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 .
Status of Claims
Receipt of Remarks/Amendments filed on 03/18/2026 is acknowledged. Claims 1-9 are amended and claims 21-23 are new. Claims 9-20 remain withdrawn as being directed to a non-elected invention. Claims 1-8 and 21-23 are examined on the merits herein.
Non-Compliance of Amendments
Claims 3-4, 6, and 9 contain amendments in the body of the claim, however, their claim status does not indicate such amendments. The claim status identifier should either read (Currently Amended) or (Withdrawn – Currently Amended) for the relevant claims.
Priority
The instant application filed 09/25/2023, is a 371 filing of PCT/IB2022/053637, filed 04/19/2022, which claims foreign priority to FR2104295, filed 04/26/2021.
Withdrawn Rejections
Claims 1-8 were rejected under 35 U.S.C. 112(b). Applicant’s amendments to the claims have overcome the rejections and the rejections are withdrawn.
Claims 1 and 5-6 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen. Applicant’s amendment to claim 1 has overcome the rejection and the rejection is withdrawn.
The following grounds of rejection are new as necessitated by amendment:
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.
1. Claims 1-8 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Chausson, M., et al. (FR 3096260 A1, 11/27/2020, IDS dated 04/04/2024, US 20220220227 A1 used as English equivalent, on record), hereinafter Chausson, in view of Jing, L., et al. (US 10898613 B2, 01/26/2021, IDS dated 04/04/2024), hereinafter Jing.
Chausson discloses a crosslinked carboxyalkyl chitosan forming a matrix, compositions comprising it, a method for manufacturing it, and the different applications thereof, in particular in the field of therapy, rheumatology, ophthalmology, aesthetic medicine, plastic surgery, internal surgery, dermatology, gynecology or cosmetics (abstract). The composition of the invention may also comprise a biopolymer other than crosslinked carboxyalkyl chitosan such as hyaluronic acid or sodium hyaluronate ([0121]). The advantage of combining or crosslinking a crosslinked carboxyalkyl chitosan with another polymer is to add their biological and physicochemical properties, or even to create synergies ([0122]). Specifically, the combination of carboxyalkyl chitosan and hyaluronan combines the recognized moisturizing properties of hyaluronan with the protective properties against oxidative stress of chitosan ([0123]).
Chausson specifically teaches matrices comprising hyaluronan co-crosslinked by covalent bonds with carboxymethyl chitosan (claim 10; example 3). The matrices are provided by crosslinking a mixture of carboxymethyl chitosan of fungal origin and DA greater than 40% and hyaluronan with 1,4-butanediol diglycidyl ether (BDDE) (“co-crosslinking”). Hyaluronans (HA) with average viscosity molecular weight of 2.2 or 2.3 million (HA1 type) and 4.3 million (HA2 type) are used (Table 3a) ([0282]). The matrices form a cohesive hydrogel (claim 14; example 3a-3b). Chausson further teaches compositions comprising such a matrix which are injectable, implantable or instillable, or topically administrable pharmaceutical compositions ([0175]; claims 16-19).
Advantageously, the concentration of polymer (carboxyalkyl chitosan with or without another biopolymer, such as a hyaluronan, for example) is less than or equal to 5%, by mass relative to the total mass of the composition, and in particular of the hydrogel (m/m) ([0157]). In one embodiment, it is less than or equal to 3%, by mass ([0158]). The mass ratio (m/m) [carboxyalkyl chitosan/hyaluronan] may be from 30 to 70% or the mass ratio (m/m) [hyaluronan/carboxyalkyl chitosan] may be 30 to 70%. In one embodiment, the mass ratio (m/m) [carboxyalkyl chitosan/hyaluronan] is 1:1 (that is 50% chitosan and 50% hyaluronan) ([0159]).
As such, Chausson teaches a biocompatible product having a matrix comprising a polysaccharide (i.e., hyaluronan) and a chitosan derivative (i.e., carboxyalkyl chitosan), wherein at least part of the polysaccharide is co-crosslinked with at least a part of chitosan derivative, as defined in instant claim 1. The carboxymethyl chitosan of Chausson further reads on the chitosan derivative of instant claims 7 and 22, while the hyaluronan reads on the salt of hyaluronic acid in instant claim 8. The molecular weights of the hyaluronan of Chausson (2.2 or 4.3 million) fall within the instantly claimed range of claim 23 (i.e., 0.1-5 MDa).
The teachings of Chausson differ from that of the instant invention in that Chausson does not explicitly teach a divalent zinc cation as defined in claims 1-5 and 21, nor the explicit concentrations of each polymer as defined in claim 6.
Jing discloses improved injectable hydrogel compositions, comprising a covalently crosslinked glycosaminoglycan, such as hyaluronic acid, and a divalent cation, such as Zn2+, for use as dermal fillers and/or for slow release of the divalent cations in a subject (claim 24; col.1, lines 60-64). Such hydrogels exhibit decreased degradation during autoclaving and increased stability after autoclaving (col. 2, lines 1-13). The composition of Jing exhibits increased stability compared to an identical composition without the divalent cation (col. 7, lines 39-40). Specifically, the glycosaminoglycan of Jing is hyaluronic acid which is covalently crosslinked by the crosslinking agent 1,4-butanediol diglycidyl ether (BDDE) (claim 1; examples). The divalent cation is Zn2+ at a concentration in the range of 0.5 to 2 mM, specifically, about 1.0 mM (claims 1-4; examples). The zinc cation is provided by a Zn-salt selected from the group consisting of ZnCl2, Zn-gluconate and Zn-citrate (claim 16; col. 2, lines 62-64; example 4).
It would have been prima facie obvious to combine the teachings of Chausson and Jing before the effective filing date of the claimed invention by including the Zn2+ cation of Jing in the hydrogel matrix of Chausson, thereby yielding the instantly claimed invention. One of ordinary skill in the art would have been motivated to add the Zn2+ cation of Jing into the hyaluronan/chitosan matrix of Chausson since the addition of a divalent cation such as Zn2+ improves the stability of hyaluronic acid hydrogels as taught by Jing. One of ordinary skill in the art would have had a reasonable expectation of success in adding the Zn2+ of Jing into the matrix of Chausson since both Chausson and Jing teach injectable hydrogels comprising hyaluronic acid crosslinked by BDDE.
Regarding the concentration of the divalent zinc cation as defined in claim 1-4, Jing teaches a concentration of about 1.0 mM of Zn2+ in the hydrogel composition. While 1.0 mM differs from the instantly claimed ranges, which are in terms of weight percent, it is well within the abilities of an ordinary artisan to optimize the amount of the divalent zinc cation in the composition depending on the desired stability of the final product, using the teachings of Jing as guidance. As such, one of ordinary skill in the art would have arrived at the instantly claimed amount of divalent zinc cation, as defined in claims 2-4, through no more than routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Jing teaches that Zn2+ is added to the hydrogel via a zinc salt such as zinc chloride, zinc gluconate, or zinc citrate, which read on the zinc salts or saccharides defined in claims 5 and 21. It would have been obvious to incorporate the Zn2+ of the combined composition of Chausson and Jing via these zinc salts since they are known and effective salts for introducing a divalent zinc cation into a hydrogel. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07.
Regarding claim 6, if one combines the embodiments taught by Chausson above to provide a matrix with a total polymer concentration of 3% by mass relative to the total mass of the composition and a mass ratio [carboxyalkyl chitosan/hyaluronan] of 50:50, one of ordinary skill in the art would arrive at a concentration of 1.5% by mass each for carboxyalkyl chitosan and hyaluronan. Such an amount reads on the concentration of polysaccharide and the concentration of chitosan (derivative) as recited in claim 6. As such, one of ordinary skill in the art would have arrived at the instantly claimed invention simply by combining the teachings of Chausson. The combination of prior art elements according to known methods to yield predictable results is considered prima facie obvious. See MPEP 2143.
2. Claims 1-8 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Chausson and Jing as applied to claims 1-8 and 21-23 above, and further in view of Breton, L., et al. (FR 2919999 A1, 02/20/2009, ip.com translation used, on record), hereinafter Brenton.
The combined teachings of Chausson and Jing are discussed above.
While the combined teachings of Chausson and Jing make obvious the amount of divalent zinc cation to include in the matrix as defined in claims 1-4, neither explicitly teach a concentration of the divalent zinc cation in terms of a weight percent relative to the total weight of the matrix.
Brenton teaches a cosmetic or pharmaceutical composition comprises hyaluronic acid and/or its derivatives; and a divalent cation, in a medium, where the acid and the cation are in a form suitable for administration by injection (abstract). Brenton teaches that the coadministration of a divalent cation with hyaluronic acid prolongs the life of hyaluronic acid and thus optimizes the clinical result obtained (p. 3, para. 7). The divalent mineral cation is chosen from calcium, manganese, magnesium, manganese, copper and/or zinc (p. 8, para. 1; claim 3). The concentration of divalent cation in the composition can be adapted by those skilled in the art depending on the desired duration of action and the type of hyaluronic acid or its derivatives present. As an indication, the divalent cation concentration in the compositions is from 0.0001 to 5% by weight relative to the total weight of the composition (p. 8, para. 10). Example 4 specifically teaches solutions or gels of hyaluronic acid with molecular masses of 1-3 million Daltons prepared at a concentration of between 0.5 and 4% by volume, in which 0.5%, 0.2%, 0.05% and 0.005% of a divalent cation is introduced (p. 10-11, Ex. 4). A concentration of 0.5% and 0.2% falls within the range of claim 1 and 2. A concentration of 0.05% and 0.005% falls within the range of claims 1-4.
It would have been prima facie obvious to modify the combined teachings of Chausson and Jing with those of Brenton before the effective filing date of the claimed invention by providing the divalent zinc cation of the combined composition in an amount of 0.5%, 0.2%, 0.05% or 0.005% based on the total weight of the composition, thereby yielding the instantly claimed invention. One of ordinary skill in the art would have been motivated to add the divalent zinc cation at such concentrations in the combined matrix of Chausson and Jing since divalent cations at such an amount prolong the life of hyaluronic acid in the composition, as taught by Brenton. One of ordinary skill in the art would have had a reasonable expectation of success in making this modification since Brenton teaches such amounts as known and effective in an injectable hyaluronic acid gel for cosmetic or pharmaceutical use, which reads on the combined composition of Chausson and Jing.
Response to Arguments
Applicant's arguments filed 03/18/2026, regarding the rejections under 35 USC 103, have been fully considered but they are not persuasive:
(1) Applicant argues that there is nothing to suggest that the teachings of Jing are transferable to the matrix of Chausson (p. 7 or Remarks). Examiner respectfully disagrees given that both references teach similar injectable hydrogels comprising hyaluronic acid crosslinked by BDDE. Such hydrogels would reasonably benefit from the improved stability afforded by the Zn2+ cations taught by Jing, as discussed in the prior art rejections above. Applicant has provided no empirical evidence that the teachings of Jing are not transferable, in fact, the instant invention evidences that Zn2+ can be incorporated into carboxymethyl chitosan matrices co-cross-linked with hyaluronan, meaning the teachings of Jing are transferable.
(2) Applicant argues that Jing discourages those skilled in the art form using a concentration of divalent zinc cation in the matrix greater than 4mM (corresponding to a concentration of approximately 0.000267% by weight relative to the total weight of the matrix). As such, Applicant asserts that Jing deters the man skilled in the art from considering divalent zinc concentrations in the matrix within the instantly claimed range of 0.001 to 1%, constituting a teaching away (p. 7 of Remarks).
According to Examiners own calculations, a 4 mM concentration of Zn2+ corresponds to a concentration of approximately 0.026%, which actually falls within the instantly claimed ranges. Wherein the molecular weight of Zn2+ is 65.4 g/mol, the calculation is as follows:
4
m
M
=
0.004
M
=
0.004
m
o
l
L
x
65.4
g
m
o
l
x
1
L
1000
m
L
=
0.00026
g
/
m
L
Assuming a density of approximated 1 g/mL, weight percent can be calculated with the following formula:
W
e
i
g
h
t
P
e
r
c
e
n
t
=
M
a
s
s
o
f
s
o
l
u
t
e
T
o
t
a
l
m
a
s
s
o
f
s
o
l
u
t
i
o
n
x
100
%
W
e
i
g
h
t
P
e
r
c
e
n
t
=
0.00026
g
1
g
x
100
=
0.026
%
Since a concentration of 0.026% falls within the instantly claimed ranges, it cannot constitute a teaching away.
(3) Applicant argues that Brenton’s focus on solving the problem of inhibiting the enzyme (hyaluronidase) is far removed from the problem solved by the present application, meaning one skilled in the art would not have considered Breton. Applicant further argues that Breton only provides strong guidance for choosing calcium, magnesium, or manganese, not zinc. As such, Breton teaches away from the present application by promoting him to choose one of these divalent cations rather than zinc (p. 8 of Remarks).
In response to the first point, “[t]he reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant.” See MPEP 2144. As such, the fact that Breton addresses a different problem than the one instantly solved is permissible. One of ordinary skill would have considered Breton simply because Breton teaches that divalent cations prolong the life of hyaluronic acid in an injectable hyaluronic acid gel for cosmetic or pharmaceutical use, similar to the gels of Chausson and Jing. In response to the second point, even if Breton focuses the disclosure on divalent cations such as calcium, magnesium, and manganese, nonpreferred and alternative embodiments, such as zinc, still constitute prior art. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).” In the instant case, Breton explicitly discloses zinc divalent cations.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 SUSANNAH S ARMSTRONG whose telephone number is (571)272-0112. The examiner can normally be reached Mon-Fri 7:30-5 (Flex).
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/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616
/Mina Haghighatian/Primary Examiner, Art Unit 1616