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 .
Withdrawn Objections/Rejections
The rejection of claim 4 under 35 USC § 112(b) is withdrawn in view of the claim amendments.
Claim Status
Applicants' amendments and arguments filed 03/05/2026 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Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 7 is cancelled.
Claim 11 is withdrawn.
The claims were read in view of the species elections as set forth in the Office Actions mailed 02/19/2025 and 07/10/2025. The Examiner notes that Applicant elected a component (iv) of sodium hyaluronate. Claim 4 was previously interpreted to be inclusive of the elected sodium hyaluronate as a derivative of hyaluronic acid. Amended instant claim 4 requires component (iv) is selected from hyaluronic acid, pectin, and one or more derivatives of cellulose, and thus does not read on the elected species. However, upon further search and consideration, the elected component (iv) is being rejoined with the polysaccharide hyaluronic acid.
Claims 1-6, 8-10, and 12-17 are under current examination.
Information Disclosure Statement
The information disclosure statements (IDS) submitted 02/02/2026 and 03/10/2026 have been considered by the Examiner.
Claim Interpretation
Claim 12 recites “A microemulsion obtainable by a method of manufacturing the microemulsion of claim 1, the method comprising:
(a) preparing a mixture of components (i), (iii), (iv), (v), optionally (vi), and optionally (vii), and
(b) adding component (ii) to the mixture obtained in step (a) under stirring.”
This claim is interpreted as a product-by-process claim. Per MPEP 2113, “"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).”
Here, the structure defined by the process is interpreted as a microemulsion suitable for ophthalmic administration comprising components (i)-(v) as defined in claim 1.
Rejections Maintained, Slightly Modified to Address Amended Claims
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 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.
Claims 1-6, 8-10, 12-15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Baronian (US 2010/0266710 A1, published October 12, 2010; included on IDS submitted 12/02/2022), as evidenced by Lei et al. (CN 113877000 A; of record), hereafter “Lei”, in view of Cho et al. (KR 20080024426 A, published March 18, 2008; of record), hereafter “Cho”.
Regarding instant claims 1 and 12, Baronian teaches pharmaceutical preparations comprising an active ingredient and a carrier wherein the carrier comprises an aqueous electrochemically activated salt solution (abstract, claim 1). Baronian exemplifies microemulsion formulations (see Example 1.1, table at paragraph [0024], reproduced below). Baronian teaches that preferred preparations are for ocular administration, e.g. for the treatment of glaucoma or of the dry eye syndrome (paragraph [0015]). It is therefore interpreted that the pharmaceutical formulations of Baronian are suitable for ophthalmic administration.
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The formulations of Baronian comprise the elected ethyl oleate oily component (i), water (an aqueous phase (ii)), the elected non-ionic surfactant Tween® 80 (iii) (Tween® 80 is the tradename of polyoxyethylene (80) sorbitan monooleate), the elected polysaccharide salt of sodium hyaluronate (iv), and the cross-linking agent of calcium citrate (v). While Baronian does not explicitly state that calcium citrate is a cross-linking agent, as evidenced by Lei, calcium citrate is a cross-linking agent capable of cross-linking hyaluronic acid or a salt thereof, specifically sodium hyaluronate (see abstract and claims 1, 4, and 11). Calcium citrate is also provided as component (v) in the example composition of the instant invention (see pg. 15 of the instant specification).
Regarding instant claim 2, as noted above, the formulations of Baronian comprise ethyl oleate, a fatty acid ester.
Regarding instant claim 3, as noted above, the formulations of Baronian comprise Tween 80®, a polyoxyalkylene sorbitan fatty acid ester.
Regarding instant claim 4, as noted above, the exemplified formulations of Baronian comprise sodium hyaluronate. Baronian further teaches the inclusion of hyaluronic acid (paragraph [0012]).
Regarding instant claim 5, as noted above, the formulations of Baronian comprise the elected polysaccharide salt of sodium hyaluronate (iv), and the cross-linking agent of calcium citrate (v), exemplified in the composition of Example 1 on pg. 15 of the instant specification. Per MPEP 2112.01 II., “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.” As the prior art teaches the same components (iv) and (v), the property of (v) being capable of crosslinking (iv) is necessarily present. Further, as noted above, Lei evidences that calcium citrate is a cross-linking agent capable of cross-linking hyaluronic acid or a salt thereof, specifically sodium hyaluronate (see abstract and claims 1, 4, and 11).
Regarding instant claim 6, as noted above, the formulations of Baronian comprise calcium citrate, a salt of the polycarboxylic acid citric acid.
Regarding instant claim 8, the exemplified formulations of Baronian further comprise sorbitol; from the instant specification, sorbitol is a co-surfactant in a preferred embodiment (pg. 8, paragraph 9-pg. 9; example composition on pg. 15).
Regarding instant claim 9, Baronian teaches that the preparation may be a microemulsion where the active agent may be dispersed in the presence of a lipophilic carrier and/or surfactants within the aqueous carrier (paragraph [0017]). It is therefore interpreted that the lipophilic carrier and surfactants of Baronian are dispersed in the aqueous carrier and the microemulsions are oil-in-water microemulsions.
Regarding instant claim 10, as set forth above, the formulations of Baronian comprise the elected ethyl oleate oily component (i), water (an aqueous phase (ii)), the elected non-ionic surfactant Tween® 80 (iii) (Tween 80® is the tradename of polyoxyethylene (80) sorbitan monooleate), the elected polysaccharide salt of sodium hyaluronate (iv), the cross-linking agent of calcium citrate (v), and the co-surfactant of sorbitol (vi) (see Example 1.1, table at paragraph [0024]). The amounts of components (i), (ii), (iii), (iv), and (vi) exemplified by Baronian are consistent with the amounts recited in instant claim 10.
Regarding instant claims 13-14, as noted above, the formulations of Baronian are taught to be pharmaceutical preparations (abstract). Baronian teaches that preferred preparations are for ocular administration, e.g. for the treatment of glaucoma or of the dry eye syndrome (paragraph [0015]). It is therefore interpreted that the components of the formulations are suitable for ophthalmic applications.
Regarding instant claim 15, the formulations of Baronian comprise latanoprost as an active ingredient (paragraph [0024]), a prostaglandin agent for the treatment of glaucoma (paragraph [0012]); the formulations are therefore considered to be a drug carrier.
Regarding instant claims 17, Baronian teaches that preferred preparations are for ocular administration, e.g. for the treatment of glaucoma or of the dry eye syndrome (paragraph [0015]). It is therefore interpreted that the components of the formulations are suitable for the treatment of dry eye syndrome.
Baronian does not teach calcium citrate (the cross-linking agent) is in an amount of 0.05-0.100 wt.-% (instant claims 1 and 10).
Cho teaches a hyaluronic acid derivative composition with long-term pH and viscosity stability comprising a hyaluronic acid derivative, 0.01 to 20 wt.% of a salt of an inorganic acid or an organic acid, a biocompatible substance, and water; the composition can be used for medical purposes such as eye drops (abstract, claim 1). The hyaluronic acid derivative is taught to be hyaluronic acid or sodium hyaluronate (claim 2), and the salt is taught to be calcium citrate (claim 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to adjust the amount of calcium citrate in the formulations of Baronian with the calcium citrate concentration from about 0.01 to 20% wt.% suggested by Cho, overlapping the claimed range. One of ordinary skill in the art would have been motivated to do so in order to use an amount of calcium citrate capable of providing long-term pH and viscosity stability to sodium hyaluronate compositions for medical applications such as eye drops, as suggested by Cho. There is a reasonable expectation of success as Baronian teaches that preferred preparations are for ocular administration, e.g. for the treatment of glaucoma or of the dry eye syndrome (paragraph [0015]) and example compositions comprise sodium hyaluronate and calcium citrate. Further, from MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Baronian, as evidenced by Lei, in view of Cho, as applied to claims 1-6, 8-10, 12-15, and 17 above, and further in view of Mitra et al. (US 2009/0092665 A1, published April 9, 2009; of record), hereafter “Mitra”.
The teachings of the modified Baronian are set forth above.
The combination of Baronian and Cho does not teach the inclusion of the elected species of ophthalmic drug of voclosporin.
Mitra teaches ophthalmic compositions comprising calcineurin inhibitors or mTOR inhibitors and methods for treating an ocular disease and/or condition using the compositions (abstract, claims 1, 3 and 22); the ocular disease is an inflammatory ocular surface disease, specifically dry eye syndrome (claims 23 and 25). The calcineurin inhibitor is taught to be voclosporin (claims 2, 6-7, and 26). Calcineurin inhibitors block calcineurin dephosphorylation of appropriate substances by targeting calcineurin phosphatase, a cellular enzyme that is involved in gene regulations (paragraph [0048]); voclosporin is a next-generation calcineurin inhibitor that is a more potent and less toxic semi-synthetic derivative of cyclosporine A and has been shown to extend deeper into the latch/regulatory region of calcineurin (paragraph [0058]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the formulations of Baronian to include voclosporin, as suggested by Mitra. One of ordinary skill in the art would have been motivated to do so to incorporate an active ingredient for the treatment of dry eye syndrome known as a next-generation calcineurin inhibitor that is more potent and less toxic than other molecules in its class. There is a reasonable expectation of success as Baronian teaches that preferred preparations are for ocular administration, e.g. for the treatment of glaucoma or of the dry eye syndrome (paragraph [0015]) and can include active agents for the treatment of dry eye syndrome (paragraph [0012]).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6, 8-10 and 12-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 13-14, 17, 20, and 22-25 of U.S. Patent No. 8,414,904 B2 in view of Baronian (US 2010/0266710 A1, published October 12, 2010; included on IDS submitted 12/02/2022), Cho et al. (KR 20080024426 A, published March 18, 2008; of record), hereafter “Cho”, and Mitra et al. (US 2009/0092665 A1, published April 9, 2009; of record), hereafter “Mitra”.
Claims 1-6, 8-10, and 12-17 are directed to an invention not patentably distinct from claims 1-3, 13-14, 17, 20, and 22-25 of commonly assigned U.S. Patent No. 8,414,904 B2.
Both the instant claims and those of U.S. Patent No. 8,414,904 B2 are directed to oil-in-water microemulsions comprising an oil component of ethyl oleate, an aqueous phase, at least one non-ionic surfactant including Tween® 80, and a second surfactant (interpreted as a co-surfactant), in overlapping amounts. Both sets of claims recite components suitable for ophthalmic applications. The claims of U.S. Patent No. 8,414,904 B2 recite an active agent and a composition suitable for ophthalmic use, and the emulsions of U.S. Patent No. 8,414,904 B2 are therefore considered to be a pharmaceutical composition and drug carrier. The claims of U.S. Patent No. 8,414,904 B2 recite that the emulsions can comprise further additives such as buffer agents, and viscosity-increasing compounds.
The claims of U.S. Patent No. 8,414,904 B2 do not recite a polysaccharide salt derivative of sodium hyaluronate present from 0.001-0.050 wt.% or at least one cross-linking agent of calcium citrate present from 0.05-0.100 wt.%.
Baronian teaches pharmaceutical preparations comprising an active ingredient and a carrier wherein the carrier comprises an aqueous electrochemically activated salt solution (abstract, claim 1) and pharmaceutical preparation that comprise a polysaccharide ophthalmic lubricant (claims 19 and 21). Baronian exemplifies microemulsion formulations comprising the polysaccharide salt of sodium hyaluronate present between 0.020 and 0.025 weight% (see Example 1.1, table at paragraph [0024]) and calcium citrate.
Cho teaches a hyaluronic acid derivative composition with long-term pH and viscosity stability comprising a hyaluronic acid derivative, 0.01 to 20 wt.% of a salt of an inorganic acid or an organic acid, a biocompatible substance, and water; the composition can be used for medical purposes such as eye drops (abstract, claim 1). The hyaluronic acid derivative is taught to be sodium hyaluronate (claim 2), and the salt is taught to be calcium citrate (claim 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the emulsions of U.S. Patent No. 8,414,904 B2 to include sodium hyaluronate present between 0.020 and 0.025 weight%, as suggested by Baronian and calcium citrate concentration from about 0.01 to 20% wt.% suggested by Cho, overlapping the claimed ranges. One of ordinary skill in the art would have been motivated to do so to incorporate an ingredient known to act as a lubricant in microemulsions for ophthalmic applications and to formulate a composition with long-term pH and viscosity stability for medical applications such as eye drops, as suggested by Cho. Further, from MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
The claims of U.S. Patent No. 8,414,904 B2 do not recite an ophthalmic drug of voclosporin.
Mitra teaches ophthalmic compositions comprising calcineurin inhibitors or mTOR inhibitors and methods for treating an ocular disease and/or condition using the compositions (abstract, claims 1, 3 and 22); the ocular disease can by inflammatory ocular surface disease, specifically dry eye syndrome (claims 23 and 25) or a back-of-the-eye condition such as glaucoma (paragraph [0022]). The calcineurin inhibitor is taught to be voclosporin (claims 2, 6-7, and 26). Calcineurin inhibitors block calcineurin dephosphorylation of appropriate substances by targeting calcineurin phosphatase, a cellular enzyme that is involved in gene regulations (paragraph [0048]); voclosporin is a next-generation calcineurin inhibitor that is a more potent and less toxic semi-synthetic derivative of cyclosporine A and has been shown to extend deeper into the latch/regulatory region of calcineurin (paragraph [0058]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the emulsions of U.S. Patent No. 8,414,904 B2 to include voclosporin, as suggested by Mitra. One of ordinary skill in the art would have been motivated to do so to incorporate an active ingredient for the treatment ophthalmic conditions which is known as a next-generation calcineurin inhibitor that is more potent and less toxic than other molecules in its class.
Given the subject matter of the instant claims is obvious and substantially overlaps the subject matter of U.S. Patent No. 8,414,904 B2, the instant claims are rejected on the ground of nonstatutory double patenting.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned U.S. Patent No. 8,414,904 B2, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
37 CFR 1.132 Declaration
The Examiner acknowledges receipt of the Declaration under 37 CFR 1.132 by Dr. Fabio
Carli, filed on 03/05/2026.
The Declaration provides particle size distribution results of microemulsion compositions corresponding to Example 1 of the Application with the only variable parameter of the concentration of calcium citrate. Data for calcium citrate concentrations of 0.1 wt.%, 0.2 wt.%, and 0.5 wt.% immediately after preparation and after three months of storage are presented (Fig. 1-3). The Declaration alleges that the data establish that the claimed concentration range of 0.05-0.100 wt.% of the crosslinking agent is a critical and non-arbitrary parameter for producing stable ophthalmic microemulsions suitable for ophthalmic administration; exceeding this range results in rapid particle growth, aggregation, and loss of long-term stability, and the claimed range provides unexpected and superior technical performance that would not be predictable from the teachings of the prior art (see particularly paragraphs 30-33).
The Declaration under 37 CFR 1.132 filed on 03/05/2026 is insufficient to overcome the above
rejections because:
While the Declaration provides evidence that amounts of calcium citrate higher than the claimed range result in higher particle sizes upon storage, the Declaration does not provide evidence of the criticality of the lower claimed boundary of 0.05 wt.%; rather, the Declaration suggests (emphasis added) that “restricting the calcium citrate concentration to 0.1 wt-% or below produces an unexpected technical effect” (paragraph 30). The prior art of Baronian exemplifies microemulsions consistent with those of instant claim 1 with the exception of calcium citrate present at 0.010 wt.% (below 0.1 wt.%), and the prior art of Cho teaches a range of calcium citrate of 0.01 to 20 wt%, overlapping the claimed range, in combination with sodium hyaluronate in ophthalmic compositions with excellent long-term storage properties. Per MPEP 2144.05 “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
The Declaration does not compare any tests outside the lower boundary of the claimed range such that the criticality of the range can be concluded. Per MPEP 716.02(d), “To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960)”. Seemingly to the contrary, the instant specification describes that addition of 0.03 wt% calcium citrate (outside the claimed range) leads to a large improvement of the physical stability of the microemulsion while the addition of 0.06 wt% calcium citrate (within the claimed range) did not exert any additional effect (see pg. 15-16 “Example 2-Microemulsion stability”). From the evidence of record, the Examiner cannot conclude the criticality of the claimed range, particularly as it relates to lower concentrations of calcium citrate.
The Examiner further notes that, per MPEP 716.02(e), “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979)”. Here, the closest prior art of record is Baronian, who exemplifies microemulsions consistent with those of instant claim 1 with the exception of calcium citrate present at 0.010 wt.%. Absent a direct comparison to the closest prior art, it cannot be concluded that the instant invention has achieved a result that is unexpected from the microemulsions of the prior art of Baronian.
The Examiner further notes that, per MPEP 716.02(d), evidence of unexpected results must be commensurate in scope with the claimed invention. Instant independent claim 1 is broad, drawn to a microemulsion comprising at least one oily component, an aqueous phase, at least one non-ionic surfactant, at least one polysaccharide, a salt or derivative thereof, and the at least one crosslinking agent described above. There is no further limitation on the identities or amounts of components (i)-(iv) required by instant claim 1. The Declaration exemplifies compositions consistent with Example 1 of the Application, which exemplifies a single identity and narrow concentration ranges for components (i)-(iv), and the alleged unexpected results are not commensurate in scope with the claimed invention.
Upon consideration of the facts taught by the prior art and the information submitted in this Declaration, the balance of evidence indicates that the prior art renders obvious the instantly claimed invention.
Response to Arguments
Applicant’s arguments filed 03/05/2026 have been fully considered.
Regarding the claim rejections under 35 U.S.C. 103, Applicant argues that none of Baronian, Cho, and/or Lei discloses or would have suggested the feature of at least one cross-linking agent that is Ca2+, Mg2+, a salt of Ca2+ or Mg2+, or a mixture of Ca2+ and Mg2+ or salts thereof, in an amount of 0.05- 0.100 wt.-%, wherein the microemulsion is suitable for ophthalmic administration, as recited in amended claim 1. Applicant argues that they have shown that 0.01 wt.% of calcium citrate provides inadequate stability, and the claimed 0.05-0.100 wt.% range yields significantly improved stability while maintaining acceptable viscosity. Applicant cites to the Declaration of Dr. Carli as evidence of the criticality of the claimed range, demonstrating that concentrations of cross-linking agent above 0.10 wt.% produce microemulsions that become physically unstable and are thus unsuitable for ophthalmic use.
These arguments are unpersuasive. The Declaration of Dr. Carli is addressed above; in brief summary, while the Declaration provides evidence that amounts of calcium citrate higher than the claimed range result in higher particle sizes upon storage, the Declaration does not provide evidence of the criticality of the lower claimed boundary of 0.05 wt.%. Rather, the Declaration suggests (emphasis added) that “restricting the calcium citrate concentration to 0.1 wt-% or below produces an unexpected technical effect” (paragraph 30). From the evidence of record, the Examiner cannot conclude the criticality of the claimed range, particularly as it relates to lower concentrations of calcium citrate. The Examiner further notes that the Declaration does not provide a comparison to the closest prior art of Baronian, and the results presented in the Declaration are not commensurate in scope with the instant claims (see MPEP 716.02).
Applicant further reiterates previous arguments that Baronian does not disclose calcium citrate in the amount of 0.05-0.100 wt.-% and does not recognize calcium citrate as a cross-linking agent. Applicant argues that the working examples of Cho each use sodium hyaluronate in combination with sodium citrate, and the sodium citrate concentrations are far greater than 0.100 wt.-%; there is no disclosure in the working examples of Cho of calcium salts, and Cho's disclosure would have led the skilled artisan toward sodium citrate at significantly higher concentrations, not calcium citrate at low concentrations. Applicant argues that the indicated concentration of Cho is in no way adjusted for achieving the best possible stabilization effect, and thus Cho would not suggest the claimed feature. Applicant argues that the prior art does not suggest the functional role of a cross-linking agent to stabilize a microemulsion.
These arguments are unpersuasive, and the Examiner maintains the position regarding these argument as set forth in the Office Action mailed 12/08/2025. Particularly, regarding the argument that does not recognize calcium citrate as a cross-linking agent, the Examiner respectfully maintains that the calcium citrate of Baronian has the property of being a cross-linking agent whether or not Baronian explicitly recognizes this property, as products of identical chemical composition cannot have mutually exclusive properties. Further, as noted above, Lei evidences that calcium citrate is a cross-linking agent capable of cross-linking hyaluronic acid or a salt thereof, specifically sodium hyaluronate (see abstract and claims 1, 4, and 11). The formulations of Baronian comprise the elected polysaccharide salt of sodium hyaluronate (iv), and the cross-linking agent of calcium citrate (v), exemplified in the composition of Example 1 on pg. 15 of the instant specification; per MPEP 2112.01 II., “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”.
Further, the arguments that Cho teaches away from the claimed invention by exemplifying sodium citrate in higher amounts are unpersuasive. Per MPEP 2123 II, “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)”. Here, while Cho exemplifies sodium citrate, Cho provides a clear disclosure by claiming calcium citrate in a concentration from about 0.01 to 20 wt.%, that calcium citrate in an amount overlapping the instantly claimed range is capable of providing long-term pH and viscosity stability to sodium hyaluronate compositions for medical applications such as eye drops. One of ordinary skill in the art would thus be motivated to adjust the amount of calcium citrate exemplified by Baronian within the range taught by Cho to achieve the pH and viscosity stability effect taught by Cho, particularly as the compositions of Baronian are preferably for ocular administration (paragraph [0015]). Per MPEP 2144.05 II. A, “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)”.
Applicant again cites to Example 2 and Table 1 of the present application as demonstration that calcium citrate at concentrations of 0.05 wt.-% and higher results in a marked improvement in stability over the 0.01 wt.-% level, and that the claimed range of 0.05 - 0.100 wt.-% is critical because it uniquely balances stability (which is inadequate below 0.05 wt.-%) with viscosity (which becomes unacceptable above 0.100 wt.-%).
In response, the Examiner maintains the position regarding the data of Table 1 set forth in the Office Action mailed 12/08/2025. Particularly, the Examiner cannot understand the arguments that Table 1 (reproduced below) demonstrates that calcium citrate concentrations of 0.05 wt.% demonstrate improved stability over the 0.01 wt.% level; the table does not provide any evidence regarding either of these concentrations. There is no evidence of record regarding any properties of a composition comprising calcium citrate at a concentration of 0.01 wt.% or 0.05 wt.%.
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Further, regarding Example 2, from the specification at pg. 15 (emphasis added), “The physical stability of different microemulsions was evaluated dependent on the concentration of cross-linking agent. Three microemulsions were prepared according to Example 1, whereas the concentration of calcium citrate was 0, 0.03 or 0.06 wt.-%”, and from the specification at pg. 16, “The above data show that the addition of 0.03 wt.-% of calcium citrate leads to a large improvement of the physical stability of the microemulsion with a dramatic decrease of the migration of droplets compared to the microemulsion which is free from cross-linking agent (0% calcium citrate); the addition of 0.06 wt.-% of cross-linking agent does not exert any additional effect.” From the evidence of record, one of ordinary skill in the art would not conclude that the stability of the claimed microemulsion depends critically on the claimed concentration range of calcium citrate.
Regarding the dependent claims, Applicant argues that the cited art does not suggest the particular ranges of claim 10 as Baronian’s calcium citrate concentration falls well below the claimed range, and Cho’s examples are well above the upper bound. Applicant continues to argue that Mitra does not disclose and would not have suggested the structural advantages imparted by the claimed microemulsion system, and that a reasonable expectation of success at arriving at the claimed invention has not been established as the claimed results of highly stable, homogenous microemulsions with ocular tolerability would not have been predictable.
These arguments are unpersuasive. As detailed in the above rejections, the combined teachings of the prior art teach amounts of components consistent with those recited in instant claim 10, and the evidence of record does not demonstrate the criticality of the claimed ranges. The Examiner further maintains the previous position in the Office Action mailed 12/08/2025 regarding the combination with Mitra. Particularly, Mitra is relied upon for the teaching and motivation for incorporating voclosporin in the formulation of the modified Baronian, and the test for obviousness is not that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Further, it is not necessary that the prior art suggest the combination achieve the same advantage or result discovered by Applicant (see MPEP 2144 IV).
In the present instance, Mitra provides motivation to the skilled artisan to incorporate voclosporin in the formulations of the modified Baronian in order to incorporate an active ingredient for the treatment of dry eye syndrome known as a next-generation calcineurin inhibitor that is more potent and less toxic than other molecules in its class. There is a reasonable expectation of success in arriving at the claimed microemulsion as Baronian teaches preparations for ocular administration, e.g. for the treatment of glaucoma or of the dry eye syndrome (paragraph [0015]) and can include active agents for the treatment of dry eye syndrome (paragraph [0012]).
In view of the forgoing, and as further detailed in the above rejections, the Examiner maintains that the instant claims are rendered obvious by the teachings of the modified Baronian.
Regarding the nonstatutory double patenting rejection over the claims of U.S. Patent No. 8,414,904 B2, Applicant argues that the claims are patentable over the cited claims and cited references because they do not disclose and would not have suggested one or more features recited in the claims, such as the recited cross-linking agent in an amount of 0.05 - 0.100 wt.-%.
The arguments regarding the cited art and the recited amount of cross-linking agent are addressed above. The Examiner maintains the subject matter of the instant claims is obvious and substantially overlaps the subject matter of U.S. Patent No. 8,414,904 B2, and thus nonstatutory double patenting rejections are maintained.
Conclusion
Applicant’s arguments are considered unpersuasive. Accordingly, 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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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611
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