DETAILED ACTION
Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/12/2026 has been entered.
Previous Rejections
Applicant’s arguments, filed January 28, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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, Second Paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 24 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 24 recites the limitation “said hyaluronic acids" in line 2. There is insufficient antecedent basis for the limitation “said hyaluronic acids” in the claim because it is unclear whether this limitation is referring back to the “crosslinked HA HMW”, the “non-crosslinked HA LMW”, or the total amount of hyaluronic acids in the composition. Appropriate correction/clarification is required.
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.
Claims 13-18, 20-24, and 26-27 are rejected under 35 U.S.C. 103 as being as being obvious over Meunier et al. (EP 3354258 A1) in view of De Rosa et al. (US 2013/0165404 A1).
Examiner’s Note: The abbreviation “HA HWM” as recited in claim 13 is defined in the specification as “high molar mass hyaluronic acid” (pg. 10, lines 1-7) and “HA LMW” is defined in the specification as “low molar mass hyaluronic acid” (pg. 9, lines 6-12).
Regarding claim 13, Meunier discloses a method for preparing an aqueous hydrogel for injection into the body [0013] with the steps of providing at least one crosslinked hyaluronic acid and at least one non-crosslinked hyaluronic acid, each independently from one another in a hydrated state and mixing them until homogenization [0044]. Hydrated state means diluted in an aqueous medium [0052] (reads on aqueous solution). The crosslinked hyaluronic acid is formed from non-crosslinked hyaluronic acid having an average molecular weight from 0.3 MDa to 10 MDa [0091] and is obtained by crosslinking non-crosslinked hyaluronic acid with a crosslinking agent [0081]. The non-crosslinked hyaluronic acid has an average molecular weight ranging from 0.3 MDa to 10 MDa [0094].
Meunier does not disclose that a ratio of low molecular weight hyaluronic acid to high molecular weight hyaluronic acid is 1:3 to 2:1.
De Rosa teaches a cooperatively hybrid complex with low molecular weight hyaluronic acid (L-HA) and high molecular weight hyaluronic acid (H-HA) for injection into the body [abstract] [0007] [0031]-[0032]. De Rosa teaches that the cooperative hybrid L/H-HA complexes can be obtained if the molecular weight of the L-HA is between 1 x 104 and 1 x 106 Da (0.01-1 MDa) and that of the H-HA is given by the formula
M
W
H
-
H
A
≥
M
W
L
-
H
A
/
0.9
[0020] (such as H-HA MW = 1.4 x 106 Da (1.4 MDa) [0035]). De Rosa teaches that the relative proportions of L-HA and H-HA, determining the stoichiometry of the hybrid, contribute to modification of their rheological properties relative to the species hybridized between them. The decrease in viscosity due to formation of the complex increases with increase of the L-HA/H-HA stoichiometric ratio used. The L-HA/H-HA stoichiometric ratio used is preferably from 0.5 to 2 [0021] [0035]-[0037]. De Rosa teaches that the systems formed with this ratio of L-HA/H-HA are stable over time, attesting to maintenance of their rheological characteristics, and have low viscosity, which allows the use of solutions of higher concentration, but are still sufficiently fluid to be injected [0021]-[0023] [0032].
Since Meunier generally teaches hyaluronic acid for injection into the body, it would have been prima facie obvious to one of ordinary skill in the art to include a ratio of low molecular weight hyaluronic acid to high molecular weight hyaluronic acid of 0.5 to 2, within the teachings of Meunier, because De Rosa teaches a L-HA/H-HA stoichiometric ratio of 0.5 to 2 for injection into the body [0021] [0035]-[0037]. An ordinarily skilled artisan would be motivated to use this ratio of L-HA to H-HA because De Rosa teaches that the systems formed with this ratio of L-HA/H-HA are stable over time, attesting to maintenance of their rheological characteristics and have low viscosity, which allows the use of solutions of higher concentration, but are still sufficiently fluid to be injected [0021]-[0023] [0032].
In regards to the molecular weights/ratios of the components, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05 A.
Examiner’s Note: “Crosslinking ratio” as recited in line 2 of claim 14 is not defined in the specification. The specification does define crosslinking rate, which is the ratio between the weight of crosslinking agent and the hyaluronic acid used for the preparation of the crosslinked hyaluronic acid (pg. 11, lines 9-13), as such, the Examiner is interpreting the crosslinking ratio to be the ratio between the crosslinking agent and the hyaluronic acid.
Claim 14 is rendered prima facie obvious because Meunier discloses the degree of crosslinking of the crosslinked hyaluronic acid ranges from 0.1 to 20% by weight, where the term "degree of crosslinking" is defined by the ratio between the crosslinking agent to the hyaluronic acid used for the crosslinking [0089]-[0090]. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 15 is rendered prima facie obvious because Meunier discloses the crosslinking agent is a bi- or multi-functional epoxy crosslinking agent, such as 1, 4- butanediol diglycidyl ether (BDDE) [0085].
Examiner’s Note: Here, for claims 16-18, the Examiner is interpreting “at least one non-crosslinked hyaluronic acid” as disclosed at [0044] of Meunier to mean that more than one non-crosslinked hyaluronic acid may be present in the composition.
Claims 16 and 17 are rendered prima facie obvious because Meunier discloses at least one non-crosslinked hyaluronic acid in the aqueous solution [0044] with average molecular weights ranging from 0.3 MDa to 10 MDa [0094]. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 18 is rendered prima facie obvious because Meunier discloses the solutions of at least one crosslinked hyaluronic acid and at least one non-crosslinked hyaluronic acid are mixed together [0044].
Claim 20 is rendered prima facie obvious because Meunier discloses the crosslinked hyaluronic acid is present in an amount of 80% to 99.9% by weight relative to the total weight of hyaluronic acid in the gel [0092] and the gel contains 1% to 4% by weight hyaluronic acid relative to the total weight of the gel [0098] (Up to ~ 40 mg/g of crosslinked hyaluronic acid). A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 21 is rendered prima facie obvious because Meunier discloses the non-crosslinked hyaluronic acid is present in an amount of 0.1% to 20% by weight relative to the total hyaluronic acid in the gel [0095] and the gel contains 1% to 4% by weight hyaluronic acid relative to the total weight of the gel [0098] (Up to 8 mg/g of non-crosslinked hyaluronic acid). A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 22 is rendered prima facie obvious because Meunier discloses the gel contains 1% to 4% by weight hyaluronic acid relative to the total weight of the gel [0098] (10 mg/g to 40 mg/g). A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 23 is rendered prima facie obvious because it would have been prima facie obvious to include a L-HA/H-HA stoichiometric ratio of 0.5 to 2, as taught by De Rosa [0021] [0035]-[0037], as previously discussed.
Claim 24 is rendered prima facie obvious because Meunier discloses the degree of crosslinking of the crosslinked hyaluronic acid ranges from 0.1 to 20% by weight [0089] and does not disclose additional modifications. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 26 is rendered prima facie obvious because Meunier discloses the compositions are sterilized by autoclaving at an effective temperature [0118] [0120]-[0125].
Claim 27 is rendered prima facie obvious because Meunier discloses the hydrogel may be packaged in a syringe and then sterilized [0118].
Response to Arguments/ Analysis of Unexpected Results
Applicant's arguments filed 01/28/2026 have been fully considered but they are not persuasive, and will be addressed insofar as they apply to the new grounds of rejection.
Applicant argues at pg. 9 that Meunier discloses that the weight ratio of non-crosslinked hyaluronic acid to crosslinked hyaluronic acid ranges from 0.001 to 0.25 (Meunier [0097]) and the Declaration filed 02/10/2026 (hereinafter the “Bourdon Declaration”) demonstrates that the particular ratio recited in the claims is critical for achieving the technical effect, namely improved resistance to degradation.
The Examiner has fully reviewed and considered the results submitted in the Bourdon Declaration.
The Bourdon Declaration shows a comparison between a composition with a non-crosslinked hyaluronic acid (MW = 0.10 MDa) and a crosslinked hyaluronic acid (MW = 4.00 MDa) at a ratio of 1:3 vs. a ratio of 1:4 (pg. 3). The results demonstrate that the ratio of 1:3 shows improved resistance to degradation compared to when the ratio is 1:4. Based on these results, the previous prior art rejection (35 U.S.C. 103 over Meunier) has been withdrawn.
However, upon further search, these results are not unexpected over the prior art (Meunier in view of De Rosa). De Rosa teaches that formation of a stable hyaluronic acid complex increases with increase of the L-HA/H-HA stoichiometric ratio used and the L-HA/H-HA stoichiometric ratio used is preferably from 0.5 to 2 [0021]-[0023] [0035]-[0037]. Therefore, one of ordinary skill in the art would reasonably expect that using a higher ratio of L-HA/H-HA would lead to the formation of a more stable hyaluronic acid complex (i.e., improved resistance to degradation) and would be motivated to combine the teachings of Meunier and De Rosa (i.e., use the ratio taught by De Rosa) for the reasons discussed above.
Furthermore, assuming purely arguendo that unexpected results have been established, (the Examiner does not believe at this time that they have), the claims would still not be “commensurate in scope” with the showing. See MPEP § 716.02(d). The Applicant has allegedly demonstrated “improved” resistance to degradation, but even if this is so then it would have only been shown with the specific ratio (1:3), and masses (0.10 MDa and 4.00 MDa) of the hyaluronic acids presented in the Bourdon Declaration. It is unclear that a comparative composition containing these specific masses and this specific ratio would be reasonably representative of compositions containing other masses and differing ratios falling within the broader scope currently claimed.
Claims 16-18 and 25 are rejected under 35 U.S.C. 103 as being as being obvious over Meunier et al. (EP 3354258 A1) in view of De Rosa et al. (US 2013/0165404 A1) and further in view of Lebreton et al. (US 2019/0350832 A1).
The 35 U.S.C. 103 rejection over Meunier in view of De Rosa was previously discussed.
Examiner’s Note: It is the Examiner’s position that “at least one non-crosslinked hyaluronic acid” at paragraph [0044] of Meunier is interpreted to mean that more than one non-crosslinked hyaluronic acid may be present in the composition, but in the interest of completeness of prosecution, purely arguendo, and for the purposes of this ground of rejection only, Meunier will be interpreted as if not teaching an additional non-crosslinked hyaluronic acid with a molar mass greater than or equal to 0.50 MDa.
In that case, Meunier does not teach an additional non-crosslinked hyaluronic acid with a molar mass greater than or equal to 0.50 MDa, as recited in claims 16-17.
Lebreton teaches a hyaluronic acid hydrogel for injection into the body [0016] [0108] with an added non-crosslinked hyaluronic acid with a molecular weight from 1.0 MDa to 4.0 MDa [0019] [0083]. Lebreton teaches that the non-crosslinked hyaluronic acid reduces the viscosity of the gel to facilitate injection into the body [0018] [claim 21].
Since Meunier generally teaches a hyaluronic acid hydrogel for injection into the body, it would have been prima facie obvious to one of ordinary skill in the art to include non-crosslinked hyaluronic acid with a molecular weight from 1.0 MDa to 4.0 MDa, within the aqueous solution of Meunier, because Lebreton teaches an added non-crosslinked hyaluronic acid with a molecular weight from 1.0 MDa to 4.0 MDa in a hyaluronic acid hydrogel for injection into the body [0019] [0083]. An ordinarily skilled artisan would have been motivated to use the non-crosslinked hyaluronic acid because Lebreton teaches that the non-crosslinked hyaluronic acid reduces the viscosity of the gel to facilitate injection into the body [0018] [claim 21]. In regards to the molar mass, a prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 18 is rendered prima facie obvious because Meunier discloses the solutions of at least one crosslinked hyaluronic acid and at least one non-crosslinked hyaluronic acid are mixed together [0044].
Regarding claim 25, Meunier discloses the gel contains 1% to 4% by weight hyaluronic acid relative to the total weight of the gel [0098] (10 mg/g to 40 mg/g). It would have been prima facie obvious to include non-crosslinked hyaluronic acid with a molecular weight from 1.0 MDa to 4.0 MDa, as taught by Lebreton, within the teachings of Meunier, as previously discussed.
The instant claim 25 recites, the gel formed has a total hyaluronic acid concentration of 20 to 30 mg/g.
Meunier taught a total hyaluronic acid concentration ranging from 10 to 40 mg/g with respect to the total mass of the aqueous gel. A prima facie case of obviousness exists because of overlap, as previously discussed.
Additionally, Meunier discloses the non-crosslinked hyaluronic acid is present in an amount of 0.1% to 20% by weight relative to the total hyaluronic acid in the gel [0095] and the crosslinked hyaluronic acid is present in an amount of 80% to 99.9% by weight relative to the total weight of hyaluronic acid in the gel [0092].
However, Meunier does not disclose the aqueous solutions comprise from 5 to 15 mg/g of crosslinked hyaluronic acid or the claimed amounts of non-crosslinked hyaluronic acid (5 to 20 mg/g and 50 to 60 mg/g), as recited in claim 25.
Lebreton discloses that the non-crosslinked hyaluronic acid (HA) solution used to form the gel has a concentration from 10 mg/g to 50 mg/g [0083] and crosslinked hyaluronic acid component has a concentration of about 15 mg/g [0024]. Lebreton teaches that a high HA concentration or highly crosslinked HA has high viscosity and lasts longer in the body and a low HA concentration or lightly crosslinked HA has a lower viscosity and has a shorter duration in the body. A higher viscosity material is more difficult to inject through a needle [0015].
Meunier is not silent as to the amount of the crosslinked/non-crosslinked hyaluronic acid in the gel. However, Lebreton teaches non-crosslinked hyaluronic acid is present in solution in an amount from 10 mg/g to 50 mg/g [0083] and crosslinked hyaluronic acid is present in an amount of about 15 mg/g [0024]. Crosslinked/non-crosslinked HA, and the concentrations thereof, are recognized to have different effects (viscosity/ease of injection, duration in the body) with changing amounts used. Thus, the general condition (concentrations of crosslinked and non-crosslinked hyaluronic acid) is known and the amount of this ingredient is recognized to be result effective. As such, result effective variables can be optimized by routine experimentation, and it would have been prima facie obvious to optimize the concentrations of crosslinked/non-crosslinked hyaluronic acid within the teachings of the prior art, as taught by Lebreton. See MPEP 2144.05.
Response to Arguments
Applicant' s arguments with respect to claim(s) 16-18 and 25 have been considered but are moot because the new ground of rejection (Meunier in view of De Rosa and Lebreton) does not rely on any reference applied in the prior rejection of record (Meunier in view of Lebreton) for any teaching or matter specifically challenged in the argument.
Claim 19 is rejected under 35 U.S.C. 103 as being as being obvious over Meunier et al. (EP 3354258 A1) in view of De Rosa et al. (US 2013/0165404 A1) and further in view of Barg et al. (US 2015/0232623 A1).
The 35 U.S.C. 103 rejection over Meunier in view of De Rosa was previously discussed.
Meunier does not disclose the formed mixture is extruded through at least one grid, as recited in claim 19.
Barg discloses a method of making a hyaluronic acid hydrogel [0001] [0076] where the formed mixture is extruded through sieves [0177]-[0178]. Barg teaches that the step of passing through sieves supports the removal of extraneous compounds and particles such as gelled particles, which negatively affect the desired homogeneity of the product. Thus, a sieving step or several sieving steps allows for the preparation of a particularly homogeneous composition [0177]-[0178].
Since Meunier generally teaches a method of making a hyaluronic acid hydrogel, it would have been prima facie obvious to one of ordinary skill in the art to include a step of passing the mixture through sieves, within the method of Meunier, because Barg teaches that after a mixture is formed it is extruded through sieves. An ordinarily skilled artisan would be motivated to use a step of passing through sieves after the mixture is formed because Barg teaches it supports the removal of extraneous compounds and particles such as gelled particles, which negatively affect the desired homogeneity of the product and a sieving step or several sieving steps allows for the preparation of a particularly homogeneous composition [0177]-[0178].
Response to Arguments
Applicant' s arguments with respect to claim 19 have been considered but are moot because the new ground of rejection (Meunier in view of De Rosa and Barg) does not rely on any reference applied in the prior rejection of record (Meunier in view of Barg) for any teaching or matter specifically challenged in the argument.
Conclusion
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/ASHLEE E WERTZ/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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