DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 11 May 2026 in which claim 6 was canceled, and claim 1 was amended to change the scope and breadth of the claims.
Claims 1-5 and 7-23 are pending in the current application. Claims 9-14, 21 and 23 remain withdrawn. Claims 1-5, 7, 8, 15-20 and 22 are examined on the merits herein.
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 .
Withdrawn Rejections
Applicant’s amendment, filed 11 May 2026, with respect to the rejection of claims 1-5, 7, 8, 15-20 and 22 under 35 U.S.C. § 102(a)(1)/(a)(2) as being anticipated by Liu et al., has been fully considered and is persuasive because claim 1 has been amended to recite a list of polyols. Liu et al. do not expressly disclose any of the polyols recited in amended claim 1. The rejection is hereby withdrawn.
Applicant’s amendment, filed 11 May 2026, with respect to the rejection of claims 1-6, 15, 16 and 20 under 35 U.S.C. § 102(a)(1) as being anticipated by Suner et al., has been fully considered and is persuasive because claim 1 has been amended to recite a list of polyols, which do not include sucrose (i.e. saccharose). Suner et al. do not expressly disclose any of the polyols recited in amended claim 1. The rejection is hereby withdrawn.
Response to Arguments
Applicant's arguments filed 11 May 2026 have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., HA-crosslinking agent-polyol-crosslinking agent-HA) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant contends Liu does not disclose hyaluronic acid crosslinked with the crosslinking agent and the polyol.
The above arguments have been considered, but is not found persuasive, because the term crosslinked as defined in the present Specification, appears to be the same as the term crosslinked defined in Liu et al.
According to the present Specification, “the term “crosslinked” refers to an intermolecular bond which binds individual polymer molecules or monomer chains into a more stable structure such as a gel. As such, a crosslinked polymer has at least one intermolecular bond linking at least one individual polymer to another” (p.5).
Liu et al. also disclose “As used herein, the term “crosslinked” refers to the intermolecular bonds joining the individual polymer molecules, or monomer chains, into a more stable structure like a gel. As such, a crosslinked glycosaminoglycan polymer has at least one intermolecular bond joining at least one individual polymer molecule to another one.” (see para [0052]).
Furthermore, Applicant has not provided any evidence that the polymer of Liu et al. does not form an intermolecular bond between two polymers. Thus, Applicant’s arguments that the present claimed structure is different from Liu et al. (i.e. Liu does not disclose hyaluronic acid crosslinked with the crosslinking agent and the polyol), is not found persuasive.
Like the present Application, Liu et al. is concerned with preparing hydrogels of hyaluronic acid. The formation of a hydrogel further supports the teaching by Liu et al. of preparing a crosslinked HA.
Applicant argues Andre fails to describe mannitol crosslinked with HA.
The above argument is not found persuasive. Andre was cited for teaching the use of mannitol in combination with HA-based dermal fillers. Furthermore, Andre teaches and suggests mannitol as an alternative antioxidant to the ascorbic acid derivative of Liu et al.
Applicant contends one of ordinary skill in the art would not have had a reasonable expectation of success in arriving at the claimed invention, because the purpose of Liu is to release an antioxidant through enzymes, while the purpose of the present claims is to strengthen the bonding between HA chains and maintain it.
The above arguments is not found persuasive. Liu et al. is concerned with preparing HA crosslinked with a vitamin C derivative using a crosslinking agent. The obviousness for substituting the vitamin C derivative with mannitol is discussed below (and in the previous Office Action).
In response to applicant's argument that the claimed crosslinked HA results in a robust crosslinking bridge, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant has pointed to the data comparing the Examples 1-1, 2 and 3 with various comparative examples in the Specification. Comparative Examples 2-7 are directed to commercially available dermal fillers. It is not clear how they compare in structure to the present claims. Thus, it is difficult to determine if the present claims are significantly and unexpectedly better compared to the prior art. See MPEP 716.02(b)(II), “"[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness.”.
Comparative Example 1 appears to be close to the present claims. However, it is unclear if the reported %50 Hase (Minute) for comparative example 1 is statistically and significantly better than Example 1-2, Example 2 and Example 3. See MPEP 716.02(b)(I).
Furthermore, it is not clear if these differences were based solely on the use of mannitol, or if other variables affected the hydrogels’ enzymatic susceptibility to degradation (e.g. degree of crosslinking).
For the above stated reasons, said claims are properly rejected under 35 U.S.C. 103(a). Thus, the rejection is hereby maintained.
Maintained Rejections
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.
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, 7, 8, 15-20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US Patent Application Publication No. 2021/0023265, cited in previous Office Action) in view of Andre et al. (International Journal of Cosmetic Science, 2017, vol. 39, pp. 355-360, cited in previous Office Action).
Liu et al. disclose a dermal filler composition comprising a crosslinked hyaluronic acid (HA) and an agent covalently conjugated to the crosslinked HA, wherein the agent is selected from a vitamin, an antioxidant, a growth factor, or a peptide (claim 1). The HA comprises no more than about 20% w/w of a high molecular weight HA having a molecular weight of between about 1,000,000 and about 3,000,000 Daltons (claim 6; see para [0050]). The agent is directly conjugated to the HA via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), (claim 13). The antioxidant is a polyol (claim 15). Crosslinking agents include BDDE (para [0052]). A preferable antioxidant is a vitamin C derivative, including L-ascorbic acid 2-glucoside (AA2G, i.e. 13 carbon atoms), (para [0015]):
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(fig. 1). The HA has a degree of conjugation of 5-40 mol% (para [0019]). The HA has a gel concentration varying from 17-26 mg/mL (fig. 8); also reported as mg/g (see para [0055]). The dermal filler is injectable, and has antiaging activity by functioning as a radical scavenger (see e.g. para [0022]). The dermal filler was used for treating wrinkles (example 25). The dermal filler further comprises an anesthetic agent, including lidocaine (claims 18 and 19). The composition further comprises a pharmaceutically acceptable buffer, osmolality adjusting agents and tonicity adjuster (i.e. isotonic agent) (para [0119] and [0120]). The composition can be administered via a syringe, where example 1 describes filling a syringe with the gel (para [0133]; example 1). In example 1, HA was hydrated in a syringe with alkali solution, after which AA2G and BDDE were allowed to react before being added to the hydrated HA. A HA-AA2G gel was formed.
Liu et al. do not expressly disclose maltitol (present claim 1).
Andre et al. teach mannitol has hydrating and antioxidant properties, making it ideal when combined with HA fillers (abstract). Andre et al. teach mannitol reduces the inflammation and swelling associated with injection, and prevents the degradation of the injected HA by free radicals (abstract). The addition of mannitol to HA fillers is a viable and safe option for improving short- and long-term HA aesthetic effects. Andre et al. teach vitamin C is a known natural defense mechanism used by mammalian cells as a defense mechanism to detoxify radicals (p.355-356, bridging para). Mannitol has been used as a diluent in pharmaceutical formulations, and is safe in injectable formulations (p.357). Andre et al. teach multiple HA-based dermal fillers having mannitol already exist, wherein the mannitol improved hydration effects, decreased HA depolymerization, improved skin quality, and has been used to treat wrinkles (p.358, right col to p.359). Andre et al. teach “the high degree of cross-linking in Etermis® 3 in combination with the free radical scavenging properties of mannitol acts in concert to limit early hydroxyl radical degradation of the product and contribute to its long-lasting aesthetic effect” (p.359, penultimate para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate a crosslinked HA hydrogel, wherein the HA is crosslinked with a crosslinking agent and mannitol.
Starting from Liu et al., the ordinary artisan would have looked to the teachings of Andre et al. because they are both concerned with preparing HA-based dermal fillers having antioxidant properties. The ordinary artisan would have been motivated to substitute the vitamin C derivative with mannitol in the HA-AA2G crosslinked dermal filler of Liu et al., because both vitamin C and mannitol are polyols and recognized as alternative antioxidants. Furthermore, mannitol was found to also have hydrating properties, which is particularly beneficial for their use as an aesthetic agent. Thus, they both share similar chemical functional groups and similar functional properties as antioxidants. The ordinary artisan would have had a reasonable expectation of success because mannitol is suitable for injection, and has been used in combination with HA-crosslinked dermal fillers.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is 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.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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