DETAILED ACTION
A requirement for restriction was mailed 4 December 2025 (“Office Action”).
Applicant’s reply to the Office Action was received 4 February 2026 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 1–7 are pending. Claims 8–34 are canceled. Claims 1–3 and 7 are amended.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2 March 2026 is acknowledged and has been considered.
Reply to Restriction Requirement
Applicant’s election without traverse of Group I (claims 1–7) in the Reply is acknowledged. Claims 8–34 (Groups II–IV) have been canceled.
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 or 103 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.
Objections to the Specification
(i) The abstract of the disclosure is objected to because it (i) is greater than 150 words in length, (ii) recites phrases that can be implied (“The present disclosure provides”), and (iii) compares the invention with prior art (“Unlike more conventional particulate drug. . .”).
Appropriate correction is required.
For guidelines on patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
(ii) The disclosure is objected to because the specification contains: (i) improper line spacing; and (ii) one or more footnotes. (Spec., p.2).
Appropriate correction is required.
Examiner recommends, for example, relocating the text from in each footnote to the paragraph where the cite is (e.g., in a parenthetical or in a new sentence).
For guidelines on patent specifications, see MPEP § 608.01 (Explaining: The written description must not include information that is not related to applicant’s invention); and MPEP § 608.01(I) (Explaining: The lines of the specification, and any amendments to the specification, must be 1 1/2 or double spaced. The text must be written in a nonscript type font, preferably with a font size of 12. The text may not be written solely in capital letters.).
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1–7 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1–3, 5, and 6 recite “about,” which is a relative term that renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention for the purpose of avoiding infringement. Importantly, the relative term “about” is used in the claims to modify the endpoints of a range. Because the claims do not indicate how much variance is allowed the endpoints are essentially undeterminable.
Regarding the range “about 10mM to about 300mM,” the specification (citations are to US 2023/0414637) describes: a niclosamide concentration of 2–3 mM to prevent replication (¶10); an increased amount of 700–800 mM of niclosamide in solution when the pH is 9.5–9.7 (¶64); a composition comprising an amount of niclosamide of 20–700 mM (¶66); etc. Thus, the specification describes amounts of niclosamide that are outside of the claimed range, and it is unclear whether amounts of niclosamide such as 3 mM and 700 mM would infringe the claimed range “about 10mM to about 300mM.”
Regarding the range “about pH 7.0 and about pH 10.0,” the specification describes: a nasal pH of ~6–7 (¶10); an increasing supernatant concentration of niclosamide as pH increases from 3.66 to above 8 (¶13); an equilibrium of niclosamide particles over a pH range of 3.65 to 9.63 (¶¶46–47); a relatively low concentration of niclosamide in aqueous solution at pH 7 (¶56); an expectation of solution equilibrium between the acid form of niclosamide and the salt form between pH 4 and 10 (¶115); etc. Accordingly, the specification describes pH values outside of the claimed range, and it is unclear whether a pH such as 5, 6, 11, or 12 would infringe the claimed range of “about pH 7.0 and about pH 10.0.”
The discussions of niclosamide concentration and pH in the specification fail to inform a person skilled in the art of any meaningful limit on the term “about.” As such, using the relative term about to modify the endpoints of the ranges renders the claims indefinite. See, e.g., Ex parte Meis, Appeal No. 2022-000556 (PTAB, Sept. 9, 2022) (Affirming examiner’s indefiniteness rejection of “about 131 °C to about 150 °C” because the claims and specification failed to inform a person skilled in the art of any meaningful limit on “about”).
Claims 4 and 7 depend from claim 1 and therefore incorporate the indefinite term without curing the deficiency.
Appropriate correction is required.
Examiner recommends deleting “about” from each range in claims 1–7.
For the purposes of examination, about will be given its plain and ordinary meaning based on the definition “reasonably close to.” (Merriam-Webster Dictionary, available at https://www.merriam-webster.com/dictionary/about (last visited 14 May 2026). The claimed “about pH 7.0” and “about pH 10.0” are interpreted to include values reasonably close to the claimed value, including at least the values adjacent to the recited value (e.g., pH 6 and pH 11).
Claim Rejections - 35 U.S.C. § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1–3 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Devarakonda et al., Int’l J. Pharmaceutics (2005), 304, 193–209 (“Devarakonda”).
Devarakonda discloses a composition comprising a buffered aqueous solution and 10–300mM of niclosamide at a pH between about pH 7.0 to about pH 10.0. (Devarakonda, pp.196–197; 202–204). In particular, Devarakonda discloses McIlvaine buffers, phosphate buffer, b- and HP-b-CD, and “standard pH buffers.” (Id., p.196). The McIlvaine buffers are pH 4 and 7. The phosphate buffer is pH 11. (Id.).
The compositions were prepared with 10mg of niclosamide in 900 mL of 35% isopropanol:water mixture, which has a molar concentration within claimed ranges. (Id., p.197).
Regarding claims 1 and 2, the term “about pH 10.0” is interpreted to include at least the value adjacent to the recited value. Accordingly, pH 11 anticipates “about pH 10.0.”
The claim term “for application to a mucus membrane of a patient” in the claim preamble is a statement of intended use and does not provide any structure to the composition. As such, any prior art composition capable of application to a mucus membrane is sufficient. The compositions in Devarakonda are capable of application to a mucus membrane in a patient.
Claim Rejections - 35 U.S.C. § 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.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claims 4–7 are rejected under 35 U.S.C. § 103 as being unpatentable over Devarakonda in view of Lauro et al. Drug Development and Industrial Pharmacy (2016), 42(7), 1127–1136 (“Lauro”), US 2009/0163408 (“Fogelman”) [IDS], and admissions in the specification (“Spec.”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
The discussion of Devarakonda in the rejection above is incorporated by reference. In addition, it explains that niclosamide is “practically insoluble in water.” (Devarakonda, p.195). “Currently, niclosamide is formulated as a suspension of the active ingredient, which may be niclosamide, its ethanolamine salt, piperazine salt or niclosamide monohydrate.” (Id.). Further, Devarakonda explains, “pH-control methods have been investigated for improving the solubility and in vitro dissolution properties of niclosamide.” (Id.).
Lauro discloses the use of carboxymethyl cellulose in oral spray compositions to enhance the dissolution of the active agent. (Lauro, entire article).
Fogelman discloses the use of ethanol as a solvent for niclosamide. (¶¶ 103–105; 249; 311; 313).
Ascertaining the differences between the prior art and the claims at issue
Regarding claim 4, Devarakonda does not disclose tris(hydroxymethyl)aminomethane or 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffers.
Regarding claim 5, Devarakonda does not disclose carboxymethyl cellulose.
Regarding claim 6, Devarakonda does not disclose the use of ethanol as a co-solvent.
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, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The specification acknowledges that known buffers other than those in claim 4 can be used for an aqueous solution comprising niclosamide:
Exemplary buffers that can be used in the compositions described herein are known in the art, and include for example, a Tris(hydroxymethyl)aminomethane buffer or a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. Additional buffers such as phosphate buffered saline (PBS), Hank's Balanced Salt Solution (HBSS), Bis-Tris Buffer, Citrate buffer, Citrate-Phosphate buffer, MOPS buffer, PIPES buffer, potassium phosphate buffer, etc., can be used depending on the situation and pH required.
(Spec., ¶67).
The specification acknowledges that excipients other than those in claim 5 can be used for an aqueous solution comprising niclosamide:
In embodiments, the compositions can further comprise additional excipients, including about 0.5% (v/v) to about 2% (v/v) carboxymethyl cellulose or other stabilizers. Additional excipients can include various antibacterial agents, thickeners, viscosity enhancers, etc.
(Spec., ¶68).
The specification does not include evidence of nonobviousness with respect to the particular buffer, excipients such as carboxymethyl cellulose, or solvents such as ethanol.
FIG. 2, shown below, shows calculations based on the Henderson-Hasselbalch equation for niclosamide as a function of pH.
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The question of obviousness
Based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed composition based on the disclosures and suggestions in the cited references because: Devarakonda discloses compositions comprising a buffered aqueous solution of niclosamide at pH 7 and 11 and the instant application suggests that other buffers are functionally equivalent to the claimed buffers depending on the situation; Lauro discloses the use of carboxymethyl cellulose in oral spray compositions; Fogelman discloses the use of ethanol as a solvent or co-solvent for niclosamide; and the instant application acknowledges that functionally equivalent excipients can be used for an aqueous solution comprising niclosamide.
One of ordinary skill in the art would have been motivated to modify Devarakonda based on the other cited references to obtain additional solubility data for compositions at a pH between 4 and 11 since Devarakonda explains niclosamide is practically insoluble. There would have been a reasonable expectation of success at arriving at the claimed invention because Devarakonda discloses an increase in solubility of niclosamide at higher pH values and modifying the pH of a solution to obtain additional solubility data is routine experimentation.
The data is the specification has been considered but does not overcome a prima facie case of obvious because it does not show a meaningful difference in the fractions for pH = 10 compared to pH = 11 (i.e., pH values within and outside of the claimed range).
Conclusion
No claims are allowed.
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.
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The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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