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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/8/2026 has been entered.
Claims 9 and 12-14 have been canceled, and claims 1-8, 10-11 and 15-20 have been considered on the merits. All arguments have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 does not have a period at the end of the claim.
Claim 8 is objected to because of the following informalities: there is a missing claim number in line 1. Claim 8 was dependent on claim 1 in the previous claim set. It appears that claim number “1” was omitted inadvertently.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-8, 10-11 and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Mastelli et al. (EP2407147; IDS ref.) in view of Yamada et al. (US 2009/0274627), Tribble et al. (2000, Periodontol.) and Casale et al. (2016, Int. J. Immunopathol. Pharmacol.)
Mastelli et al. teach a method of using a composition comprising polynucleotides (PNs) and hyaluronic acid (HA) for scar-forming, re-epithelializing, bioregenerative and eutrophicating activity for a variety of connective and/or epithelial tissues (para. 1) and the connective and/or epithelial tissues include skin, bone, joints, osteotendinous and myotendinous junction, mucosa (Abstract; p.6, Claim 1).
Mastelli et al. teach that in all wound-healing processes, PN have a positive effect on damage repair, and modulate the action of many inflammatory factors (para. 19).
The composition of Mastelli et al. comprises PNs derived from natural sources of animal or plant origin (para. 15), and the use of the composition can be therapeutic and/or cosmetic regeneration and/or reparative treatment of connective and/or epithelial tissue (Abstract; para. 1).
Mastelli et al. teach that the polynucleotides are fraction of DNA that are partially depurinated (para. 15).
Mastelli et al. teach that the preferred percentage depurination of DNA lies with the range of 1-5% of purine bases removed out of the total purine bases originally present (para. 16).
Mastelli et al. teach that the PNs, preferably DNA, have a molecular weight distribution preferably within the range between 0.5 kDalton and 3000 kDalton (para. 15).
Regarding the regeneration of interdental papilla or treatment of recession of interincisal papilla (black triangle), Mastelli et al. do not teach the limitation.
Yamada et al. teach a method for regeneration of periodontal soft tissue by a composition comprising hyaluronic acid (paras. 11, 13). Yamada et al. teach that the regeneration of periodontal soft tissue includes the regeneration of the free gingiva and the gingival interdental papilla (para. 64). Yamada et al. teach that regeneration of periodontal tissue in regeneration of new connective tissue in gingiva (para. 4).
Yamada et al. teach that the repair and regeneration of soft tissue, such as the gingiva, is strongly desired from the aesthetic standpoint, and the gap formed by recession of the interdental papilla, known as the black triangle, can significantly spoil the appearance of the gums and dental alignment (para. 6), indicating that regeneration of gingiva by using HA would include the gingival recession, black triangle (para. 35, 95; Example 4).
It would have been obvious to a person skilled in the art to use the composition of Mastelli et al. for regeneration of interdental papilla or the gap formed by recession (black triangle). A person of ordinary skilled in the art would have been motivated to do so because Mastelli et al. teach that the composition comprising PNs and HA is intended for bioregeneration of epithelial and connective tissues (para. 47), and regeneration of interdental papilla is considered as bioregeneration of epithelial and connective tissues.
Regarding the treatment of periodontitis, Mastelli et al. do not teach treatment of periodontitis.
Tribble et al. teach that in gingival epithelial cells, invasion with P. gingivalis results in increased proliferation, which is associated with accelerated progression through the S-phase and up-regulating the rate of cell division may be a mechanism to maintain a reservoir of bacterially infected cells, in response to the high rate of cell turnover in the junctional epithelium (p.7, last para). Tribble et al. teach that host cell division may also allow bacterial cells to replicate without creating an overwhelming intracellular bacterial burden and in disease states, loss of cell cycle control could impact wound healing in the periodontal pocket, thus facilitating bacterial penetration of the periodontal tissues (p.7, last para). Tribble et al. teach that P. gingivalis has been detected in the periodontal connective tissue (p. 8, 1st para.).
It would have been obvious to a person skilled in the art to use the composition of Mastelli et al. in order to treat periodontitis as it is known in the art that periodontitis is a bacterial infection in periodontal tissue. According to Tribble et al., periodontal pathogens such as Porphyromonas gingivalis are well-established periodontal pathogens, and found in the subgingival sulcus of patients with chronic periodontitis (Abstract).
Based on the teaching of Tribble et al., one skilled in the art would recognize that the bacterial infection in periodontal tissue including chronic periodontitis is one of conditions treated by the composition of Mastelli et al. as the periodontal tissue is composed of epithelial tissue (gingival epithelium) and connective tissue with a reasonable expectation of success.
Furthermore, it is known in the art that HA can be used as a topical therapies for soft periodontal tissue, gingiva, periodontal ligament for chronic inflammatory disease according to Casale et al. (see Abstract). Casale et al. teach that topical HA has been recognized as an adjuvant treatment for chronic inflammatory disease including gingivitis and chronic periodontitis in addition to its use to improve healing after dental procedures (p.574; Table 1). It would have been obvious to a person skilled in the art to use the composition of Mastelli et al. comprising HA as a topical therapy for soft periodontal tissue, gingiva, periodontal ligament for chronic inflammatory disease as HA has beneficial effect in treating chronic inflammatory disease including gingivitis and chronic periodontitis taught by Casale et al.
The combined teachings of Mastelli et al. in view of Casale et al. would also meet the limitation of claim 2 directed to chronic periodontitis.
Regarding the concentration of hyaluronic acid being 1-20 mg/ml and polynucleotides being 1-20 mg/ml (claim 1) or 5-12 mg/ml (claim 10), Mastelli et al. teach that the concentration of HA is 1-20 mg/ml or 5-12 mg/ml, and the concentration of PN is 1-20 mg/ml or 5-12 mg/ml (para. 25; p.7, claim 7-8).
Regarding the wherein limitation in claim 1 directed to the combination having a synergistic effect in an in vitro study on gingival fibroblast cell viability at a concentration of 5 mg/ml of the combination of said mixture of polynucleotides and hyaluronic acid, the combined teachings of the cited references do not teach this limitation. However, the wherein clause is directed to the characteristics of the combination of polynucleotides and hyaluronic acid in an in vitro study on fibroblasts, and this characteristics is not related to the claimed method or required for the claimed method. As this limitation does not require any active step to be carried out for the claimed method, the wherein clause does not provide any patentable weight in determining patentability of the claimed method.
Regarding claims 3-5, the limitations are directed to the results obtained by the method as claimed. These limitations do not provide any active steps to be carried out and thus, they are not considered to provide any patentable weight in the claimed method. Furthermore, as the method steps taught by Mastelli et al. in view Yamada et al., Tribble et al. and Casale et al. are identical to the claimed method steps, the results from the combined teachings are expected the same as the claimed method.
Regarding claim 6, Mastelli et al. teach that the composition comprising HA and PNs is applied topically (paras. 46-47).
Regarding claim 7 directed to the treatment being carried out topical application in the periodontal pockets, Mastelli et al. in view of Casale et al. do not particularly teach the limitation. However, Mastelli et al. teach that the mixtures can be administered to oral cavity (para. 47), and one skilled in the art would recognize that periodontitis is associated with the formation of periodontal pockets (see para. 3 of the instant specification), and Casale et al. teach that HA is introduced into periodontal pockets of the patients with chronic periodontitis (p.579). Thus, it would have been obvious to a person skilled in the art to apply the composition of Mastelli et al. in the periodontal pockets of the patients with periodontitis with a reasonable expectation of success.
Regarding claim 8 directed to the local gingival infiltration in the papilla, the term “local infiltration” is not particularly defined in the instant specification, and thus, the term is interpreted as “local injection”.
Yamada et al. teach that the composition comprising HA can be for local injection into periodontal tissue including interdental papilla (para. 11).
It would have been obvious to a person skilled in the art to inject the composition of Mastelli et al. locally into the interdental papilla for regeneration of periodontal tissue with a reasonable expectation of success.
Regarding claim 11, Mastelli et al. teach that the ratio by weight of PNs and HA is between 0.2:1 and 2:1 (para. 25; p.7, claim 9).
Regarding claim 15, Mastelli et al. teach that the fraction of DNA polymer chains is preferably obtained by extraction from natural sources of animal or plant origin, such as fish or plant sperm, through a process which preferably comprises a stage of partial fragmentation of the DNA chains in order to reduce their molecular weights, and a stage of at least partial depurination of the DNA to eliminate its information-bearing capacity (para. 15).
Regarding claim 16 directed to the HA being not crosslinked, as Mastelli et al. do not disclose that the HA is crosslinked or use of any crosslinkers in preparation of HA, it is considered that the HA utilized in the method of Mastelli et al. is not crosslinked.
Regarding claim 17, Mastelli et al. teach that the molecular weight of HA is between 500 and 3000 kDalton (para. 14).
Regarding claim 18, Mastelli et al. teach that the composition of PNs and HA can be in a liquid formulation using polyols such as mannitol (para. 22). Mastelli et al. teach that the liquid form do not contain physiological saline solution (p.7, claim 14).
Regarding claim 19, Mastelli et al. teach that the osmolality of the composition in liquid form is between 10 m.o.s./l and 500 m.o.s./l (p.7, claim 15).
Regarding claim 20 directed to the dosage form, while Mastelli et al. do not particularly disclose the term, however, the liquid formations such as injectable formulations are considered as a dosage form.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments filed 4/8/2026 have been fully considered but they are not persuasive.
Applicant stated that applicants have demonstrated, within the constraints of the experimental model chosen, i.e., the in vitro culture of fibroblasts, that the combination of PN and HA shows statistically significant improvement in cell viability over the control at doses as low as 2.5 mg/ml, and the combination of the present invention provides for unexpected and surprising results which cannot be extrapolated by combining and modifying the teachings of the cited references as suggested by the Examiner.
The Examiner respectfully disagrees with the argument. While the in vitro study of the combination of PN and HA on gingival fibroblast cell viability shows unexpected results, i.e. synergistic effect, however, the concentration utilized for the claimed method is not directed to in vitro study. Furthermore, this unexpected results are not commensurate with the claimed concentration of 1-20 mg/ml of HA and 1-20 mg/ml of PN.
Unexpected results must be “commensurate in scope with the degree of protection sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Clarification is required. 2005)
As Mastelli et al. teach that there is a synergistic effect of combination of HA and PN at the concentration of 1-20 mg/ml, the same unexpected results for the claimed concentrations of HA and PN are expected in the combined teachings of Mastelli et al. in view of Yamada et al., Tribble et al. and Casale et al.
Thus, the combined teachings of the cited references render the claimed invention obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES SCHULTZ can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TAEYOON KIM/Primary Examiner, Art Unit 1631
Prosecution Insights