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 Status
Claims 11-13, 16, 18-23, 26, 27 and 31-35 are cancelled.
Claims 1-10, 14, 15, 17, 24, 25 and 28-30 are pending and under examination.
Withdrawn rejections
Applicant's amendments and arguments filed 6/25/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-10, 14, 15, 17, 24-25 and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Stasko (US20100098733) and Handa et al. (WO2019236825) and Cao et al. (Pharmaceutics 2020, 12, 926: 14 pages; of record) and Green (US20170304164).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a nitric oxide delivery research scientist who possesses interdisciplinary knowledge combining chemistry, materials science, and biology. That includes developing strategies to deliver nitric oxide in a controlled, sustained, and targeted manner to treat pathological conditions. Such an artisan has expert knowledge of compounds/materials that store and release nitric oxide including diazeniumdiolates and S-nitrosothiols as well as delivery vehicles for formulation with the NO donors. One can assume comfortably that such an educated artisan will draw conventional ideas from these areas— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claim 1, Stasko teaches an oral care composition comprising a nitric oxide releasing particle and an orally-acceptable carrier (Claims 1 and 14) where the nitric oxide donor is a nitrosothiol (Claims 3 and 16), which are S-nitrosothiol compounds, in the form of a gel (Claims 6 and 15) and comprising fluoride ion NaF (Claim 10).
Regarding claims 25 and 28-30, Stasko teaches methods of providing one or more oral health benefits to a subject comprising contacting an effective amount of an
oral care composition in an oral cavity of the subject, which provides treatment and/or prevention of infection caused by bacteria, viruses, fungi, yeast or herpes, dental carries, plaque formation and accumulation, gingivitis, periodontitis disease or other stomatognathic diseases (Claims 38-39). Delivering fluoride ions and nitric oxide to the oral cavity implicit as well as preventing or reducing the formation of biofilm is implicit in the method of Stasko.
Regarding claims 1, 9 and 14, Handa et al. teach the concept of compositions including a biocompatible material having a synthetic polymer combined with a natural polymer and the combined polymers are crosslinked with an antimicrobial effective amount of a NO-donor (Abstract; claim 1) where calcium chloride is added [0043, 0063], which provides calcium ions. Handa et al. teach that: “wherein the% weight/volume of the natural polymer is from about 0.1 % to 50%, the % weight/volume of the synthetic polymer is from about 0.1 % to 50%, and the NO-donor is from about 1 mg/ml to 50 mg/ml in a crosslinking solution.” (Claim 8). Handa et al. teach that the composition is used for drug delivery vehicles and antibacterial uses [0047] and expressly teach: “in addition to the base polymers that make the dressings, a therapeutic agent is included to prevent bacterial infection” [0054].
Regarding claims 6-8, Handa et al. teach that the natural polymer is sodium alginate (Claims 3 and 5). The same sodium alginate taught by Handa et al. will have the same viscosity as claimed. Also, disclosure of sodium would render obvious other alkali metal or alkaline earth metals to the ordinary artisan.
Regarding claim 1, Handa et al. teach that the NO-donor is S-nitrosoglutathione (Claim 6) as well as S-nitroso-N-acetylpenicillamine [0030] and other NO donors can be used [0041].
Regarding claim 24, Handa et al. teach hydrogel forms [0046-0047].
Regarding claims 1-5, 9-10, 14, and 24, Cao et al. teach the concept of nitric oxide releasing pluronic F127/alginate hydrogels with S-nitrosoglutathione (Abstract; Figures 1-3) with antibacterial activity (Figures 5-7; page 10, 3.5. In Vivo Wound Healing Activity). Cao et al. report that: “the GSNO-PL/AL treatment of MRPA-infected wounds accelerated healing and reduced the bacterial burden.” (Page 12, 4. Conclusions). Cao et al. teach: “The thermoresponsive hydrogel has an advantage over other GSNO-releasing hydrogels on GSNO stability, easy application, and controlled GSNO release.” (Page 2, 3rd paragraph). Compositions with 20% poloxamer and 1% alginate (w/v) are taught (Page 3, 2.3. page 5, 3.1.), which is a ratio of 20:1. Pluronic F127 meets the limitations of claims 2-4 (Instant specification [0050]). The amount of GSNO in the hydrogel was 1.9% (Page 6, 1st paragraph), which is 19 mg/mL.
Regarding claims 15, 25 and 28-30, Green teaches methods of improving oral health in a subject with S-nitrosothiols (Claims 1 and 4) and from 0.1 to 0.3% sodium fluoride (Claim 9) wherein improving oral health comprises reduction of dental plaque, gingivitis, oral infections, tooth decay, tooth loss, gum disease, oral cancer, throat cancer, oral sores, periodontal disease, gum disease, dental cavities, gingival recession and halitosis (Claim 13). Green teaches “Dental cavities can be prevented by maintaining a constant low level of fluoride in the oral cavity.” [0008]
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Stasko is that Stasko do not expressly teach a carrier composition for the nitrosothiol/sodium fluoride components comprising a poloxamer, alginate and calcium ions as instantly claimed for use in the methods of Stasko. This deficiency in Stasko is cured by the teachings of Handa et al. Cao et al. and Green.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the nitric oxide releasing nitrosothiol/NaF oral care composition of Stasko and use a carrier composition comprising a poloxamer, an alginate and calcium ions as claimed, as suggested by Handa et al. Cao et al. and Green, and employ the composition in the methods of Stasko to produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because of the following rationale. The test for obviousness is "what the combined teachings of the references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 4I3, 425 (CCPA I98I) (MPEP 2145(III)). In the present case, the combined references render obvious both the composition and methods claimed so that the ordinary artisan would achieve both with a reasonable expectation of success. The only limitation for the carrier of Stasko is that it is orally acceptable (Claim 1) and can be a gel (Claim 6). The combined references of Stasko, Handa et al., Cao et al. and Green render obvious a gel composition comprising a poloxamer, an alginate, a nitric oxide releasing compound (nitrosothiol), fluoride ions and calcium ions as instantly claimed. Especially when Handa et al. provide the concept of compositions including a biocompatible material having a synthetic polymer combined with a natural polymer and the combined polymers are crosslinked with an antimicrobial effective amount of a NO-donor S-nitrosoglutathione where cross-linking calcium chloride is added, which provides calcium ions, and Cao et al. provide concept of nitric oxide releasing pluronic F127/alginate hydrogels with S-nitrosoglutathione, where pluronic F127 is a synthetic polymer combined with the natural alginate polymer as taught by Handa et al., and bacterial burden is reduced. Every dependent limitation is met by the combined references as discussed above. Selection of any of the known conventional nitrosothiol NO-donor compounds or combination thereof is obvious to the ordinary artisan in this art. One of ordinary skill in the art would do so with a reasonable expectation of success. Claim 17 is a product-by-process claim. Please note that in product-by-process claims, “once a product appearing to be substantially identical is found and a 35 U.S.C. 102/103 rejection [is] made, the burden shifts to the applicant to show an unobvious difference.” See MPEP 2113 Product-by-Process Claims [R-08.2017]
I. PRODUCT-BY-PROCESS CLAIMS ARE NOT LIMITED TO THE MANIPULATIONS OF THE RECITED STEPS, ONLY THE STRUCTURE IMPLIED BY THE STEPS
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). The composition of claim 17 is consequently obvious over the combined references.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments filed 6/25/26 have been carefully considered but are not persuasive.
On page 5 of remarks, Applicant asserts that “consisting of” in claim 1 has closed the composite material to the addition of other elements or ingredients not specified in the claim. Applicant states: “The composition recited in claim 1 only includes the nitric oxide releasing compounds recited in the claim and no other additional components or elements. Although claim 1 recites the term "comprising" with respect to the composition, the nitric oxide releasing compound is limited to only those recited in the claim.” The Examiner does not dispute this.
On pages 7-8 of remarks, Applicant argues that Stasko teaches an exemplary preparation with a nitric-oxide releasing silica particle. Applicant contends that the nitric oxide releasing particles disclosed in Stasko do not fall under the nitric oxide releasing compounds recited in claim 1 in view of the transitional phrase “consisting of”. Applicant also argues that the skilled artisan would not substitute the nitric oxide releasing particles with the other nitric oxide releasing compounds as there is no teaching or suggestion in Stasko to do so. Respectfully, the Examiner has a different perspective. Stasko unambiguously claims nitrosothiols, as well as diazeniumdiolate, nitrosamine, hydroxyl nitrosamine, hydroxyl amine, hydroxyurea and combinations thereof, as the nitric oxide donor in the nitric oxide releasing particles (Claims 1, 3, 14 and 16). As stated by Stasko: “As used herein, the terms "nitric oxide donor" or "NO donor" refer to species that donate, generate, release, and/or directly or indirectly transfer a nitric oxide species, and/or stimulate the endogenous production of nitric oxide in vivo and/or elevate endogenous levels of nitric oxide in vivo such that the biological activity of the nitric oxide species is expressed at the intended site of action.” [0050] Accordingly, these nitric oxide donors are considered functional equivalents for their intended purpose. In other embodiments, the nitric oxide donor is formed from an aminoalkoxysilane by a pre-charging method such that diazeniumdiolated aminoalkoxysilane is formed (Claims 4-5). The Examiner has not applied the diazeniumdiolated aminoalkoxysilane embodiments of Stasko. Rather, the Examiner has focused on Stasko teaching nitrosothiols for the nitric oxide releasing compound. Instant claim 1 does not exclude carrier particles for the nitric oxide releasing compound but is only limited to the chemical nature of the nitric oxide releasing compound, which are species of conventional nitrosothiols taught by the secondary references. Applicant did not invent the claimed nitrosothiols.1 Consequently, Stasko render equivalent the nitrosothiols in the nitric-oxide releasing particles and the ordinary artisan is guided to using conventional nitrosothiols known in the art and would have a reasonable expectation of using nitrosothiols in the particles of Stasko. It is then merely judicious selection of known nitrosothiols in the art by the ordinary artisan. See MPEP 2144.07: “The selection of a known material based on its suit ability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)”. Also from Sinclair & Carroll Co. V. Interchemical Corp.: ““Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle.” (325 U.S. at 335, 65 USPQ at 301.). Moreover, “Where two known alternatives are interchangeable for a desired function, an express suggestion to substitute one for the other is not needed to render a substitution obvious." In re Fout 675 F.2d 297, 301 (CCPA 1982). Stasko discloses nitrosothiols as a functional nitric oxide donor alternative and the secondary references guide the artisan to species within that genus. It requires no inventive effort to employ those species. Respectfully, Applicant’s arguments are not persuasive.
The test for obviousness is "what the combined teachings of the references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 4I3, 425 (CCPA I98I) (MPEP 2145(III)). In the present case, the combined references render obvious the claimed composition. No unexpected results have been shown or argued. Therefore, the claimed composition is obvious in view of the combined references without more.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 The claimed nitrosothiol species are well-known in the art. See for example [0012] of Handa et al. (US20190039910) teaching: “S-nitrosothiol such as S-nitroso-N-acetyl-penicillamine, S-nitroso-N-acetyl cysteine, S-nitroso-N-acetyl cysteamine, S-nitrosoglutathione, methyl S-nitrosothioglycolate, or a derivative thereof.”
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