics and antimicrobials was added claim 1. Therefore, said rejection has been withdrawn in view of the modified rejection below.
Claim Rejections - 35 USC § 101
7. 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.
8. Claims 1 and 7-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon) without additional elements that integrate the judicial exception into a practical application. An analysis with respect to the claims as a whole reveals that they do not include additional elements that integrate the judicial exception into a practical application. See MPEP 2106.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of the following steps:
Step (1) whether the claim is directed to one of the four categories recited in §101 (process, machine, manufacture or composition of matter);
Step (Revised 2A - Prong 1) do the claims recite an abstract idea (mathematical concepts, mental processes or method of organizing human activity), law of nature or natural phenomenon;
Step (Revised 2A - Prong 2) do the claims recite additional elements that integrate the judicial exception into a practical application; and
Step (2B) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. (See 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG)).
Step 1: Yes; the claims are directed to a process.
Step 2A – Prong 1: Yes, the claims recite a natural correlation of the process and/or mental process of quantifying shed epithelial cells as a diagnostic feature of bacterial vaginosis and subsequently treating the infection in asymptomatic individuals, where treatment is selected from any conventional treatment, specifically, antimicrobials, antibiotics, prebiotics, or the application of a probiotic bacteria, Lactobacillus casei (claims 7-8) or an antimicrobial consisting of boric acid (claim 9).
Step 2A – Prong 2: No, the claims do not recite any additional elements that integrate the judicial exception into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there is no other meaningful limitations not already present when the elements are considered separately; i.e. they are solely directed to a naturally occurring correlation of cell counts that inform of stages of bacterial vaginosis, wherein the correlation is identified by a mental process (e.g. abstract idea), and then, merely conventional methods and conventional treatments are utilized (See MPEP 2106.04(a)(2)(III) and all of 2106.04 and 2106.05).
Step 2B: As noted in answering that of 2A – This judicial exception is not integrated into a practical application because the additional elements considered together or separately are conventional methods well-known in the art. Obtaining vaginal secretions and doing epithelial cell counts is routine to the art and merely identifying the natural correlation that exists in nature between the amount of total cell shed counts, superficial cells counts and parabasal cell counts does not transform what already exists in nature for these cells. Furthermore, treating by any or all conventional means known in the art as such a level of generality (e.g. essentially telling those to “apply it” for the exception – See MPEP 2106.05(f) and 2106.04(d)), does not transform these method claims either.
As such, the claims do not amount to more than a known a naturally occurring correlation between kinds of cells and their counts and the states, and essentially of a mental process of identifying said correlation of said bacterial vaginosis and a subsequent generic method to treat said bacterial vaginosis by well-known and conventional methods, i.e. the application of a antibiotics, probiotics/prebiotics and/or boric acid (See Verstraelen and Verhelst, abstract; p. 10, paragraph 2; p. 8, 2nd column).
Claim Rejections - 35 USC § 103
9. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
10. 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.
11. Claims 1 and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Gilbert et al. (Gilbert et al., 2013, PLOS ONE—cited on the Information Disclosure Statement dated 10 August 2022), Anderson et al (Anderson et al., 2014, Am J Reprod Immunol--cited on the Information Disclosure Statement dated 15 November 2023), and Amegashie et al (Amegashie et al., 2017, PLOS ONE—cited on the Information Disclosure Statement dated 15 November 2023), and Akins and Sobel (Akins and Sobel, 2019, US2019/0264263 A1—cited on the information disclosure statement dated 10 August 2022) and further in view of Verstraelen and Verhelst (Verstraelen and Verhelst, 2009, Expert Rev. Anti Infect. Ther—cited previously). Regarding claim 1, drawn to a method of diagnosing the stage of bacterial vaginosis by obtaining a sample of vaginal secretion from the subject, determining the total number of shed epithelial cells, and determining the maturity of said shed epithelial cells for superficial cells and parabasal cells in the sample to diagnose Stage I or Stage II of bacterial vaginosis, wherein Stage I is diagnosed with the total cell shedding log10 cell count is from about 2.4- about 3.0, superficial cells log10 cell count from about 1.5- about 2.7, and parabasal cells log 10 cell count is from about 1.1 to about 2.5, and wherein Stage II bacterial vaginosis is diagnosed when total cell shedding log10 cell count is from about 1.5- about 2.5, superficial cells log10 cell count is about 1.0- about 1.7, and parabasal cells log10 cell count is about 1.2- about 2.3, and treating Stage II BV in the asymptomatic subject, wherein the treating is selected from the group consisting of administering to the subject of (a) probiotic bacteria, (b) prebiotic compounds, (c) a mixture of probiotic bacteria and prebiotic compounds, (d) antibiotics, and antimicrobials, Gilbert et al. teaches a method of diagnosing the stage of bacterial vaginosis in a subject by utilizing a murine model with a clinical isolate of Gardnerella vaginalis (Abstract; lines 2-5). Gilbert continues to a measurable epithelial exfoliation in clinical samples from women with bacterial vaginosis (BV) response compared to women with normal flora (Abstract; lines 11-12). Specifically, Gilbert et al. teach obtaining a sample from vaginal secretion from the subject via vaginal swabs as part of the contraceptive CHOICE project. Gilbert et al. then teach gram staining and analyzing for epithelial exfoliation by enumerating epithelial cells in samples from bacterial vaginosis positive and negative patients, where there is an increase in the total epithelial cells per field in BV+ vs. BV- samples (p. 11, column 2, Clinical Specimen Handling and Analysis of epithelial Exfoliation; Fig. 7). Gilbert et al. teaches that the increase of shed epithelial cells was positively correlated with the CFU (BV) found in the sample (Fig. 6C; p. 4, column 2, paragraph 2). Therefore, increased CFU led to an increase in shed epithelial cells.
Gilbert et al. does not teach the determination of the total number of shed cells in log10 count and the maturity of the epithelial cells as superficial and parabasal. Anderson et al. teaches that the vaginal epithelium undergoes differentiation and contains several distinct layers or “strata,” including the basal layer, the superbasal layer, and a superficial layer (p. 618 last line- p. 619 line 5), where the superficial cells consist of keratinized enucleated, dead, and flattened cells (p. 619; lines 10-12) and the parabasal cells consist of mitotically active cells (p. 619, line 10) (See Fig. 1B). Anderson et al. continues to teach that exfoliation of the cell layers is an effective way to eliminate pathogens that have attached to the vaginal surface or that bind to sloughed ‘decoy’ cells (p. 619, last paragraph-p. 621, first paragraph).
Gilbert et al. and Anderson et al. do not specifically teach Stage I and Stage II BV. Amegashie et al. teaches BV-, BVint, and BV+ cohorts, corresponding to Nugent scores, where BV- is Nugent 0-3, BVint is Nugent 4-6, and BV+ is Nugent 7-10) (p. 3, second paragraph). Amegashie et al. continue to teach that the previous study (Gilbert et al.) did not test the epithelial exfoliation among all three groupings of Nugent scores, i.e. the inclusion of BVint (p. 2, last paragraph). Amegashie et al. continues to teach an increase in epithelial exfoliation in both BVint and BV+ samples (Fig. 1).
Regarding the cell numbers recited in the claim, Amegashie et al. demonstrates counting epithelial cells in the microscope fields and an increase in epithelial cells shed in BVint and BV+ samples (Fig. 1). Utilizing a known dilution factor and total fluid volume, it would be routine to a person of ordinary skill in the art, to obtain cell counts of total epithelial cells. Obtaining the ranges recited in the claim would therefore be routine optimization.
Routine optimization to determine the optimal working conditions of an invention is not non-obvious. The MPEP states, "[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). See MPEP Section 2144.05.
The teachings of Gilbert et al., Anderson et al., and Amegashie et al. do not teach a method of treating bacterial vaginosis based on the results of the diagnostic method. Regarding treating the subject for bacterial vaginosis if the subject is diagnosed with asymptomatic Stage II BV, Akins and Sobel teach a method of identifying and treating individuals for BV recurrence that are asymptomatic by obtaining a vaginal sample after a course of treatment for BV, amplifying the bacterial DNA present, determining the cycle (Cq) score for unblocked samples and subtracting the Cq of the blocked samples, and predicting recurrence of BV in the subject if the ΔCq is below 3 and asymptomatic, where that subject is then the subject is treated and treatment assessed for effectiveness (claim 20, paragraphs 0084, 0116-0117).
Gilbert et al., Anderson et al., Amegashe et al., and Akins and Sobel do not teach the treatment of BV with probiotics, such as L. casei (claims 1, and 7-8), or boric acid (claims 1 and 9). Verstraelen and Verhelst teach that bacterial vaginosis can be treated with alternative treatments, such as vaginal acidifying and buffering agents and probiotics for long term prevention (abstract). Specifically, Verstraelen and Verhelst teach alternative or adjuvant treatment with probiotics, such as Lactobacillus sp. and Bifidobacterium sp., including Lactobacillus casei (p. 8, column 2). Additionally, Verstraelen and Verhelst teach the utilization of boric acid in treating recurrent BV (p. 10, paragraph 2
Therefore, it 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 combine the teachings of Gilbert et al., Anderson et al., Amegashie et al., Akins and Sobel, and Verstraelen and Verhelst to devise a method of identifying symptomatic and asymptomatic BV patients by enumerating exfoliated epithelial cells and subsequently treating said patients to assess the health of a microbiome and further categorize non-dominant species populations in samples as taught by Amegashie et al (paragraph 0034). Additionally, it would be obvious to a person having ordinary skill in the art to treat BV with probiotics or boric acid because they serve as an adjuvant to standard treatments with antibiotics and hold promise for long-term prevention as taught by Verstraelen and Verhelst (abstract). One would be motivated to combine these teachings to arrive at the instant claims to mitigate the risks from BV, such as increased susceptibility to HIV, infections following surgical procedures, such as hysterectomies or abortions, complications from pregnancy, and susceptibility to other STDs, such as herpes simplex virus, chlamydia, and gonorrhea. Further, one would be motivated to combine these teachings to arrive at the instant claims to reduce infection with secondary agents, such as T. vaginalis, N. gonorrhoeae, C. trachomatis, HSV-2, and HIV-1, as taught by Verstraelen and Verhelst (p. 1, bottom of first column). There would be a reasonable expectation of success, yielding no surprising results when combining the teachings of Gilbert et al., Anderson et al., and Amegashie et al., Akins and Sobel, and Verstraelen and Verhelst, since Akins and Sobel describe treating asymptomatic BV patients and since Verstraelen and Verhelst teach probiotic and boric acid treatment of recurrent BV.
Applicant’s Arguments and Examiner’s Rebuttal:
The applicant traverses the previous rejections of record, including the 35 U.S.C. 101 rejection over a judicial exception in the absence of more to put it into practical application and previous obviousness rejections: The rejection of claims 1 and 4-5 under 35 U.S.C. 103 as being unpatentable over Gilbert et al. (Gilbert et al., 2013, PLOS ONE—cited on the Information Disclosure Statement dated 10 August 2022), Anderson et al (Anderson et al., 2014, Am J Reprod Immunol--cited on the Information Disclosure Statement dated 15 November 2023), and Amegashie et al (Amegashie et al., 2017, PLOS ONE—cited on the Information Disclosure Statement dated 15 November 2023), and Akins and Sobel (Akins and Sobel, 2019, US2019/0264263 A1—cited on the information disclosure statement dated 10 August 2022) and the rejection of claims 6-9 under 35 U.S.C. 103 as being unpatentable over Gilbert et al. (Gilbert et al., 2013, PLOS ONE—cited on the Information Disclosure Statement dated 10 August 2022), Anderson et al (Anderson et al., 2014, Am J Reprod Immunol--cited on the Information Disclosure Statement dated 15 November 2023), and Amegashie et al (Amegashie et al., 2017, PLOS ONE—cited on the Information Disclosure Statement dated 15 November 2023), and Akins and Sobel (Akins and Sobel, 2019, US2019/0264263 A1—cited on the information disclosure statement dated 10 August 2022) as applied to claims 1 and 4-5 above, and further in view of Verstraelen and Verhelst (Verstraelen and Verhelst, 2009, Expert Rev. Anti Infect. Ther—cited previously). The rejections were modified above to include the new claim limitations.
The applicant argues first that the claim recites additional elements that amount significantly more than the natural phenomenon of cell counts in the diagnosis of BV. Specifically, the applicant argues the collection of vaginal secretion is not a natural phenomenon. The examiner respectfully disagrees because there is no manipulation of the secretion. It is only utilized a starting material to then count and rate cells based on maturity. The applicant continues to argue that the diagnosis based on cell counts is an active step. The examiner respectfully disagrees because the diagnosis is made due to a correlation of the cell material, i.e. a population of cells representative of a certain maturity, which would therefore constitute a mental process not an active step. Last, the applicant argues that the treatment step is the practical application of the correlated cells in BV. However, as currently recited, the examiner respectfully disagrees because the claim only recites the treatment of a known disease after a correlative count of cells to determine BV state and a subsequent generic method to treat said bacterial vaginosis by well-known and conventional methods, i.e. the application of a antibiotics, probiotics/prebiotics and/or boric acid (See Verstraelen and Verhelst, abstract; p. 10, paragraph 2; p. 8, 2nd column). The applicant then asserts that the instant claims and those of Vanda, where the limitation from previous claim 6 has been incorporated into claim 1, are similar in that they both “recite an action that effects a particular treatment or prophylaxis for a disease or medical condition.” While there may now be a recitation of a generic treatment method in claim 1 (previously in claim 6), the examiner does not agree that the recitation of any and all conventional treatments after the correlation of cell types in a BV subject is enough to overcome the rejection (See MPEP 2106.04(a)(2)(III) and all of 2106.04 and 2106.05).
The applicant then argues that taking action in treating asymptomatic Stage II BV is not a natural phenomenon. However, the examiner respectfully disagrees, since many women who would presumably be asymptomatic for BV still take or have taken prebiotics and probiotics for vaginal health. Therefore, the examiner contends that the natural phenomenon or process here of correlating cell counts to Stage II BV and treating said disease with prebiotics and probiotics is a natural phenomenon, specifically a process, found in the normal female population.
Next, the applicant argues that claim 1 has been amended to include all of the features of claim 6, which was not rejected in the first obviousness of record in the last office action, where claims 1 and 4-5 were rejected under 35 U.S.C. 103 over Gilbert, Anderson, Amegashie, and Akins. However, the new 35 U.S.C. 103 obviousness rejection of record above (over Gilbert, Anderson, Amegashie, Akins, and Verstraelen and Verhelst does address the newly added claim amendments.
Last, the applicant incorporates of the previous remarks and arguments from the previous office action. The responses to these office actions are found below (for convenience):
“Second, regarding the 35 U.S.C. 103 rejection, the applicant argues that Gilbert et al. does not teach a method to diagnose BV and/or the stages of BV by enumerating epithelial cells. The examiner agrees insofar that Gilbert et al. was not relied upon to anticipate the current method; therefore, Gilbert et al. does not teach all aspects of the current invention. Gilbert et al. does teach enumeration of epithelial cells and demonstrates a positive correlation between uninfected and infected individuals (as presented above).
Third, the applicant argues that Anderson et al. does not teach BV or a way to diagnose BV. The examiner agrees insofar that the Anderson et al. reference was not utilized to anticipate the instant claims. The Anderson et al. reference was introduced to teach the cell layers present in the vaginal tissue and the natural phenomenon that is cellular exfoliation, especially when exposed to a pathogen.
Fourth, the applicant argues that Amegashe et al. did not distinguish between the Stage I and Stage II BV with the epithelial cell counts. The examiner agrees insofar that Amagashe et al. did not recite the ranges of the instant claim or set out to determine these recited ranges; however, as described above, the recited ranges are considered optimization to the examiner. These ranges could be and would be determined by routine optimization through cell counting by a skilled artisan.
Fifth, the applicant argues that a skilled artisan would not be motivated nor they have a reasonable chance of success to correlate bacterial counts and epithelial cell counts to guess whether epithelial cell counts were even relevant to BV diagnosis or to come up with the precise claims presented. The examiner disagrees. Gilbert et al. and Amagahe et al. both determine a correlation between epithelial cell counts and BV. Although the instant claims recite specific ranges and define those ranges in an asymptomatic vs. symptomatic infection, a skilled artisan would still be able to a) correlate the epithelial shedding vs. bacterial infection, since Gilbert et al. and Amagashe et al. both demonstrated this previously, and b) optimize the cell counts, since this is a routine method utilized in the field, as demonstrated by all three references, Gilbert et al., Amagashe et al., and Anderson et al., where specifically, each are able to count shed cells and correlate said number to a disease state.
Sixth, the applicant argues that the second obviousness rejection is entirely moot, since claim 3 was deleted, and claims 4-5 now depend from claim 1. These claims and claim amendments are addressed in the above, new 35 U.S.C. 103 rejection of obviousness found above over Gilbert et al., Anderson et al., and Amegashie et al. with Akins and Sobel.” (previous Final Rejection; mail date 05 March 2026; p. 11-12).
The examiner does not find the arguments presented by the applicant persuasive, and for these reasons, the rejections of record above apply.
Conclusion
12. All claims are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Prosecution Insights