DETAILED ACTION
Claims 185-204 were pending; claims 186-190 and 193-204 were canceled; claims 185 and 191-192 were amended; and claims 205-221 are newly added per the reply of 5/18/2026.
Claims 185, 191-192, 205-221 are pending.
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
The instant application filed 11/3/2023 is a National Stage entry of PCT/US2022/029192, International Filing Date: 5/13/2022. PCT/US2022/029192 Claims Priority from Provisional Application 63306616, filed 2/4/2022. PCT/US2022/029192 Claims Priority from Provisional Application 63188784, filed 5/14/2021.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 5/18/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statement is being considered by the Examiner.
Important Note
DUE TO THE EXTENSIVE AMENDMENTS TO THE CLAIMS, ALL THE REJECTIONS ARE NEW, AND THE ARGUMENTS BY APPLICANT ARE NOT DIRECTED TO THE REJECTIONS OF THIS ACTION.
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 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.
Claims 185, 191-192, 205-221 are rejected under 35 U.S.C. 103 as being unpatentable over Lapidus et al. “A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder,” Biol Psychiatry. 2014 December 15; 76(12): 970–976; Charney US 9592207 B2; and Canuso et al. “Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study,” Am J Psychiatry 175:7, July 2018;
Amended instant claim 185 is directed towards a method for treating a major depressive disorder (MDD) in a subject having a Clinician Administered Dissociative States Scale (CADSS) total score of 0, 1, or 2 units and a Montgomery-Asberg Depression Rating Scale (MADRS) total score from 35-60 units the method comprising intranasally administering to the subject about 90 mg of a pharmaceutical composition comprising a racemic ketamine or a pharmaceutically acceptable salt thereof.
Lapidus teaches giving 50 mg intranasal racemic ketamine to patients with a CADSS score average 0.8, a MADRS average of 30.
Lapidus doesn’t teach 90 mg dose, or the MADRS from 35-60.
Lapidus does state, “Future studies designed to optimize dosing while identifying relapse prevention strategies and biomarkers of treatment response will provide additional needed data to maximize benefit for patients and minimize side effects.”
As to the obviousness of the 90 mg dose of ketamine, Charney teaches a method of treating depression comprising intranasally administering a dose of ketamine effective to alleviate depression to a patient afflicted with depression that has not responded to at least two adequate antidepressant treatments, claim 1. Then states in claim 7, wherein the depression comprises major depressive disorder.
Charney states, the dose of dose is 0.1 mg/kg/day to about 3.0 mg/kg/day, and up to 250 mg/day, (for reference 90 mg is roughly 1.29 mg/kg for a 70 kg subject).
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 prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range).
Given that Lapidus states the dose needs to be optimized and the dose is in the range taught in the art by Charney for the same indication. A prima facia case of obviousness exists on the dose of 90 mg. Applicant can overcome this case by showing the 90 mg dose is critical, see MPEP 2144.05.
As to the obviousness of the MADR of 35-60 score, Canuso teaches a study of (S)-ketamine in a dose of 84 mg in patients with MDD and a starting MADRS score mean of 38.8. Given that the teaching of Lapidus teaches a MADRS of 30, and Canuso teaches a MADRS of 38.8, both using the same mechanism of action, and both having success, it would be obvious to use ketamine in patients with the higher MADRS as one would look to improve the lives of patients with a MADRS score from at least 30 to 38, as this was successful in the past. One would also look to go around this range as patients with depression would most likely benefit from the treatment given the art of record. The 38.8 point is within the claimed range and therefore makes a prima facie case of obviousness for the instant claims.
In regards to claims 191-192 and 219-221 to the MARDS score. Regarding the recitation, “wherein the sedation of the subject after the administration is less than the sedation exhibited by a subject administered an equivalent amount of intranasal (S)-ketamine,” or other outcomes of the score itself after dosing. This is obvious as a known property of racemic ketamine versus enantiomerically enriched (S)-ketamine. Racemic ketamine is comprised of the active and inactive form, as such the racemic administration is equivalent to given roughly half the dose of the more active (S) form. Therefore this is simply a recitation of the property of the racemic compound versus the single enantiomer. Looking to the MPEP 2111.04 discussing Claim Interpretation, we see this quote about interpreting Contingent Clauses (Wherein): the determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). In In re Giannelli, 739 F.3d 1375, 1378, 109 USPQ2d 1333, 1336 (Fed. Cir. 2014), the court found that an "adapted to" clause limited a machine claim where "the written description makes clear that 'adapted to,' as used in the [patent] application, has a narrower meaning, viz., that the claimed machine is designed or constructed to be used as a rowing machine whereby a pulling force is exerted on the handles." In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). In this method, the wherein clause is simply expressing the intended result of a process step positively recited. When a patient is given racemic ketamine, the effect will be less than giving the equivalent amount of enantiomerically enriched ketamine. Therefore, the clause is not given weight, as it simply recites the effect of the drug’s chemical property.
Claim 205 is directed to a subject having a Sheehan-Suicidality Tracking Scale (S-STS) Clinically Meaningful Change Measure (CMCM) score of at least 15 units prior to the intranasal administration. This is an odd limitation as this scale was developed around 2014 and was not used consistently during the time of the prior art, the prior art used similar scales, such as the SIBAT or just looked at the MADRS item 10. At this time this claim is considered obvious unless Applicant can show significance to this subgroup to treatment.
In regards to claims 206 and 207 as to the outcome of the CADSS score after treatment, and the MADRS score after treatment. These claims simply express the intended result of a process step positively recited, when racemic ketamine is given to a subject with MDD, in an effective dose intranasally the result of treatment will flow naturally from the treatment based on the physical properties of the drug in the human body. Therefore this limitation is not given weight toward patentability. Moreover, the art recognized an improvement in the MADRS Total Score with treatment, and as such this outcome is predicted and expected.
In regards to claims 208-215 as to a second therapy, there is no indication in the art as to having a negative effect or being contraindicated. As such using standard care in the art would be obvious in combination.
In regards to claims 216-216 as to the outcome of the AUC after treatment, and the metabolitesafter treatment. These claims simply express the intended result of a process step positively recited, when racemic ketamine is given to a subject with MDD, in an effective dose intranasally the result of treatment will flow naturally from the treatment based on the physical properties of the drug in the human body. Therefore this limitation is not given weight toward patentability.
Claim 217 is directed to a combination of claim limitations already addressed.
Claim 218 is directed to continued dosing every 3-4 days for 15 days. The continuation of dosing would be obvious as the study by Canuso gives the dose twice weekly for 4 weeks. This is therefore every 3 or 4 days, for 28 days. One would expect optimization of the effect based on outcome, as such this is obvious.
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.
US 12440457
Claims 185, 191-192, 205-221 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12440457 in view of Lapidus et al. “A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder,” Biol Psychiatry. 2014 December 15; 76(12): 970–976; and Canuso et al. “Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study,” Am J Psychiatry 175:7, July 2018.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘457 are directed to intranasally administering to the subject about 90 mg of racemic ketamine, or a pharmaceutically acceptable salt thereof, once every 3 to 4 days for 15 days, wherein ketamine is the sole therapeutic agent administered during the 15 days and once every 3 to 4 days for 15 days (Claims 2-5), and measuring and improving the MADRS score. The ‘457 patent is silent of the CADSS score, but all the studies on ketamine including the 2 cited in this rejection make sure the baseline score is low as to not confuse the data with patient that already have dissociative problems. Therefore the CADSS score of instant claims 185 would be obvious in view of the art and the claims of ‘457. Moreover, Applicant’s argument that the preamble makes the claims distinct is not true, as a high MADRS score is indicative of suicidal ideation.
17792208
Claims 185, 191-192, 205-221 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 185-200 and 205 of copending Application No. 17792208 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘208 application is directed towards a method for treating suicidality in a subject in need thereof, comprising:(a) identifying the subject as having a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from 35-60 units and a CADSS score of 0, 1, or 2; and (b) intranasally administering to the subject about 90 mg of racemic ketamine, or a pharmaceutically acceptable salt thereof, and occurs once every 3 to 4 days for 15 days, wherein ketamine is the sole therapeutic agent administered during the 15 days (Claim 206). The claims also require measuring and monitoring the MADRS score. This is only different in the preamble, and the suicidal nature is picked up in the MADRS score.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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