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 .
Priority
Acknowledgement is made that instant application 18/834,499, filed on 2024, Jun. 30 is a national stage entry of PT/EP2023/052367, filed on 2023, Jan. 31, which claims foreign priority to 22305113.7, filed on 2022, Feb. 1.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2024, Jun. 30 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 1-10 and 14-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mercier, et al. (hereafter, Mercier. EP 3110425 B1; published 2019, Nov. 13) in view of Aicher, et al. (hereafter, Aicher. US 2021/0046018 A1; published 2021, Feb. 18) as evidenced by Delmas, et al. (hereafter, Delmas. New highlights of resveratrol: a review of properties against ocular diseases. Int. J. Mol. Sci., 2021, 22(3), 1295. Doi: 10.3390/ijms22031295), further evidenced by Das, et al. (hereafter, Das. The impact of aqueous solubility and dose on the pharmacokinetic profiles of resveratrol. Pharm. Res., 2008, 25(11), 2593. Doi: 10.1007/s11095-008-9677-1), further evidenced by Snetkov, et al. (hereafter Snetkov. Hyaluronic acid: the influence of molecular weight on structural, physical, physico-chemical, and degradable properties of biopolymers. Polymers, 2020, 12(8), 1800. https://doi.org/10.3390/polym12081800), and further evidenced by Elena, et al. (hereafter, Elena. US 11,672,760 B2; published 2023, Jun. 13; filed 2021, Jul. 8).
Instant claims 1-2 are drawn to an ophthalmic composition, comprising hyaluronic or one of its salts, an oligosaccharide which is trehalose, and resveratrol, wherein the composition is aqueous.
Mercier teaches an aqueous ophthalmic solution for treating dry eye disease, comprising hyaluronic acid, or a salt thereof, and an oligosaccharide (page 3, paragraph 0001). The oligosaccharide is a diholoside that is selected from a group comprising trehalose (page 8, paragraph 0033).
The difference between the composition taught by Mercier and the instant application is that Mercier does not teach the use of resveratrol.
However, Aicher teaches ophthalmic compositions containing resveratrol and methods of use thereof to treat dry eye disease inter alia (title, abstract), wherein the composition is aqueous (page 1, paragraph 0006).
It would have been obvious for a person of ordinary skill in the art to combine the teachings of Aicher with the that of Mercier because Mercier further teaches that the pharmaceutical composition comprising may comprise one or more additional active agents, including anti-inflammatories (page 9, paragraph 0042). Prior to the filing date of the current invention, Delmas had detailed the efficacy of resveratrol on ocular disease through regulation of inflammatory processes (abstract). Therefore, a composition of hyaluronic acid, trehalose, and resveratrol would have had a reasonable expectation of success to form a superior aqueous ophthalmic composition to treat dry eye disease.
Instant claim 3 is drawn to the ophthalmic composition wherein the composition further comprises a solubilizing agent.
Aicher teaches the resveratrol composition is used with a pharmaceutically acceptable excipient, including sodium carboxymethyl cellulose (NaCMC) (page 2, paragraph 0030). NaCMC is known in the art as being a solubilizer as evidenced by Das who has previously shown carboxymethyl cellulose (CMC) to be an effective solubilizer for resveratrol. Das studied the impact of aqueous solubility and dose manipulation on the pharmacokinetics of resveratrol (purpose), wherein water-soluble formulations of resveratrol were prepared with hydroxypropyl-β-cyclodextrin (HPCD) and randomly methylated-β-cyclodextrin (RMCD), using CMC as the reference (methods). Das concluded that while both HPCD and RMCD enhanced the aqueous solubility of resveratrol, neither were as effective as CMC (results).
Instant claims 5, 17 and 27 are drawn to the ophthalmic composition wherein the composition has a pH lower than 7, the composition has a pH between 5.5 – 6.9, and the composition has a pH of 6, respectively.
Mercier teaches an ophthalmic formulation with neutral pH ranging from 6.5 to 7.5 (page 9, paragraph 0040) and Aicher further teaches embodiment 6 wherein the pH is about 6.5 to 7.5 (page 10, paragraph 0107). These pH values fall within the ranges set forth in instant claims 5 and 17, but they fail to teach an ophthalmic composition of pH = 6. However, this becomes obvious routine optimization as evidenced by Snetkov, wherein the properties of hyaluronic acid are detailed as a function of external factors, such as pH (abstract). Snetkov teaches that hyaluronic acid in solution is sensitive to pH and results in depolymerization when the pH is more than 11.0 or less than 4.0 (page 4, paragraph 6). Snetkov further teaches the mucoadhesion of hyaluronic acid increases as a result of increased acidity (page 12, paragraph 5). Therefore, one of ordinary skill in the art would have been able to optimize the pH of a hyaluronic acid solution wherein the acidity content is such that the hyaluronic acid has both improved mucoadhesion and reduced depolymerization, and additionally is not too acidic to cause the patient eye discomfort.
Instant claim 6 is drawn to the ophthalmic composition wherein the composition comprises a buffer selected from citrate, borate, and phosphate.
Aicher teaches the resveratrol composition can include one or more pharmaceutically acceptable excipients including buffering agents, including phosphates, borates, and citrates (page 4, paragraph 0043).
Instant claims 4, 16, and 26 are drawn to the ophthalmic composition wherein the composition comprises the solubilizing agent in the amounts 0.1% – 20% (w/v), 0.5 – 5% (w/v), and 0.5% or 1% (w/v), respectively.
Aicher teaches the pharmaceutically acceptable excipient (e.g., NaCMC) may be present in an amount ranging from 0.001% to about 5% w/v (page 1, paragraph 0006), which falls within the ranges and amounts set forth in instant claims 4, 16, and 26.
Instant claims 7, 18, and 28 are drawn to the ophthalmic composition wherein the composition comprises hyaluronic acid in the amounts 0.05 g – 0.5 g per 100 mL, 0.1 g – 0.2 g per 100 mL, and 0.15 g per 100 mL, respectively.
Mercier teaches the ophthalmic composition comprises hyaluronic acid or one of its salts in an amount between 0.01 – 0.5 g in 100 mL, or between 0.1 g – 0.2 g in 100 mL, or 0.15 g in 100 mL (claim 3).
Instant claims 8, 19, and 29 are drawn to the ophthalmic composition wherein the composition comprises the oligosaccharide in the amounts 0.5 g – 5 g per 100 mL, 2 g – 4 g per 100 mL, and 3 g per 100 mL, respectively.
Mercier teaches the amount of oligosaccharide constitutes between 0.5 – 5 g in 100 mL, or between 2 g – 4 g in 100 mL, or 3 g in 100 mL (claim 4).
Instant claims 9, 20, and 30 are drawn to the ophthalmic composition wherein the composition comprises resveratrol in the amounts 0.01 g – 0.1 g per 100 mL, 0.04 g – 0.06 g per 100 mL, and 0.05 g per 100 mL respectively.
Aicher teaches the amount of resveratrol ranges from 0.001% - 5% w/v (page 1, paragraph 0006), which falls within the ranges and amounts set forth in instant claims 9, 20, and 30.
Instant claim 10 is drawn to the ophthalmic composition wherein the composition is deprived of any preservative agent of the anti-microbial type.
Mercier teaches an embodiment wherein the composition is devoid of antimicrobial-type preservatives (page 11, paragraph 0047).
Instant claim 14 is drawn to a single dose or preservative free multi-dose vial containing the composition.
Aicher teaches the composition is a packaged pharmaceutical composition comprising a container holding a therapeutically effective amount of a described compound (page 9, paragraph 0089).
Instant claim 15 is drawn to the ophthalmic composition comprising a solubilizer wherein the solubilizing agent comprises macrogol hydroxystearate or polyoxyl 40 hydrogenated castor oil.
Aicher teaches the resveratrol composition is comprised of at least one pharmaceutically acceptable excipient selected from the group comprising a surfactant, wherein the surfactant is selected from a group consisting of polyethoxylated castor oil derivatives (page 4, paragraph 0043). Polyoxyl 40 hydrogenated castor oil is a polyethoxylated castor oil derivative that is known in the art in ophthalmic compositions comprising resveratrol, as evidenced by Elena who teaches formulation 06, a microemulsion for ophthalmic use comprising Kolliphor RH40 (polyoxyl 40 hydrogenated castor oil) and resveratrol (page 62, column 40). Therefore, it would have been prima facie obvious for one skilled in the art to use polyoxyl 40 hydrogenated castor oil in an ophthalmic
Instant claims 21-22 and 24 are drawn to a method of treating ocular disease by ocular administration, wherein the eye disease is dry eye disease comprising administering the above ophthalmic composition to a subject in need thereof.
Aicher teaches embodiment 13 as a method of treating dry eye disease by administering the resveratrol composition to a subject in need thereof (page 10, paragraph 0115) and further teaches embodiment 14 wherein the composition is an eye drop.
Instant claim 23 is drawn to the above method wherein the composition is administered between from at least once per day to at least ten times per day in each affected eye of a human or an animal.
Aicher teaches the use of the resveratrol composition administered to the patient ranging from one to five times per day or more (page 8, paragraph 0085), wherein “patient” is defined as any animal, including humans (page 3, paragraph 0031). Aicher further teaches the therapeutically effective amount or dose depends on the age, sex, and weight of the patient, the current medical condition of the patient, and the progression of the ocular disease (page 9, paragraph 0090). It is therefore reasonable for a skill artisan to arrive at a dosing regimen of up to ten times per day through routine optimization, should the needs of the patient not be met with less frequent administration.
Instant claim 25 is drawn to the above ophthalmic composition wherein the hyaluronic acid or its salt has a molecular weight between 100 — 800 kDa.
Mercier teaches an ophthalmic composition comprising hyaluronic acid or one of its salts, of a molecular weight between 100 and 800 kDa (claim 1; page 3, paragraph 0001).
Conclusion
Claims 1-10 and 14-30 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Paul Arcoria whose telephone number is (571)272-8719. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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