DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 19 November 2025. Claims 25, 30-32, 37, 40, and 41 have been amended. Claims 24 and 32-35 remain withdrawn. Claims 25-31 and 36-42 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/US2020/044050, filed 29 July 2020, which claims priority to U.S. Provisional Application No. 62/879943, filed 29 July 2019.
Withdrawal of Objections/Rejections:
The objection to 41, is withdrawn.
The rejection of claims 25-31, 36, and 40-42 only under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn.
The rejection of claim 40 only under 35 U.S.C. 103 as being unpatentable over Wade et al., in view of Bassir et al., is withdrawn.
Maintenance/Modification of Rejections Necessitated by Amendment:
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 37-39 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.
With regard to claim 37, the term “reduces” is a relative term which renders the claim indefinite. The term “reduces” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Here, it is unclear what amount of reduction is intended to be included in, or excluded from, “reducing” a bacterial infection. Further, it is noted that a bacterial infection is not indicated as being present in claim 25. As such, it is unclear how a bacterial infection that is not present is to be reduced.
With regard to claim 39, this claim is still indefinite, because it is unclear what a small molecule inhibitor of Porphyromonas gingivalis is intended to encompass. There is no guidance in the specification providing any indication of what agent this is intended to be.
Claim 38 is included in this rejection, as this claim depends from above rejected claim 37, and fails to remedy the noted deficiencies.
Response to Arguments
With regard to claim 37, Applicant urges that the amendments to this claim obviate the rejection. With regard to claim 39, Applicant urges that this claim is definite, as an ordinary artisan would understand the many over-the-counter or readily prescribed medications such as aspirin can be referred to as “small molecules,” and with regard to this claim, antibiotics are often administered to patients before dental works, which act as small molecule inhibitors of P. gingivalis.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to claim 37, the rationale for the modified indefiniteness rejection is set forth above.
With regard to claim 39, it appears that Applicant is urging that “small molecules” as present in claim 39 are intended to be aspirin and antibiotics. However, Applicant has provided no reference to what is intended to be included in, or excluded from, this term as provided in the specification. It is noted that there are a huge number of items that may be classified under the general term of “small molecules,” a large portion of which would not be appropriate for co-administration with P. gingivalis, and an inhibitor of P. gingivalis. It is suggested that Applicant instead claim the specific small molecule inhibitor(s) of P. gingivalis utilized in the invention as claimed and recited in the specification.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 25-31, 36-39, 41, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Wade et al. (US 2017/0199189, Published 2017 – Previously Presented), in view of Bassir et al. (Potential for Stem Cell-Based Periodontal Therapy, Journal of Cellular Physiology, Vol. 231, (2016), pp. 50-61 – Previously Presented), as evidenced by NCBI (Medication Routes of Administration, StatPearls, August 23, 2023, Available online at: www.ncbi.nlm.nih.gov/books/ NBK568677/#:~:text=Routes%20of%20Medication-,1.,by%20avoiding%20the%20 gastrointestinal%20tract).
With regard to claim 25, Wade et al. teach a method for assessing global wellness in a human patient through periodontal health and developing a maintenance/treatment program (Abs.; Fig. 1-7; Ex. 1-3). The method including assaying a body fluid sample including blood or saliva for an expression level of biomarkers (Abs.; Para. 17, 55, 158; Fig. 3, 4, 6); and obtaining a patient’s baseline periodontal status measurement including age, number and position of gum bleeding points upon probing, probing, which is determining tooth pocket depth, full mouth series digital radiograms, and intraoral camera photos (Abs.; Fig. 3, 4, 6; Para. 147; Ex. 1). According to the results of the assays and assessments, using these parameters, which is using a clinical calculator, to design a global wellness program/treatment plan for the subject (Abs.; Para. 19-21, 157, 216), which is determining the patient’s weighted score and using it to prescribe an individualized treatment plan. The goal of the treatment(s) in the treatment plan to result in, upon reassessment, a measurable improvement in the data points of the assays or assessments (Para. 22, 62, 216; Fig. 5-6).
While Wade et al. teach treatment of periodontal conditions to improve the patient’s multisystem health and wellness (Abs.; Fig. 1-7), it is not specifically taught that treatment includes intravenously injecting a therapeutically effective amount of a composition comprising multipotent stem cells into the patient’s oral vasculature.
Bassir et al. teach that periodontal diseases are highly prevalent and are linked to several systemic diseases, wherein periodontal treatment is challenging because the periodontium is complex, comprising different tissues, including bone, cementum, and periodontal ligament (Abs.). Stem cell therapies are an effective therapeutic tool for periodontal regeneration due to their plasticity and ability to regenerate different tissues (Abs.). The IV injection of an effective amount of bone marrow-derived skeletal stem cells (BMSSCs), which are multipotent stem cells, provided for new periodontium formation, and contributed to periodontal regeneration (Table 1).
It is not taught that the IV injection is done into specifically oral vasculature. However, IV injection is a systemic delivery system (see NCBI, p. 4, 1. Intravenous Route through p. 5 – IV injection provides direct administration of the injected substance to systemic circulation). As such, injection into any vein, including a vein in or around the mouth, would have been understood to be functionally equivalent to injection into any other vein, as IV injection necessarily provides for systemic delivery. Therefore, it would have been routine for an ordinary artisan to determine the desired IV injection site, including into oral vasculature, with a reasonable expectation that such delivery would provide for successful systemic delivery.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Wade et al. and Bassir et al., because both teach treatments effective for treating periodontal diseases, and that periodontal diseases are linked to systemic diseases. The IV injection of multipotent stem cells to treat periodontal diseases is known in the art as taught by Bassir et al. The treatment of periodontal diseases by IV injection of multipotent stem cells as taught by Bassir et al., amounts to the simple substitution of one known method of treating periodontal diseases to improve systemic health for another, and would have been expected to predictably and successfully provide an alternative treatment for periodontal diseases in the method of Wade et al.
Taken together, Wade et al. and Bassir et al. render obvious the method as claimed, including the components as claimed. As the method cannot be separated from its functions, performance of the method as rendered obvious would have necessarily provided the result of an improvement upon reassessment of at least 10% in at least one of the taught parameters.
With regard to claim 26, Wade et al. teach that the treatment plan includes one or more courses of medication, surgical treatments, and/or changes in behavior (Para. 69), wherein treatments include physical scaling, root planning, administration of systemic or local antibiotics, and laser therapy (169-170). As such, it would have been obvious to an ordinary artisan to utilize another treatment in addition to IV stem cell injection, including administration of an antibiotic. Wherein administration of the antibiotic would necessarily be concurrently or sequentially with the stem cell administration.
With regard to claim 27, Wade et al. teach that exemplary pathogens associated with disease and identified in oral DNA testing include Porphyromonas gingivalis (P.g.) (Para. 53), wherein treatments include administration of systemic or local antibiotics (169-170). As such, it would have been obvious to one of ordinary skill in the art to administer an antibiotic as a secondary treatment effective against P.g. when this bacterial species is identified in the patient under treatment.
With regard to claim 28, Wade et al. teach that the patient receives assessment, treatment, reevaluation, and follow-up care including at 6 weeks and 3 months (90 days) after an initial treatment (see Fig. 5, 6; Para. 255), and also that the treatment plan includes one or more courses of medication, surgical treatments, and/or changes in behavior (Para. 69), wherein treatments include physical scaling, root planning, administration of systemic or local antibiotics, and laser therapy (169-170). As such, it would have been obvious to an ordinary artisan that ongoing treatment would include periodontal cleaning and debridement (scaling) in the patient at 6 weeks and 3 months, which is within 90 days of the IV stem cell injection treatment of the combined method.
With regard to claim 29, Wade et al. teach that following the initial treatment, the assessment and periodontal status measurements are updated and compared to the baseline measurements, including with the use of a computer, where each parameter can be compared to an ideal value, and the treatment plan is revised if needed based upon the comparison (para. 155, 212, 415; Fig. 5, 6).
With regard to claim 30, Wade et al. teach that the treatment can be repeated as needed to provide the desired improvement, including at 3 months (90 days) (Fig. 5, 6; para. 255, 413). Wherein it would have been routine for an ordinary artisan to repeat steps of the combined method, including treatment by IV injection of the multipotent stem cells, until a desired improvement in measurements over the baseline is achieved, including every three months for one year.
With regard to claim 31, Wade et al. teach monitoring the improvement in the patient by updating measurements, wherein improvement is positive change in any parameter following treatment (Para. 218; Fig. 5-6).
With regard to claims 36-38 and 41, taken together, Wade et al. and Bassir et al. render obvious the method as claimed, including the components as claimed. As such, performance of the method of Wade et al. and Bassir et al. would necessarily provide the results of: stimulating dental bone regeneration, as measured by at least one of 2D or 3D x-rays, and providing a decrease in pocket depth; reducing the symptoms of bacterial infection, including P.g. infection; and treating an early symptom of Alzheimer’s disease or dementia, including cognitive dysfunction, memory loss, impaired speech, or a combination thereof, wherein the treatment provides for a 20% improvement in updated measurements over baseline measurements.
With regard to claim 39, Wade et al. teach that exemplary pathogens associated with disease and identified in oral DNA testing include P.g. (Para. 53), wherein treatments include administration of systemic or local antibiotics (169-170). As such, it would have been obvious to one of ordinary skill in the art to co-administer an antibiotic, which is deemed to be a small molecule inhibitor of P.g., when this bacterial species is identified in the patient under treatment.
With regard to claim 42, Wade et al. teach recording and storing the pretreatment baseline periodontal status measurements of the parameters and ideal values on a computer readable format; 6 weeks or 3 months (90 days) after the initial treatment, the parameters are re-measured; the stored pretreatment baseline periodontal status measurements and/or ideal values are retrieved from the computer readable format; the baseline and updated measurements and the ideal values are compared; and the comparison is used to determine an undated/second treatment plan (Fig. 5-6; Ex. 3; Para. 210-217). Taken together, Wade et al. and Bassir et al. render obvious the method as claimed, including the components as claimed. As such, performance of the method of Wade et al. and Bassir et al. would necessarily provide the results that the patient who follows the undated/second treatment plan achieves specific subgoals over the course of the undated/second treatment plan and progresses toward the ideal values until an at least 50% improvement is observed when the post-treatment measurements are compared to the pretreatment baseline periodontal status measurements.
Response to Arguments
Applicant urges that Bassir is directed to stem cell treatment of periodontal diseases, and only indicates that periodontal disease is linked to other systemic diseases generally. Additionally, neither Bassir nor Wade teach oral IV injection of stem cells, and it would not have been a routine or simple substitution to replace the standard tail vein injection for the more difficult oral IV injection. Further, Examiner’s finding that Wade and Bassir render obvious oral IV injection of stem cells as a direct route to treat systemic disease is based on impermissible hindsight.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s argument that Bassir is directed to stem cell treatment of periodontal diseases, and only indicates that periodontal disease is linked to other systemic diseases generally; in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here, Wade et al. teach that treatment of periodontal conditions improves a patient’s multisystem health and wellness (Abs.; Fig. 1-7), and Bassir et al. teach that stem cell therapies are an effective therapeutic tool for periodontal disease treatment (Abs.).
With regard to Applicant’s argument that neither Bassir nor Wade teach oral IV injection of stem cells, wherein it would not have been a routine or simple substitution to replace the standard tail vein injection for the more difficult oral IV injection, and the assertion that Examiner’s findings are based on impermissible hindsight; as noted, it is not taught that the IV injection is done into specifically oral vasculature. However, IV injection is a systemic delivery system (see NCBI, p. 4, 1. Intravenous Route through p. 5 – IV injection provides direct administration of the injected substance to systemic circulation). As such, injection into any vein, including a vein in or around the mouth, would have been understood to be functionally equivalent to injection into any other vein, as IV injection necessarily provides for systemic delivery. Therefore, it would have been routine for an ordinary artisan to determine the desired IV injection site, including into oral vasculature, with a reasonable expectation that such delivery would provide for successful systemic delivery. It does not appear that there would have been any difference in treatment function based on the vein utilized for the IV administration of the stem cells. An ordinary artisan would have understood that any usable vein necessarily provides direct introduction of the injected stem cells into the circulatory system for systemic delivery, thus treating periodontal conditions and improving the patient’s multisystem health and wellness.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Wade et al. teach that treatment of periodontal conditions improves a patient’s multisystem health and wellness (Abs.; Fig. 1-7), and Bassir et al. teach that stem cell therapies are an effective therapeutic tool for periodontal disease treatment (Abs.), and it would have been routine for an ordinary artisan to determine the desired IV injection site, including into oral vasculature, with a reasonable expectation that such delivery would provide for successful systemic delivery, as discussed previously.
New Rejections Necessitated by Amendment:
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 25 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Wade et al., in view of Bassir et al., as evidenced by NCBI, as applied to claim 25 above, and further in view of Albanese et al. (Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration, Immunity & Ageing, Vol. 10, Iss. 23, (2013), pp. 1-10).
The teachings of Wade et al. and Bassir et al. as applied to claim 25 have been set forth above.
With regard to claim 40, Bassir et al. further teach the administration of autologous stem cells (Table I). However, Wade et al. and Bassir et al. do not specifically teach the co-administration of autologous platelet-rich-plasma (PRP).
Albanese et al. teach that administration of autologous PRP with treatment of periodontal defects or periodontal surgery promotes tissue healing, while being minimally invasive (Abs.; p. 2, left col., para. 2).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Wade et al. and Bassir et al. with Albanese et al., because all teach treatments effective for treating periodontal diseases. The administration of autologous PRP with treatment of periodontal defects or periodontal surgery is known in the art as taught by Albanese et al. As such, an ordinary artisan would have been motivated to utilize co-treatment of periodontal conditions with autologous PRPs to better promote tissue healing. The further co-treatment of periodontal conditions using autologous PRP as taught by Albanese et al., in the combined method of Wade et al. and Bassir et al. would have been expected to predictably improve the method, because it is known that co-treatment with autologous PRPs when addressing periodontal conditions advantageously promotes tissue healing while being minimally invasive.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653