DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Preliminary Amendments and Remarks, filed 24 October 2024, in the matter of Application N° 18/859,689. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 17-19 and 22-24 have been canceled. No claims have been added.
Claims 7, 11, 13-16, and 20 have been amended to remove recitations of improper multiple dependency.
No new matter has been added.
Thus, claims 1-16, 20, and 21 now represent all claims currently under consideration.
Information Disclosure Statement
Three Information Disclosure Statements (IDS) filed 24 October 2024, 21 October 2025, and 2 March 2026 are acknowledged and have been considered.
Claim Rejections - 35 USC §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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 3-6, the phrases “preferably,” “more preferably,” and “particularly preferably,” render the claims indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP §2173.05(d) regarding “such as”.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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. Applicants are 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 1-16, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Mittur et al. (WO 2015/051259 A1) in view of Hashimoto (Clin. Psychopharm. Neuro.; 2014).
The limitations recited by instant claim 1 are directed to a liquid formulation comprising R-ketamine or a pharmaceutically acceptable salt thereof, an amphiphilic pharmaceutically acceptable excipient, and water, wherein the liquid formulation has a pH in the range of 2.5-5.7.
Mittur discloses in claim 7, a composition comprising:
about 2% to about 50%, preferably about 5% to about 25% or ketamine;
about 1% to about 50%, preferably about 5% to about 35% of a material that gels (i.e., tackifier);
optionally a taste-masking or flavoring agent;
optionally a permeation enhancer; and
optionally a buffering agent.
The practiced compositions are further disclosed as being provided as a liquid composition so as to enable oral, buccal, and/or sublingual delivery of an NMDA receptor agonist to a patient (see e.g., pg. 2, lines 12-14).
The reference additionally discloses that when a material that gels is employed in the practiced composition, that the composition should be free of or substantially free of water that is available to hydrate the gelling material, wherein the latter is defined as being less than 2% free or unbound water (see pg. 10, lines 14-21). The foregoing is broadly and reasonably considered as disclosing that the practiced liquid compositions may contain up to 2% by water.
The permeation enhancer is further defined as being embodied by one or more permeation enhancers (see pg. 17, lines 20-21). Therein, the permeation enhancer is defined as increasing the permeability of the NMDA receptor agonist, preferably ketamine, and such enhancers are inclusive of sodium lauryl sulfate (see pg. 17, lines 23-25). Additional permeation enhancers are taught as including EDTA (see pg. 17, line 29 and line 34 to pg. 18, line 1).
The permeation enhancer is taught as being present in the practiced composition in an amount ranging from about 0.01% to about 20% percent of the composition, preferably from about 0.1% to about 10% (see pg. 18, lines 2-4).
Such is considered to teach the compositional limitations recited by claims 1-7, 10-12, and 15.
Regarding the recited pH limitations (i.e., instant claims 1, 2, and 6), the reference discloses that the pH of the composition, and particularly a liquid, may be between the range of about 3.0 to about 9.0, and preferably about 4.0 to about 8.0 (see pg. 8, line 13 to pg. 10, line 6). Polymeric species disclosed include xanthan gum, sodium CMC, HPMC, methyl cellulose, HEC, HPC, polyvinyl alcohol, and carbomers.
The foregoing is considered to teach the limitations recited by claims 8 and 9.
The limitations of claims 13, 14, and 16 respectively recite limitations that further define the buffer, flavoring agent, and preservative.
Buffering agents are disclosed as including, for example, sodium phosphate, but may also be defined as including phosphate, carbonate, and bicarbonate systems (see pg. 18, lines 17-21).
Flavoring agents disclosed by the reference include saccharin sodium, saccharin, sucralose, menthol, aspartame, cyclamate, and acesulfame, and combinations thereof (see pg. 17, lines 9-19).
Preservatives disclosed by the reference include parabens (i.e., methyl and propyl parabens) and benzalkonium chloride (see pg. 18, lines 5-9).
Lastly, the methods recited by claims 20 and 21 are directed to a method for preventing, alleviating, or treating depression in a patient comprising administering the composition of claim 1 to the buccal membrane of the oral cavity of the patient.
Mittur discloses a method of treating depression comprising the oral, buccal, or sublingual administration of the practiced liquid compositions to a patient (see e.g., claim 8). The term depression is further defined by the reference as being inclusive of major depressive disorder (MDD).
Bipolar disorder is also disclosed as being treated with the practiced liquid compositions and as defined as being inclusive of a depressive episode (see e.g., pg. 4, lines 22-33).
The reference is noted as not expressly disclosing the “R” isomer or enantiomer of ketamine. The reference, however, does expressly disclose formulating its orally-, buccally-, or sublingually-administered compositions with ketamine. Ketamine is further defined by the reference as including isomers and enantiomers of ketamine (see pg. 6, lines 3-15). As evidenced by the teachings of Hashimoto, “[k]etamine (or RS (±)-ketamine) is a racemic mixture containing equal parts of R (-)-ketamine and S (+)-ketamine” (see Hashimoto, pg. 72, second full paragraph).
What this is considered to contribute to the teachings of Mittur is an understanding that any disclosure of ketamine, in general (as opposed to a more specific teaching such as S-ketamine), is that 50% of a disclosed amount would be expected to be in the “R” conformation or isomer. Thus, Mittur’s preferred disclosure of about 5% ketamine (see e.g., claim 7), for example, is considered as disclosing about 2.5% R-ketamine and about 2.5% S-ketamine.
Regarding Mittur’s broader disclosure of ketamine and isomers or enantiomers, the ordinarily skilled artisan would be further motivated to select the R-enantiomer over the S-enantiomer in view of Hashimoto’s discussion comparing the two. Therein, Hashimoto acknowledges that the S-enantiomer has an approximately fourfold greater affinity for NMDA receptors than does the R-stereoisomer and that it shows a three to fourfold greater anesthetic potency. However, it is also associated with more undesirable psycotomimetic side effects compared with the R-isomer. As cited, in the article, R-ketamine showed greater potency and longer-lasting antidepressant effects than did S-ketamine in a rodent model (see pg. 72, bridging paragraph).
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Art of Interest Cited
A further brief search of the prior art by the Examiner has resulted in the following document which is also considered to read on or contribute to the obviousness of the instant claims: Zhang et al. (Pharmacol Biochem Behav; 2014).
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
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