--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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 16, 2026 has been entered.
Priority
This application is a 371 of PCT/EP2020/076840 filed on 09/25/2020, and claims foreign
priority in Italian application IT 102019000017387 filed on 09/27/2019.
Claim Status
Claims 1-9, 11-13, 16, and 17 are pending. Claim 16 was amended. Claims 10, 14, and 15 were canceled. Claims 7-9 remain withdrawn. Claim 17 was newly added and reads on the
elected invention. Claims 1-6, 11-13, 16, and 17 are examined.
Withdrawn Claim Rejections - 35 USC § 112
Rejection of claim 16 over the limitation "said injectable administration" in lines 2-3 is withdrawn because the claim was amended.
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.
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 CPR 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.
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.
Claims 1-6, 11-13, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Jing (WO 2018/055002 Al Published March 29, 2018) and Picotti (US 2010/0255097 Al
Published October 7, 2010).
The claims encompass a hydrogel for topical and injectable applications, said hydrogel
containing: hyaluronic acid esterified on its free hydroxyls with lipoic acid or with lipoic acid
and forming acid, or a pharmaceutically acceptable salt thereof, and zinc gluconate.
The teachings of Jing are related to hyaluronic acid gel comprising a divalent zinc cation, and a method of preparing a sterilized injectable hydrogel composition, the method comprising the steps: a) covalently crosslinking a glycosaminoglycan using a bi- or polyfunctional
crosslinking agent to form a covalently crosslinked glycosaminoglycan, b) swelling the
covalently crosslinked glycosaminoglycan in a solution comprising a divalent zinc cation to form
a hydro gel composition, and c) sterilizing the hydro gel composition by autoclaving to form a
sterilized injectable hydrogel composition, and sterilized injectable hydrogel compositions
obtainable by such method (Abstract). The injectable hydrogel compositions are intended for use
as dermal fillers, and the compositions are preferably based on hyaluronic acid and comprise
zinc as the divalent cation (page 2 lines 16-30). The zinc cation is provided as a zinc salt selected
from Zn-gluconate (page 4 lines 18-19). It has been identified that in a hyaluronic acid gel
composition, Zn 2+ in a concentration in the range of 0.05 to 4 mM, and preferably in the range
of 0.05 to 2 mM acts to stabilize the composition, whereas higher concentrations of Zn 2+
instead cause degradation of the composition (page 4 lines 21-25). The term "hyaluronic acid"
encompasses all variants and combinations of variants of hyaluronic acid, hyaluronate or
hyaluronan, of various chain lengths and charge states, as well as with various chemical
modifications, including crosslinking. That is, the term also encompasses the various hyaluronate
salts of hyaluronic acid with various counter ions, such as sodium hyaluronate. The term also
encompasses various modifications such as esterification (page 5 lines 16-28). The molecular
weight of a single hyaluronic acid molecule is typically in the range of 0.1 - 10 MDa, but
other molecular weights are possible (page 6 lines 9-10). In certain embodiments the
concentration of the glycosaminoglycan is in the range of 1 to 100 mg/ml (page 6 lines 12-13).
The injectable hydrogel composition may further comprise a therapeutically relevant
concentration of a local anesthetic such as lidocaine (from page 8 line 30 to page 9 line 19).
Paragraph bridging pages 14-15 describes uses of the hydrogel.
Jing does not teach the claimed esterified hyaluronic acid.
The teachings of Picotti are related to polysaccharides containing residues of
glucosamine or galactosamine in the repetitive unit, characterized by the presence of esters on
the hydroxyls or amides on the amine functions, with lipoic acid or with mixtures of lipoic acid
and formic acid (Abstract). The degree of substitution (DS) of lipoic esters on the hydroxyls of
each polysaccharide monomer ranges between 0.01 and 0.5*N in the case of esters and between
0.01 and 1 for amides, where N is the number of free alcohol groups present in the repetitive
unit, while the degree of esterification of formic acid on the polymer hydroxyl groups, when it is
present, is between 0.01 and 0.2 (i.e. between 1 % and 20%). The polysaccharides derivatized
according to the invention are glycosaminoglycans such as hyaluronic acid (paragraph 0014).
The carboxyl function of the polysaccharide derivatives may be salified with alkaline metals, in
particular sodium (paragraph 0015). The molecular weight of the polysaccharide falls into the
interval between 103 and 107 Daltons, and between 104 and 106 Daltons in the case of the
hyaluronic acid derivative. The latter will preferably have a degree of esterification of lipoic acid
at the hydroxyl groups of the polymer ranging between 0.01 and 0.8, while the degree of
esterification of formic acid at the hydroxyl groups of the polymer is between 0 and 0.20, and the degree of crosslinking is between 0.001 and 0.1, as regards the ester groups between two
different hyaluronic acid chains (paragraph 0016). For example, in the case of hyaluronic acid
lipoic derivatives, by changing the synthesis conditions it is possible to obtain soluble straight chain polymers or cross-linked hydrogels containing, in addition to lipoic esters, esters between
the hydroxyl groups of one chain and the carboxyl groups of the glucuronic acid unit belonging
to a different chain. This latter bond constitutes the cross linking bridge. The hydrogels acquire
significant viscoelastic properties, which have been studied from the rheological standpoint
(paragraph 0017). The crosslinked derivatives, in hydrogel form, can be introduced into sterile
syringes and used as medical devices for intra-articular use as viscosupplementation agents and
skin fillers in cosmetic surgery. The medical devices according to the invention will contain a
hydrogel of hyaluronic acid lipoate swollen in sterile saline solution, at a polymer concentration
of between 0.5% and 3% weight/volume (paragraph 0019).
The teachings of Jing and Picotti are related to hydrogel compositions comprising ester
derivatives of hyaluronic acid where the hydrogels are intended for use as dermal fillers, and it
would have been obvious to have combined their teachings because they are in the same field of
endeavor.
Regarding claim 1, it would have been prima facie obvious to a person of ordinary skill
in the art before the effective filing date of the claimed invention to have formed a dermal filler
comprising a hydrogel comprising a crosslinked ester derivative of hyaluronic acid zinc
gluconate, with a reasonable expectation of success because Jing teaches a hydrogel
composition intended for use as a dermal filler wherein the hydrogel comprises crosslinked
hyaluronic acid and zinc gluconate and further teaches that hyaluronic acid is selected from ester
derivatives of hyaluronic acid. Jing does not teach ester derivatives of hyaluronic acid that are
suitable for use as dermal fillers and it would have been obvious to have relied on the teachings
of Picotti because Picotti is concerned with ester derivatives of hyaluronic acid that are useful as
dermal fillers. It would have been obvious to have selected hyaluronic acid having hydroxyl
groups esterified with lipoic acid or a combination of lipoic acid and formic acid, with a
reasonable expectation of success because Picotti teaches hydrogel formed from crosslinked
hyaluronic acid having hydroxyl groups esterified with lipoic acid or a combination of lipoic acid
and formic acid as suitable for use in dermal fillers. The selection of a known material based on
its suitability for its intended purpose supports obviousness and combining prior art elements
according to known methods to obtain predictable results supports obviousness. Jing' s dermal
filler hydrogel modified with Picotti comprise a hyaluronic acid esterified on its free hydroxyls
with lipoic acid or with a combination of lipoic acid and formic acid, and zinc gluconate.
Regarding claim 2, it would have been obvious to have used esterified hyaluronic acid
having a molecular weight between 104 and 106 Daltons, with a reasonable expectation of
success because Picotti teaches a molecular weight range between 104 and 106 Daltons as a
suitable range of molecular weights for the hyaluronic acid derivative. The claimed range is
obvious because it overlaps with prior art range.
Regarding claims 3 and 4, it would have been obvious to have esterified the hyaluronic
acid with lipoic acid where the number of lipoic acid residues per disaccharide unit ranges from
0.01 to 0.5, and where the number of formic acid residues per disaccharide unit of hyaluronic
acid ranges between 0.02 and 0.20 when present, with a reasonable expectation of success
because Picotti teaches that the degree of substitution (DS) of lipoic esters on the hydroxyls of
each polysaccharide monomer ranges between 0.01 and 0.5*N in the case of esters, where N is
the number of free alcohol groups present in the repetitive unit, while the degree of esterification
of formic acid on the polymer hydroxyl groups, when it is present, is between 0.01 and 0.2 (i.e.
between 1 % and 20%). The claimed ranges are obvious because they overlap with the ranges of
the prior art.
Regarding claim 5, it would have been obvious to have formed the hyaluronic acid ester
derivative as a sodium salt, with a reasonable expectation of success because Picotti teaches that
carboxyl groups of the polysaccharide derivatives may be salified with sodium.
Regarding claim 6, it would have been obvious to have formed the hyaluronic acid gel
composition of Jing as modified by Picotti by using Zn 2+ in a concentration in the range of 0.05
to 4 mM, and preferably in the range of 0.05 to 2 mM to stabilize the composition, with a
reasonable expectation of success because Picotti teaches said ranges as useful. It would have
been obvious to have formed the gel composition with hyaluronic acid derivative in the range of
1 to 100 mg/ml because Picotti teaches said range as a suitable concentration range of the
glycosaminoglycan in the composition. For calculation purpose, formulation 4c in Table 1 (page
28) is used, which contains 20 mg/mL of HA gel and 1 mM of Zn-gluconate (molecular weight
456 g/mole). One mM of Zn-gluconate is equivalent to 0.456 mg/mL. The concentration of Zn gluconate by weight of hyaluronic acid is 2.28 wt.% (0.456/20*100). This one example falls
within the claimed concentration range. A similar calculation can be done for the ranges
described in general teachings of Jing. The claimed concentration range of zinc gluconate by
weight of sodium hyaluronate lipoate or sodium hyaluronate lipoate formate is obvious because
it overlaps with the prior art range.
Regarding claims 11 and 12, it would have been obvious to have formulated the dermal
filler composition as a pharmaceutical composition or a cosmetic composition comprising
lidocaine, with a reasonable expectation of success because Jing teaches formulating the
composition with a local anesthetic such as lidocaine and the composition would have been
considered a pharmaceutical composition or a cosmetic composition. It would have been further
obvious to have filled the sterilized composition a syringe because Jing teaches that the sterilized
injectable hydrogel may be provided in the form of a pre-filled syringe (page 14 lines 1-3). This
meets the limitation of a medical device containing the hydrogel.
Regarding claim 13, Jing and Picotti teach that the hydrogel is suitable for injection as a
dermal filler. The remaining intended use of the hydrogel composition are met because the
hydrogel of Jing modified by Picotti meets all of the structural requirements of the claimed
hydrogel and could have been used for the same intended use as claimed, absent evidence to the
contrary.
Claim 16 describes an intended use of the composition according to claim 11. Jing's
composition modified with Picotti meets all of the structural requirements of the instantly
claimed composition, and Jing' s modified composition could have been administered by
injection via the claimed routs. Furthermore, Jing teaches that the composition is suitable for
injection to the dermis (page 14 lines 14-18).
Claim 17 describes properties of the hydrogel of claim 1. Jing’s hydrogel modified by Picotti meets all of the structural limitations of the instantly claimed hydrogel and it would have been reasonable to expect Jing’s hydrogel modified by Picotti to have the same properties as claimed hydrogel when placed under identical conditions. See the Federal Circuit Decision in Persion Pharmaceuticals LLC v. Alvogen Malta Operations LTD. 2018-2361, December 27, 2019.
The claimed invention is obvious over the cited references because combining prior art
elements according to known methods to obtain predictable results supports obviousness and the
selection of a known material based on its suitability for its intended purpose supports
obviousness.
Response to Arguments
Applicant submitted a declaration by Luca Stucchi to provide evidence that Picotti’s composition in Example 5, Jing’s solution of sodium hyaluronate, and presently claimed formulation have different properties.
Applicant’s declaration and arguments submitted in the remarks dated March 16, 2026, were fully considered but are not persuasive for the following reasons.
It is unknown which composition in applicant’s specification was used for testing. The specification teaches several examples of hydrogels. The applicant did not provide data sufficient to show that the results observed for the one tested hydrogel would have occurred over the entire breadth of the claims.
The rejection is based on a combination of Picotti and Jing and this combination teaches all of the structural limitations of the claimed hydrogel, and it would have been reasonable to expect Jing’s hydrogel modified by Picotti to have the same properties as claimed hydrogel when tested under the same conditions because a composition and its properties are inseparable.
Per MPEP 2112.01 PRODUCT AND APPARATUS CLAIMS - WHEN THE STRUCTURE RECITED IN THE REFERENCE IS SUBSTANTIALLY IDENTICAL TO THAT OF THE CLAIMS, CLAIMED PROPERTIES OR FUNCTIONS ARE PRESUMED TO BE INHERENT Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product.
The data and arguments are not sufficient to overcome current rejections because it has been held that rejecting a claimed property based on inherency is proper in an obviousness rejection where a combination of references was used to arrive at the claimed invention. For example, see Persion Pharms. LLC v. Alvogen Malta Operations Ltd., 2018-2361, 945 F.3d 1184 (Fed. Cir. Dec. 27, 2019), which states "To the extent Persion contends that inherency can only satisfy a claim limitation when all other limitations are taught in a single reference, that position is contrary to our prior recognition that "inherency may supply a missing claim limitation in an
obviousness analysis" where the limitation at issue is "the natural result of the combination of prior art elements." PAR, 773 F.3d at 1194-95 (emphasis added, internal quotations omitted). Here, the district court specifically found that Devane, together with Jain, the state of the prior art at the time of invention, and the Vicodin and Lortab labels, taught the combination of elements that inherently result in the claimed pharmacokinetic parameters. The district court found that a person of ordinary skill in the art would have been motivated, with reasonable expectation of success, to administer an unadjusted dose of the Devane formulation to hepatically impaired patients. There was also no dispute that the Devane formulation, which
was identical to the Zohydro ER formulation described in the patents in suit, necessarily exhibited the claimed parameters under these conditions. Pernix, 323 F. Supp. 3d at 607, 610. In this context, the district court did not err by finding that the pharmacokinetic limitations of the asserted claims were inherent and added no patentable weight to the pharmacokinetic claims." and "We too have previously explained that "an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations," because "[t]o hold otherwise would allow any formulation-no matter how obvious-to become patentable merely by testing and claiming an inherent property." Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012).
The results obtained by testing compositions that do not fall within the claimed invention (Picotti’s composition in example 5 and Jing’s hydrogel composition) are not sufficient to obviate the grounds of rejection because the skilled artisan would not have expected the inventive composition, Picotti’s composition, and Jing’s composition to have the same properties because the compositions are structurally different from each other. The data only shows that unclaimed compositions have properties that are different from a composition that falls within the claimed genus of compositions.
Applicant’s argument that the experimental evidence shows that the claimed hydrogel exhibits a combination of properties that would not have been predictable by the combination of cited references, is not persuasive because Picotti’s composition and Jing’s composition are structurally different from applicant’s composition and showing that Picotti’s composition and Jing’s composition have properties that are different from applicant’s composition is not sufficient to overcome the rejections. A person skilled the in the art would not have expected the three compositions to have the same properties because they are structurally different from each other.
Applicant’s arguments that the results are surprising and unexpected is not persuasive because they do not meet the requirements set forth in MPEP 716.02 for at least the following reasons. For instance, it is unknown which hydrogel from the specification was tested and the claimed compositions are broader in scope compared to the hydrogels disclosed in the specification. The applicant did not show that the observed properties would have occurred over the entire breadth of the claimed compositions. The applicant did not provide evidence as to why the skilled artisan would have considered the observed properties unexpected. The claimed composition is structurally different from Jing’s and Picotti’s composition, and it would have been reasonable to expect the three compositions to have different properties. The applicant did not show evidence that the results relied upon establish that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.
Conclusion
No claims are allowed.
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/ALMA PIPIC/Primary Examiner, Art Unit 1617