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 .
Claims 1-2,5-6,13-18, and 21 are under examination.
Response to Applicants Arguments/Amendments
The arguments involving the 103 rejection are addressed under the prior art rejection. The double patenting rejection is withdrawn because of the terminal disclaimer filed on 4/16/2016.
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.
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.
Claims 1-2,5-6,13-18, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Cella (WO 2018165765) in view of Lee (WO 2022050797), Sanguansermsri et al. “Interspecies dynamics among bacteria associated with canine periodontal disease” Molecular Oral Microbiology, 33(1), 59-67 (2018), and Sheng-Wei (CN 106361683). Lee US 20230381093 can be used as an English translation for WO 2022050797. The references are already of record.
Cella teaches a method of minimizing oral bacterial infection and/or minimizing bacterial biofilm forming infection in a subject in need thereof, the method comprising orally administering to the subject a nutritional supplement or food product comprising a bacterial cell free fermentate (also known as a cell free supernatant) mixture containing peptides effective against biofilms. (Pages 2- 3, 9-11). Page 9 states that the bacteria supernatant/fermentate can be derived from one or more of the bacteria listed which also include Bacillus subtilis and Pediococcus pentosaceus (Page 9). Cella teaches that such supernatants can treat the Neisseria pathogen (Page 19).
It would have been obvious to have combined only the cell free supernatants/cell free fermentates from Bacillus subtilis and Pediococcus pentosaceus since both supernatants can both produce molecules/peptides that can inhibit unwanted pathogens and prevent/treat unwanted biofilm formation (Abstract and Pages 2,3, and 9 of Cella). MPEP 2144.06 recites "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). Therefore, it would have been obvious to have combined the cell free supernatant from a Bacillus subtilis fermentation culture with a cell free supernatant from a Pediococcus pentosaceus fermentation culture to treat oral infections. Cella teaches that such a composition can be administered to dogs and/or cats (Page 7).
Cella does not provide a specific Bacillus subtilis species fermentate that is able to destroy/disrupt oral biofilms which cause halitosis/bad breathe. However, Lee teaches that the Bacillus subtilis ID-A05 strain fermentate can be used to treat cavities, periodontal disease, and halitosis and disrupt unwanted biofilms (Abstract, Examples 6, and Examples 10). Lee teaches that the Bacillus subtilis ID-A05 strain reduces the ability of strains to form a biofilm and substantially grow (Examples 6-7). Furthermore, Example 10 of Lee shows that treatment with Bacillus subtilis ID-A05 strain fermentate reduced the occurrence of VSCs produced by organisms such as Fusobacterium nucleatum It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the Bacillus subtilis ID-A05 strain supernatant/fermentate because it is able to effectively disrupt biofilm formation and reduce the production of VSCs (Examples 6-7 and 10). Because the evidence of Lee shows that the fermentate from Bacillus subtilis ID-A05 can successfully disrupt biofilm formation, there would have been a high expectation for success using Lee’s specific fermentate to destroy the oral biofilm.
Cella teaches that its fermentate can be used to treat Neisseria and/or its biofilms in the oral cavity but fails to identify a specific species of Neisseria. However, Sanguansermsri teaches that the main type of Neisseria pathogen that causes halitosis is Neisseria canis (Summary of Sanguansermsri, Pages 1-4). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used Cella’s fermentate composition to treat Neisseria canis . An artisan would have been motivated to have used Cella’s fermentate to treat halitosis resulting from the presence of Neisseria canis because Sanguansermsri teaches that Neisseria canis is one of the main causative agents of halitosis and periodontal diseases (Pages 1-4 of Sanguansermsri). Furthermore, Cella teaches that its cell free fermentate can successfully target Neisseria species (Page 7). There would have been a high expectation for success since Cella teaches that its fermentates can be used to treat Neisseria and target the oral biofilms that would inherently contain the Neisseria canis (Abstract and Pages 2,3, 9, and 19 of Cella) as in instant Claims 1-2, 5-6, 13-14,18 and 21
Cella does not teach how its composition affects levels of volatile sulfur compounds, including VSCs produced by Fuscobacterium nucleatum during an episode of halitosis. However, the elimination of VSCs by fermentates are taught in other references. Sanguansermsri teaches that Fuscobacterium nucleatum and P. gingivalis are prominent secondary colonizers of the biofilms which are responsible for VSCs/halitosis(Page 4 of Sanguansermsri). Neisseria canis can also be found in the oral/dental biofilms (Page 2 of Sanguansermsri). Cella teaches that strains such as Pediococcus pentosaceus can be successfully used to Pages 2- 3, 9-11 disrupt biofilms. If biofilms are disrupted, they will not be able to harbor halitosis causing organisms for long periods of time which are capable of producing VSCs. Without the halitosis causing organisms due to the eventual breakdown of the biofilms, the VSCs level would decrease. This phenomenon is taught by Lee. Lee teaches a fermentate that is able to disrupt biofilm formation (Examples 6-7). Lee also teaches that its fermentate causes a significant decrease in VSC levels (Example 10). This shows that that a strain that is able to disrupt a biofilm is also able to decrease VSC levels (Example 10 of Lee). Sheng Wei states that Pediococcus pentosaceus fermentate can be used to treat halitosis characterized by increased levels of volatile sulfur compounds.
Cella teaches that Pediococcus pentosaceus cell free supernatant can be used to successfully disrupt/destroy biofilms which would help to remove unwanted halitosis causing organisms from the oral cavity. Since Cella teaches that Pediococcus pentosaceus can break apart biofilms, the destruction of biofilms would lead to a reduction in VSCs produced by such strains as Fuscobacterium nucleatum.
Lee further states that disrupting biofilms is associated with a decrease in VSCs produced by halitosis biofilm colonizers such as Fuscobacterium nucleatum. Furthermore, Sheng-Wei specifically teaches that Pediococcus pentosaceus can be used in a composition to treat halitosis (associated with an occurrence of unwanted VSCs) which would be produced by mainly Fusobacterium nucleatum and P. gingivalis as taught in Page 4 of Sanguansermsri. Thus, it would be obvious that the Pediococcus pentosaceus would be capable of reducing the occurrence of volatile sulfur compounds (VSCs) produced by organisms including Fusobacterium nucleatum. The Pediococcus pentosaceus fermentate and Bacillus subtilis fermentate are capable of breaking apart biofilms which would remove VSC producing microbes from the oral cavity and these organisms would have less time to produce VSCs within the biofilm, thus lowering the VSC levels. Reducing components of the biofilm (composed of bacteria) and the duration of time the biofilm exists, would decrease the amount of VSC levels produced by the bacteria left alive. Furthermore, administering the supernatants would cause the eventual failure of the biofilm, limiting the amount of time each living bacteria (including Fusobacterium nucleatum) had in the biofilm to produce VSCs.
Dependent Claims taught by Cella
Cell teaches that compositions comprising the therapeutic molecules described herein may comprises about 0.00001% to about 99% by weight of the active agent and any range therein between (Page 13, 2nd paragraph). Cella further states that an overall dose of the composition can be 300 mg (Page 13, 2nd paragraph) as in instant Claims 15-16. Page 10 states that the “molecules can be incorporated into a variety of substances for administration to a subject such as any type of animal and humans. For example, the molecules can be incorporated into any type of food product, nutritional supplement, or beverage for animal or human consumption (Page 10 of Cella) as in instant Claim 17.
Cella teaches the required cell free-supernatants/cell-free fermentates can be successfully used to treat oral infections such as halitosis by breaking apart the biofilms where the harmful halitosis microbes reside. An artisan would have been further motivated to have used the specific Bacillus subtilis fermentate composition of Lee since it can break down biofilm and reduce the expression of volatile sulfur compounds which cause halitosis. Sanguansermsri is applied to teach that both Fusobacterium nucleatum and Neisseria canis are located in the same region/same biofilm/same oral cavity. Sheng-Wei teaches that Pediococcus pentosaceus can be used in a composition to treat halitosis; halitosis is characterized by an increase in VSCs. It would be expected for Sheng-Wei’s treatment to reduce VSC levels once administered. These references teach that Bacillus subtilis and Pediococcus pentosaceus fermentates can not only disrupt biofilms but these fermentates can also reduce the level of VSCs. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and microbiology. Therefore, the level of ordinary skill in this art is high.
Response to Applicants Amendments/Argument
Applicants have added the limitation, “reducing the extent to which a live bacterium belonging to the species Fusobacterium nucleatum can increase the concentration of volatile sulfur compounds (VSCs) in a canine oral microenvironment while present in the canine oral microenvironment.”
This amendment does not distinguish the claim from the prior art. As discussed in the rejections, it is known that the supernatants/fermentates can disrupt biofilms. If such agents (the fermentates) are administered, they will cause the destruction of the biofilm, limiting the time the live bacteria within in the biofilm have to produce volatile sulfur components. This reduction in time will directly result in a decrease in production of volatile sulfur components by live bacteria including Fusobacterium nucleatum.
Applicants argue that the prior art references cited in the past rejections, “fail to discriminate between destruction of biofilms (removing bacteria from environment) and directly reducing the extent to which live bacteria present in an environment and which recolonize after prior biofilm disruption can increase VSC concentrations therein.”
This argument is not commensurate in scope with the instant set of claims. The claim limitations do not recite that the biofilm in which the bacteria reside is first disrupted and then the bacteria recolonize and produce decreased amounts of volatile sulfur compounds. Furthermore, disrupting a biofilm with fermentate/supernatant treatments would reduce the number of the biofilm’s bacteria capable of producing volatile sulfur compounds and also reduce the time the average bacteria within the biofilm has to produce volatile sulfur compounds. Therefore, it would have been expected that adding agents to destroy/harm the biofilm would also result in a decreased production of volatile sulfur compounds by biofilm bacteria.
Applicants argue that the examiner states that “Sheng Wei states that pediococcus pentosaceus fermentate can be used to treat halitosis. A characteristic of halitosis is the increased levels of volatile sulfur compounds” and not a decrease. The examiner meant that halitosis is characterized by an increase in volatile sulfur compounds before treatment.
Both Sheng Wei and Cella teach that their treatments that can improve halitosis. Cella teaches that fermentates from Pediococcus pentosaceus and Bacillus subtilis can help break apart biofilms. Lee also teaches that its strain of Bacillus subtilis can help break down/break apart biofilms. If biofilms break apart, that will decrease the number of F. nucleatum organisms present in the oral cavity and decrease the amount of time these bacteria have to produce volatile sulfur compounds.
Conclusion
All claims stand 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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