DETAILED ACTION
A non-final Office action was mailed 2 July 2025 (“Office Action”).
Applicant’s reply was received 1 October 2025 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 1, 4–11, 13, and 14 are pending. Claims 1, 9–11, and 14 are amended.
Claims 2, 3, and 12 are canceled.
Status of Rejections and Objections
The text of those sections of Title 35, U.S. Code and not included in this action can be found in the Office Action.
Unless repeated herein, any objection or rejection in the Office Action is withdrawn.
Claim Rejections - 35 U.S.C. § 103
Claims 1, 4–11, 13, and 14 are rejected under 35 U.S.C. § 103 as being unpatentable over WO2018/095576 (“Bachhav”) in view of Remington Essentials of Pharmaceutics, Chapter 28 Ophthalmic Preparations by Chowhan et al. (2012) (Ed. Linda Felton) (“Chowhan”), Remington Essentials of Pharmaceutics, Chapter 25 Sterilization Processes and Sterility Assurance by Agalloco et al. (2012) (Ed. Linda Felton) (“Agalloco”), and Garcia-Valldecabres, et al., Optometry (2004), 75, 160–168) (“Garcia”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Bachhav discloses topical formulations comprising N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide hemihydrate as the active ingredient. (Bachhav, 1:5–9) (page:lines).
Topical formulations include ophthalmic formulations. (Id., 44:24–28).
The formulation can be a gel, film, emulsion, solution, ointment, etc. (Id., 212:29–33).
Applicant acknowledges the disclosure in Bachhav may be applicable to the treatment of herpes in the eyes. (Spec., 1:19–2:3).
While several polymorphs and solvates of the compound have been identified, Bachhav states the hemihydrate is the only stable polymorph. (Bachhav, 5:4).
The formulations can be used in dissolved state or in solubilized form. (Id., 11:28–29). A preferred solvent is polyethylene glycol, including polyethylene glycol 400. (Id., 13:5–14:15).
Bachhav discloses topical formulations comprising N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide hemihydrate; a solvent selected from polyethylene glycol, PEG 400, and others; and an antioxidant; at a pH value in the range of 2.0 to 8.0. (Id., 71:6–24).
Bachhav discloses polymers like PEG having a molecular mass in a range of 300–10,000,000 g/mol. (Id., 13:15–22).
Bachhav discloses using a solvent (such as polyethylene glycol PEG 400) in an amount of 0–90% (w/w). (Id., 15:4–18).
Bachhav discloses preferred amounts of polyethylene glycol and PEG 400 for ointments of 0.1–90 % w/w and 0.1–30 % w/w, respectively. (Id., 36:21–30). Bachhav discloses preferred amounts of polyethylene glycol and PEG 400 for gels of 0.1–90 % ww and 0.1–50 % w/w, respectively. (Id., 39:3–40:8).
Bachhav discloses a dosage of N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide hemihydrate in an amount ranging from 1.0–7.5% w/w and in an amount of about 5.0% w/w. (Id., 41:2–43:18).
Chowhan explains that the majority of over-the-counter products for dry eye contain hypromellose, glycerin, polyethylene glycol, and/or povidone. (Chowhan, 558).
Chowhan explains that artificial tear solutions are useful for adjusting the viscosity of ophthalmic solutions and eyedrops. (Id., 554).
Chowhan explains, “Ophthalmic solution and suspension eyedrops may contain viscosity-imparting polymers to thicken the tear film and increase corneal contact time (i.e., reduce the rate of tear fluid drainage).” (Id., 554). Chowhan further states “The hydrophilic polymers most often used for these purposes are methylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, and polyvinyl alcohol—at concentrations that produce viscosities in the range of about 5 to 100 Centipoise.” (Id.).
Agalloco discloses methods of sterilization, including filtration. (Agalloco, 484–487). Filtration removes particles from fluids. (Id., 484). Filters for solutions can include membrane materials. (Id., 485). “Membranes with pore size ratings of 0.2 mm are typically used for sterilizing filtration.” (Id., 486). Microporous membranes are composed of various polymers, including cellulose. (Id., 485–486).
Garcia evaluated the pH of numerous (17) commercially available ophthalmic solutions, each of which containing an active ingredient and inactive ingredients. (Garcia, Tables 1 and 2). Garcia states: “According to Carney and Hill, the physiological pH is 7.45, and the ocular range is between 6.6 and 7.80 pH units. For maximum comfort, an ophthalmic solution should have the same pH as the lacrimal fluid, or the pH of the solutions should lie within the ocular comfort range.” (Garcia, 163).
Ascertaining the differences between the prior art and the claims at issue
Bachhav does not disclose an ophthalmic formulation comprising artificial tears. Chowhan is relied on for that disclosure.
Bachhav and Chowhan do not teach specific aspects of producing the ophthalmic formulation. Agalloco is relied on for that disclosure.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, ophthalmology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application includes comparisons of ophthalmic formulations comprising either the free base hemihydrate or the maleate or mesylate salt. (Spec., Example 7, 68–72). Based on the experiments conducted, the specification states “only the Pritelivir hemihydrate was suitable for the preparation of an ophthalmic formulation. (Id., 72).
The question of obviousness
Based on the above factors, it would have been obvious for a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of Bachhav, Chowhan, and Agalloco to arrive at the claimed ophthalmic formulation and method of preparing the ophthalmic formulation.
Bachhav discloses the active ingredient in various formulations, including formulations that are used in the treatment of eyes (e.g., ointment, gel). The formulations further include polyethylene glycol and PEG 400. Chowhan discloses the use of hypromellose, glycerin, polyethylene glycol, and/or povidone in formulations that are used in the treatment of eyes is very common, and those components are present in the majority of over-the-counter products for dry eye.
The process steps in claim 11 include preparing a stock solution of the active ingredient in a PEG solvent, diluting the stock solution with an artificial tears solution, adjusting the pH of the combined solution, and sterilizing the combined solution with a sterile filter. None of those steps require any knowledge or skills not possessed by one of ordinary skill in the art, as evidenced by Bachhav, Chowhan, Agalloco, and Garcia. A combination of known components for the purpose they are known for, through known means is not unexpected. Indeed, the selection of a known material based on its suitability for its intended use can support a prima facie obviousness. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945); MPEP § 2144.07. This is because: “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” (Id. at 420).
One of ordinary skill in the art would have been motivated to combine the teachings from Bachhav, Chowhan, Agalloco, and Garcia in order to optimize the pH and viscosity of a formulation for application to eye drops. One of ordinary skill in the art would have had a reasonable expectation of success in combining the disclosures because the solubility of the active ingredient in the proposed solvents was disclosed in Bachhav and the lubricants in Chowhan, Agalloco, and Garcia are commonly used for eye formulations.
Response to Arguments
Applicant’s arguments submitted with the Reply have been considered.
Applicant first argues that Bachhav teaches away from the claimed pH range because it recites a preference for a pH in the range of 4.0–5.0. (Remarks, p.8). This argument is not persuasive because a “teaching away” requires a reference to criticize, discredit, or otherwise discourage the claimed pH range. Bachhav discloses at a pH in the range of 2.0 to 8.0 and does not criticize, discredit, or otherwise discourage a pH outside of the preferred subrange of 4.0–5.0. See, e.g., In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) (“[T]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed . . .”); UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692 (Fed. Cir. 2023) (“[A] reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed.”) (citations and internal quotations omitted); MPEP § 2145(X)(D)(1).
Applicant next argues there would have been no reason to select the hemihydrate in Bachhav instead of the free base, maleate salt, or mesylate salt; or to select the glycerin, hypromellose, polyethylene glycol 400 in Chowdan. (Remarks, p.8). Characterizing those disclosures as broad, Applicant asserts there would have been no reasonable expectation of success, starting from the cited references, in obtaining the claimed formulation at a pH of 6–7 because a pH of 4.0 results in precipitation of Pritelivir hemihydrate and the maleate and mesylate salts had solubility or precipitation issues. (Id.). This argument is not persuasive. Bachhav discloses only a few analogs of Pritelivir; so, the claimed invention is not a discovery of an inconspicuous species within a broad genus. And the instant specification states Pritelivir hemihydrate is not stable in “most of the artificial tears solutions at pH 4.0” (emphasis added); i.e., the specification does not state Pritelivir hemihydrate is unstable in all artificial tears solutions at pH 4.0. In fact, Example 7 in the instant application shows Pritelivir hemihydrate was stable in an artificial tears solution at pH 4.0 at a temperature of 2–8 °C for over 4 weeks. So, Applicant’s argument is not consistent with the record. Moreover, the cited references establish a desired ocular pH range of 6.6–7.8 based on a human physiological pH of 7.45, and glycerin, hypromellose, polyethylene glycol 400 are commonly used inactive ingredients for ophthalmic solutions. In view of a prima facie case of obviousness, Applicant has not shown why obtaining the claimed formulation is an unexpected result rather than an optimization of a composition in Bachhav by modifying the pH and inactive ingredients.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 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 C.F.R. § 1.17(a)) pursuant to 37 C.F.R. § 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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to submit an Automated Interview Request: http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623