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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/09/2026 has been entered.
Applicants' arguments, filed 06/09/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112—New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 has been amended to recite “a conjugation efficiency of at least 70%”. This amendment constitutes new matter insofar as it was not supported by the disclosure as originally filed.
The instant specification states, “The conjugation efficiency ranged from 45 to 79%” (p. 38, lines 5-6), with Table 2 (p. 38), shown below, for support of the range:
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398
1154
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(p. 38).
As shown above, the maximum percentage for conjugation efficiency of CafA was 79%. Because the claimed amendment, i.e., “at least 70%”, has no upper limit, it causes the claim to read on conjugation efficiencies above 79%, where there is no support.
Similarly, in the decision of In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976), the ranges described in the original specification included a range of "25%- 60%" and specific examples of "36%" and "50%." A corresponding new claim limitation to "at least 35%" did not meet the description requirement because the phrase "at least" had no upper limit and caused the claim to read literally on embodiments outside the "25% to 60%" range, however a limitation to "between 35% and 60%" did meet the description requirement (see MPEP 2163.05).
Claim Rejections - 35 USC § 102/103—New by Amendment
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
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.
Claim(s) 1, 5 and 17 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Desai (Electronic Thesis: University of Louiville, May 2020).
Desai teaches, “Functionalized nanoparticles with CafA protein to target BAR peptide for oral applications” (Ti).
“To enhance the efficacy of BAR peptide (IC50=1.3µM), we developed polymeric poly (lactic-co-glycolic acid) (PGLA) nanoparticles (NPs) encapsulating BAR (BAR-NPs)”, which can inhibit “P. gingivalis – S. Gordonii biofilm formation more potently relative to free peptide” (p. 32, 2nd paragraph).
The NP’s were synthesized using an oil-in-water technique wherein, “polyvinyl alcohol (PVA)” was included in the solution with PLGA and CafA (p. 41, 2nd paragraph).
Accordingly, the NP’s comprised a hydrophobic polymer, PLGA, as well as a hydrophilic polymer, PVA, as per claims 2-4.
BAR is taught to have the following sequence: NH2-LEAAPKKVQDLLKKANITVKGAFQLFS-COOH (p. 38, Peptide Synthesis), as per claim 17.
The conjugation efficiency of CafA onto the nanoparticles “ranged from 45 to 79%” (p. 53, 1st paragraph), having a supporting Table 2 below:
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(p. 54).
In regard to claim 5 Desai teaches, “The average unhydrated diameters of CaFA-modified BAR NPs and unmodified BAR NPs measured from SEM images were 89.7±26.3 and 165.8±33.4 nm, respectively” (p. 51). Here, 89.7±26.3 falls within claimed range of about 50 nm to about 100 nm.
The prior art is anticipatory insofar as it teaches a composition comprising a BAR polypeptide encapsulated within a nanoparticle, where the nanoparticle is comprised of at least one hydrophobic, i.e. poly lactic acid, wherein the nanoparticle further comprises CaFA polypeptides attached thereto at a concentration efficiency of at least 70%. Assuming, purely arguendo, that the teaching is not specific enough to rise to the level of anticipation, it would have been obvious to a person having ordinary skill to make a composition comprising a BAR polypeptide encapsulated within a nanoparticle having attached thereto CafA for the purpose of inhibiting pre-formed P.gingivalis/ S. gordonii biofilm, in view of Desai.
Claim Rejections - 35 USC § 102/103--Previous
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
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.
Claim(s) 1 and 17 remain rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Krishnan (Electronic Theses and Dissertations, 2018).
Krishnan teaches, “targeted BAR encapsulated poly(lactic-co-glycolic acid; PLGA) nanoparticles (NPs) to increase the efficacy of BAR to inhibit P. gingivalis colonization in a dual species biofilm” (p. vi).
“NPs encapsulating BAR peptide potently inhibited pre-formed P.gingivalis/ S. gordonii biofilm. These results suggest that enhanced inhibition of P. gingivalis was be [sic] obtained with BAR-NPs, identifying a novel therapeutic approach to effectively targeting P. gingivalis colonization of the oral cavity” (p. vii).
The NP’s were synthesized using an oil-in-water technique wherein, “polyvinyl alcohol (PVA)” was included in the emulsion (p. 18, 1st full paragraph).
Accordingly, the NP’s comprised a hydrophobic polymer, PLGA, as well as a hydrophilic polymer, PVA, as per claims 2-4.
BAR is taught to have the following sequence: BAR NH2-LEAAPKKVQDLLKKANITVKGAFQLFS-OH (p. 14, Table 1), as per claim 17.
In regard to CafA Krishnan teaches, “In addition to specifically targeted delivery to particular niches (here in the oral cavity), surface modification may decrease the initial release of encapsulant from the NPs, aiding in prolonged release” (p. 11, 1st paragraph). “To achieve this, we envision the use of CafA adhesin. CafA or coaggregation factor A is on of the 14 cell surface proteins of Actinomyces oris that posses the LPXTG anchoring motif that is recognized by sortase . . . Surface modifications of NPs with CafA represents an approach to target NPs or fibers to streptococcal cells, a primary initial niche of P. gingivalis in the oral cavity” (Id.)
In regard to conjugation efficacy Krishnan teaches, “the level of surface associated CafA will be adjusted to increase or decrease the retention on streptococci” (p. 42, 3rd paragraph). Accordingly, "[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" (see MPEP 2144.05 IIA quoting In re Aller, 220 F.2d 454, 456 (105 USPQ 233)).
The prior art is anticipatory insofar as it teaches a composition comprising a BAR polypeptide encapsulated within a nanoparticle, where the nanoparticle is comprised of at least one hydrophobic, i.e. poly lactic acid, wherein the nanoparticle further comprises CaFA polypeptides attached thereto at a concentration efficiency suitable to increase or decrease the retention on streptococci. Assuming, purely arguendo, that the teaching is not specific enough to rise to the level of anticipation, it would have been obvious to a person having ordinary skill to make a composition comprising a BAR polypeptide encapsulated within a nanoparticle and CafA polypeptides attached thereto for the purpose of inhibiting pre-formed P.gingivalis/ S. gordonii biofilm, in view of Krishnan.
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.
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.
Previous
1) Claim(s) 5 remains rejected under 35 U.S.C. 103 as being unpatentable over Krishnan (Electronic Theses and Dissertations, 2018) as applied to claim 1 above, and further in view of Teulon et al., (nanomaterials, December 2018).
Krishnan, which is taught above, differs from claim 5 insofar as it does not teach an average diameter range for the nanoparticles.
Teulon et al. teaches, “Nanoparticles are defined as elementary particles with a size between 1 and 100 nm for at least 50% (in number) (Abstract).
“Despite differences in international definitions on nanoparticles (NPs) especially concerning solubility, aggregation, and distribution threshold, current regulatory agencies consider that a primary nanomaterial is a nanoparticle (NP) when at least one of its dimensions is in the range 1–100 nm [1], values below the diffraction-limited resolution of conventional microscopy. In Europe, the 2011/696/EU commission recommendation states that a product containing primary particles for 50% or more of the particles in the number size distribution and one or more external dimension in the size range 1–100 nm is a nanomaterial” (p. 2, Introduction, 1st para.).
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to adhere to current regulatory agency standards of what constitutes a nanoparticle by providing the nanoparticles of Krishnan with an average particle size in the range of 1-100 nm.
Since the prior art size restriction is based on toxicology, i.e., “particle toxicology generally assumes that an increase in particle surface leads to increase in toxicity” (p. 2, Introduction, 2nd paragraph), it would behoove the artisan to adhere to regulatory standard to avoid causing harm to the patient. Accordingly, it would have been obvious to a person having ordinary skill in the art at the time of applicant’s invention to provide the nanoparticles of Krishnan within the claimed range of about 50-100 nm.
New by Amendment
2) Claim(s) 1, 5 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Krishnan (Electronic Theses and Dissertations, 2018) in view of Akagi et al., (Polymer, 2007) and Desai (Electronic Thesis: University of Louiville, May 2020).
Krishnan teaches, “For drug delivery, it is often desirable for NPs [nanoparticles] to release the drug upon reaching the appropriate sites and hence, biodegradable formulations can aid in this endeavor. Poly(lactic acid, PLA), poly(lactic-co-glycolic acid, PLGA), polycaprolactone (PLCL) are different biodegradable formulations that have been used for nanoparticle synthesis” (p. 9, 1st paragraph)
Krishnan teaches a specific embodiment of a nanoparticle drug carrier, i.e., “targeted BAR encapsulated poly(lactic-co-glycolic acid; PLGA) nanoparticles (NPs) to increase the efficacy of BAR to inhibit P. gingivalis colonization in a dual species biofilm” (p. vi).
“NPs encapsulating BAR peptide potently inhibited pre-formed P.gingivalis/ S. gordonii biofilm. These results suggest that enhanced inhibition of P. gingivalis was be [sic] obtained with BAR-NPs, identifying a novel therapeutic approach to effectively targeting P. gingivalis colonization of the oral cavity” (p. vii).
The NP’s were synthesized using an oil-in-water technique wherein, “polyvinyl alcohol (PVA)” was included in the emulsion (p. 18, 1st full paragraph).
Accordingly, the NP’s comprised a hydrophobic polymer, PLGA, as well as a hydrophilic polymer, PVA.
BAR is taught to have the following sequence: BAR NH2-LEAAPKKVQDLLKKANITVKGAFQLFS-OH (p. 14, Table 1), as per claim 17.
The prior art teaches a composition comprising a BAR polypeptide encapsulated within a nanoparticle comprising a hydrophobic polymer, i.e., polylactic acid. Accordingly, it would have been obvious to a person having ordinary skill to make a composition comprising a BAR polypeptide encapsulated within a nanoparticle for the purpose of inhibiting pre-formed P.gingivalis/ S. gordonii biofilm, in view of Krishnan.
Since the Poly(lactic acid, PLA) and polycaprolactone (PLCL) are shown in the prior art as equivalent biodegradable polymers with poly(lactic-co-glycolic acid; PLGA) for nanoparticle synthesis. It would have been obvious to replace PLGA of the prior art embodiment with polylactic acid or polycaprolactone, as the hydrophobic polymer.
Generally, it is obvious to replace one component for another equivalent component if it is recognized in the art that two components are equivalent and is not based on the Applicant’s disclosure (see MPEP 2144.06).
Krishnan does not teach at least one hydrophilic polymer selected from claim 1.
For the sake of completion, the Examiner cites Akagi et al., teaching “Nanoparticles consisting of hydrophobic and hydrophilic segments have great potential as multifunctional carriers for pharmaceutical and biomedical applications, such as drug, protein, peptide or DNA delivery systems” (Abstract).
“Amphiphilic block or graft copolymers consisting of hydrophilic and hydrophobic segments are self-assembling materials, and are capable of forming polymeric associates in aqueous solutions” (p. 6730, right column, 3rd paragraph).
“Amphiphilic block copolymers, such as poly(ethylene glycol)-b-polylactic acid) (PEG-b-PLA) or PEG-b-PCL, are very attractive for use as drug delivery applications” (Id.). Note: polyethylene glycol is also polyethylene oxide (PEO).
Here, the prior art teaches use of polyethylene oxide a.k.a. polyethylene glycol as the hydrophilic polymer and PLA or PCL as the hydrophobic polymer.
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to combine the hydrophobic and hydrophilic polymers, i.e., PEO and PCL or PEO and PLLA (polylactic acid) since these combinations are known in the prior art as attractive for use as drug delivery applications. The artisan would have had a reasonable expectation of success with the combination insofar as the poly(lactic-co-glycolic acid of the embodiment is a mixture of hydrophobic polylactic acid and hydrophilic glycolic acid.
In regard to CafA Krishnan teaches, “In addition to specifically targeted delivery to particular niches (here in the oral cavity), surface modification may decrease the initial release of encapsulant from the NPs, aiding in prolonged release” (p. 11, 1st paragraph). “To achieve this, we envision the use of CafA adhesin. CafA or coaggregation factor A is on of the 14 cell surface proteins of Actinomyces oris that posses the LPXTG anchoring motif that is recognized by sortase . . . Surface modifications of NPs with CafA represents an approach to target NPs or fibers to streptococcal cells, a primary initial niche of P. gingivalis in the oral cavity” (Id.)
In regard to conjugation efficacy Krishnan teaches, “the level of surface associated CafA will be adjusted to increase or decrease the retention on streptococci” (p. 42, 3rd paragraph). Accordingly, "[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" (see MPEP 2144.05 IIA quoting In re Aller, 220 F.2d 454, 456 (105 USPQ 233)).
However, for the sake of completion the examiner cites Desai teaching a conjugation efficiency of CafA onto the nanoparticles “ranged from 45 to 79%” (p. 53, 1st paragraph), having a supporting Table 2 below:
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.
In regard to claim 5 Desai teaches, “The average unhydrated diameters of CaFA-modified BAR NPs and unmodified BAR NPs measured from SEM images were 89.7±26.3 and 165.8±33.4 nm, respectively” (p. 51). Here, 89.7±26.3 falls within claimed range of about 50 nm to about 100 nm.
Accordingly, it would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to provide compositions having a conjugation efficiency of CafA of at least 70% for the compositions of Krishnan in view of Desai.
Response to Arguments
Applicant argues that the Krishnan is not anticipatory or obvious over the instant claims as currently amended insofar as the claims now require CafA modification and “Krishnan does not teach or suggest how to make CafA-modified NPs having a conjugation efficiency of at least 70%” (p. 1-4).
The Examiner disagrees.
Krishnan teaches modifying NPs with CafA to aid in prolonged release of the encapsulated structure. Krishnan further teaches that the level of surface associated CafA will be adjusted to increase or decrease the retention on streptococci. Accordingly, the conjugation efficiency would have been a result effective variable, where determining result effective levels of CafA attachment, especially within the broad range instantly claimed, is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
Since the attachment of CafA modifies release from the capsule, Applicant’s data showing total quantity of BAR released from CafA-modified NPs is not surprising.
Since the prior art anticipates CafA modification applicant’s results, i.e. “higher than the amount of BAR released from unmodified NPs” (p. 39, col. 11-13) would have been inherent.
Conclusion
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER E WEBB whose telephone number is (571)270-3287 and fax number is (571) 270-4287. The examiner can normally be reached from Mon-Fri 7-3:30.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Walter E. Webb
/WALTER E WEBB/Primary Examiner, Art Unit 1612
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