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 .
Claim(s) 7, 10, 13, 16 and 19-26 are currently pending.
Claim Objections
Claim 16 objected to because of the following informalities:
In claim 16, “decreasing a gingipain” should read “decreasing gingipain”
Appropriate correction is required.
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.
Claim(s) 10 and 22-24 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.
Claim(s) 10 and 22-24 are indefinite because it is unclear what diseases are considered to be “associated” with Porphyromonas gingivalis. Page 9 of the specification gives a non-limiting definition of what is considered to be “associated” with Porphyromonas gingivalis. Furthermore, claim(s) 22-24 depend from claim 10 and do not clarify the issue. Thus, the metes and bounds of the claim are unclear.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 7, 10, 13, 16, 19-26 are rejected under 35 U.S.C. 103 as being unpatentable over Kawada (JP 2003171292 A – English translation provided) in view of Kim (KR 20190041864 A – English translation provided) and Chen (Muscosal Immunology, (Year: 2017), vol. 10, pp. 215-227).
Kawada teaches periodontal disease-causing bacteria to be exterminated [to] include, for example, Porphyromonas gingivalis (PG bacterium) (page 4). Kawada teaches the preventive or therapeutic agent for periodontal disease of the present invention is characterized by containing bacteria belonging to Bifidobacteria, lactic acid bacteria or butyric acid bacteria, and the bacteria can be Streptococcus (Enterococcus) faecalis and further contains saccharides (pages 3-4). Kawada teaches periodontal disease-causing bacteria, [such as gingipains] (page 3). Kawada teaches that the E. faecalis can suppress the growth of the bacteria (e.g. Porphyromonas gingivalis) (page 3). Kawada teaches [that] Porphyromonas gingivalis (hereinafter abbreviated as PG bacterium) which is a periodontal disease bacterium (pages 8-9).
Kawada does not teach the methods for the prevention and/or treatment of Porphyromonas gingivalis infection, comprising administering to a subject a pharmaceutically effective amount of killed E. faecalis, the killed E. faecalis is mixed with a carrier, and the carrier excludes sugar (as stated within claim 7 of the present invention). Kawada does not teach a method for prevention and/or treatment of a Porphyromonas gingivalis-associated disease, comprising administering to a subject a pharmaceutically effective amount of killed E. faecalis (as stated within claim 10 of the present invention).
Kawada does not teach a method for decreasing the growth of Porphyromonas gingivalis in a subject in need thereof, comprising administering to a subject a pharmaceutically effective amount of killed E. faecalis, the killed E. faecalis is mixed with a carrier, and the carrier excludes sugar (as stated within claim 13 of the present invention). Kawada does not teach a method for decreasing a gingipain activity in a subject in need thereof, comprising administering to a subject a pharmaceutically effective amount of killed E. faecalis, the killed E. faecalis is mixed with a carrier, and the carrier excludes sugar (as stated within claim 16 of the present invention). Kawada does not teach that an administration dose of the amount of killed E. faecalis is 108-109 CFU/kg body weight (as stated within claim(s) 19, 23 and 25-26 of the present invention). Kawada does not teach that the Porphyromonas gingivalis-associated disease comprises at least one selected from the group consisting of cardiovascular diseases, endocarditis, coronary heart disease, pneumonia, preterm birth and low birth weight, atherosclerosis, dementia, Alzheimer's disease, obesity, non-alcoholic steatohepatitis (NASH), diabetes, frailty, and sarcopenia (as stated within claim 21 of the present invention). Kawada does not teach that the method according to claim 10, wherein the method decreases the growth of P. gingivalis (as stated within claim 22 of the present invention). Kawada does not teach that the killed E. faecalis is mixed with a carrier, and the carrier excludes sugar (as stated with claim 24 of the present invention).
Kim teaches a composition for preventing or treating periodontitis ([a disease that is mentioned in page 9 in the specification of the present invention]) using heat-treated Enterococcus faecalis (page 4). Kim teaches a composition for preventing or treating an inflammatory disease comprising Enterococcus faecalis (pages 1-2). Kim teaches [that] excessive acute or chronic inflammation, however, can cause serious disorders such as Parkinson's disease, Alzheimer's disease (page 2). Kim teaches [that] in the present invention, the inflammatory disease is selected from the group consisting of periodontitis (page 5). Kim teaches [that] the carrier and the additive may be any pharmaceutically acceptable ones. Specific examples of the diluent include cornstarch, Microcrystalline cellulose (page 4). Kim teaches [that] the composition of the present invention may contain the strain as an active ingredient in an amount of 10 .sup.6 to 10 .sup.13 cfu / g, based on the total weight of the composition, or may include culture or dead cells having an equivalent number of live cells (page 4). Kim teaches [that] the pharmaceutical compositions of the present invention may be administered to a patient in a single dose and may be administered by a fractionated treatment protocol in which multiple doses are administered over a prolonged period of time (page 5). Kim teaches [that] the pharmaceutically effective amount may be appropriately changed according to various factors such as the disease and its severity, the patient's age, body weight (page 5).
Chen et al teaches that heat-killed E. faecalis is a widely used probiotic (abstract), Chen et al also teaches that heat-killed probiotics are safer than live probiotics for purposes such as eliminating antibiotic-resistant genes, preventing production of recombinant strains, controlling the microbial load during probiotic supplementation, and application in children and immunosuppressed patients (page 215).
The method as taught by Kawada can be modified to include the knowledge that P. gingivalis secretes gingipains ([that can cause an infection]), that the bacterium (e.g. P. gingivalis) is involved in the pathogenicity of [a disease, like periodontitis], and that a preventative or therapeutic agent for periodontal disease can be E. faecalis, all taught by Kawada. In addition, Kawada's method can be modified to include information that heat-treated E. faecalis is used for preventing or treating periodontitis (an inflammatory disease) as taught by Kim along with additional knowledge that heat-treated E. faecalis has antibiotic elimination capabilities and the ability to help immunosuppressed individuals in which, Parkinsons and Alzheimers disease (e.g. both are two types of dementia) can come about as a result of acute or chronic inflammation (e.g. periodontitis). Moreover, the method as taught by Kawada can be modified to further include that instead of a sugar carrier that must be attached, a carrier like corn starch or microcrystalline cellulose as taught by Kim can be used as a replacement carrier.
One would reasonably expect that the aforementioned references combined do explicitly teach that heat-treated and non heat-treated E. faecalis that is bonded with a sugar or a non-sugar carrier has the capability of treating an infection, exhibits a decrease in growth of gingipain activity or the growth of bacteria all attributed to P. gingivalis with an explanation of the advantageous effects of using the heat-treated E. faecalis bacterium. One of ordinary skill in the art would reasonably expect that the combination of references would effectively accomplish the overall goal of the claimed invention: to treat P. gingivalis using a pharmaceutically effective amount of a killed strain of E. faecalis to treat or reduce the presence of P. gingivalis activity, which may lead to a reduction of occurrence of infections ([which may prevent the progression of a disease]), and may also lead to a reduction of growth and virulence growth factors attributed the P. gingivalis bacterium. In addition, one of ordinary skill in the art would expect to administer an effective amount of heat-killed E. faecalis necessary to achieve the reduction and/or amelioration of P. gingivalis activity.
Regarding claim(s) 19, 23 and 25-26, the combined aforementioned reference does not explicitly teach the administration dose per cfu/kg body weight in the amounts claimed by the applicant. However, as discussed in MPEP section 2144.05(II)(A), “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).” The references teach the use of each of the ingredients in a pharmaceutical composition. Varying the concentration of ingredients within a pharmaceutical composition is not considered to be inventive unless the concentration is demonstrated as critical. In this particular case, there is no evidence that the claimed concentration of the ingredients produces an unexpected result. Thus, absent some demonstration of unexpected results from the claimed parameter, this optimization of ingredient concentration would have been obvious before the effective filing date of applicant’s claimed invention. One of ordinary skill in the art would reasonably expect to optimize the dosages of heat-killed E. faecalis that contains a non-sugar carrier necessary to be administered to a subject in need for prevention and/or treatment of P. gingivalis infection, prevention and/or treatment of a P. gingivalis-associated disease such as Parkinsons or Alzheimers disease (a type of dementia), for decreasing gingipain activity and for decreasing the growth of P. gingivalis.
Response to Arguments
Applicant’s arguments filed April 14, 2026 have been fully considered, and the arguments regarding the rejection under 35 U.S.C. 103 are found to be non-persuasive. Regarding applicant’s remarks for the 35 U.S.C. 103 rejection wherein obviousness by Kawada, Kim and Chen et al for claim(s) 7, 10, 13 and 16 fails to teach or suggest each and every element of the claims. Beginning on page 4 of applicant arguments, applicant states “the combination of the cited references fails to teach or suggest any killed E. faecalis which is mixed with a carrier excluding sugar as set forth in the present claims”, “from reading Kawada, one of ordinary skill in the art would have no reason to modify Kawada’s composition to exclude sugar” and that “Kawada does not teach or suggest any of Porphyromonas gingivalis-associated disease, especially those claimed in new claim 21. In addition, the remaining references fail to cure this deficiency of Kawada. Accordingly, the combination of the cited references fails to teach or suggest each and every element of the claims”. Although Kawada does not explicitly teach that the composition at hand has a heat-treated E. faecalis, does not teach that the composition excludes sugar and does not teach any of P. gingivalis-associated diseases, the Kim reference effectively remedies those deficiencies in order to state that a starch, like corn starch or microcrystalline cellulose can be a carrier. In addition, the Kim reference also discusses that heat-treated E. faecalis has antibiotic elimination capabilities and the ability to help immunosuppressed individuals in which, Parkinsons and Alzheimers disease (types of dementia) can come about as a result of acute or chronic inflammation (e.g. periodontitis which is known to be caused by P. gingivalis – already stated by Kawada). Thus, using a heat-treated form of E. faecalis bonded with a non-sugar carrier would also be sufficient in treating a P. gingivalis-associated disease like Alzheimer’s disease. Moreover, the use of the Chen et al reference further reinforces the fact that heat-killed E. faecalis is a widely used probiotic especially for treating immunosuppressed patient populations, thus, the combination of all of the aforementioned references is sufficient to not only remedy the deficiencies of the Kawada reference but are also sufficient for overcoming the amended claims of the present invention. In addition, based on the newly added claims of the present invention, more specifically, claim(s) 19-26, the combined aforementioned references are also successful in overcoming the newly added claims. It is also important to note that although the combined aforementioned references do not teach the administration dose of the amount of killed E. faecalis is 108-109 CFU/kg body weight, as discussed in MPEP section 2144.05(II)(A), “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).” The references teach the use of each of the ingredients in a pharmaceutical composition. Varying the concentration of ingredients within a pharmaceutical composition is not considered to be inventive unless the concentration is demonstrated as critical. In this particular case, there is no evidence that the claimed concentration of the ingredients produces an unexpected result. Thus, absent some demonstration of unexpected results from the claimed parameter, this optimization of ingredient concentration would have been obvious before the effective filing date of applicant’s claimed invention. Thus, one skilled within the field of microbiology and molecular biology would find that the combination of all of the aforementioned references overcomes the present inventions amendments and the newly added claims and thus, the rejection under 35 U.S.C. 103 is maintained.
No claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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NASHARA L MOREAU
Examiner, Art Unit 1655
/SUSAN HOFFMAN/Primary Examiner, Art Unit 1655
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