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 .
Status of the Application
Claims 1-21 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 06/24/2025 are acknowledged. Claim 1 has been amended and claim 21 has been added. Claims under consideration in the instant office action are claims 1-21.
Applicants' arguments, filed 06/24/2025, have been fully considered and they are not deemed to be persuasive. The rejection of claim 20 under 35 U.S.C. 103 is maintained. Applicant’s amendments, filed 06/24/2025, specifically regarding the limitation of a method of decreasing the MADRS score of a subject having MDD, necessitate new grounds of rejection since they were not previously presented and considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 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 1-17, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Murrough (WO 2016/172672) in view of Arabzadeh et al. (Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 2018, 235, pp. 236-241), Fu et al. (Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation with Intent: Double-Blind, Randomized Study (ASPIRE I), J. Clin. Psychiatry, 2020, 81(3), pp. e1-e9), and Schumann et al. (US 12,076,300, as disclosed in IDS, filed 01/24/2025).
Murrough teaches a method of treating “suicidal ideations arising from major depressive disorder (MDD) which comprises administering to a patient in need of such treatment that has been treated unsuccessfully for suicidal ideations after at least one suicide attempt and is still afflicted with suicidal ideation” wherein ketamine was administered daily (Claim 18). Murrough teaches a dosage of about 1 mg to about 250 mg (pg. 11, fourth paragraph). Murrough teaches a period of administration of at least 21 days (pg. 14, third paragraph). Regarding claims 2-5, Murrough teaches “The actual dose will vary, depending on the body weight of the patient, the severity of the patients suicidal ideations, the route of administration, the nature of medications administered concurrently, the number of doses to be administered per day, and other factors generally considered by the ordinary skilled physician in the administration of drugs.” (pg. 11, second paragraph). Murrough teaches that “Esketamine, an enantiomer of ketamine, S ( + )-ketamine, a compound two times more potent than racemic (which is a mixture of the S (+) and R (+)) is also useful in practicing the methods of the present invention.” (pg. 8, third paragraph). Murrough teaches that “The effectiveness of ketamine in reducing suicidal ideation can be measured using any of the available scales for scoring a patients suicidality-including for example the suicide item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) or the Columbia-Suicide Severity Rating Scale (C-SSRS). Prior to beginning ketamine therapy for suicidal ideation the patient is tested using one of the standard suicidality rating scales.” (pg. 9, bridging paragraph). As a consequence regarding claims 1 and 21, one of ordinary skill in the art would thus be motivated to modify the treatment regimen based on changes in the MADRS score.
Murrough does not teach a method of decreasing the MADRS score of a subject having MDD. Murrough does not teach oral administration of esketamine. Murrough does not teach administering esketamine if the patient is determined to have a MADRS score of at least 28. Murrough does not explicitly teach the recited dosages and periods of treatment. Murrough does not teach administering a second medication.
Arabzadeh et al. is drawn towards the efficacy of oral administration of ketamine in the treatment of MDD (see abstract). Arabzadeh et al. teaches “that adding oral ketamine to sertraline enhances response to therapy. The most important finding was an early improvement of symptoms in patients that received ketamine compared to those that received placebo. The antidepressant effects of oral ketamine were still present after 6 weeks of treatment. Overall, these results are broadly compatible with previous reports on the effectiveness of oral ketamine treatment in depression” (pg. 238, right column, third paragraph).
Fu et al. is drawn towards the use of an esketamine nasal spray for the treatment of MDD symptoms (see abstract). Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). As a consequence it would follow that one of ordinary skill in the art would not administer esketamine to a patient with MDD wherein their MADRS score is below 28 since they were excluded from eligibility as taught by Fu et al. above. Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph).
Schumann et al. is drawn towards “methods for safe and efficacious administration of esketamine (see abstract). Regarding the limitations “decreasing the Montgomery-Asberg Depression Rating Scale (MADRS) score of a subject having major depressive disorder (MDD)” and “determining or having determined said subject's baseline Montgomery-Asberg Depression Rating Scale (MADRS) score” as amended on 06/24/2025, Schumann et al. teaches “the term "treating major depressive disorder" can refer to a reduction of the symptoms of Major Depressive Disorder, as measured by reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score. In some aspects, the term "treating major depressive disorder" refers to a change from baseline, as measured the MADRS score. In some aspects, the term "treating major depressive disorder" refers to a remission, as measured by reduction in the MADRS score. In some aspects, the term "treating major depressive disorder" refers to a 50% or greater improvement, as measured the MADRS score.” (col. 4, lines 10-20). Schumann et al. teaches esketamine preferably formulated for oral administration in an amount of 60 mg (col. 7, lines 51-54). Schumann et al. teaches a treatment period of at least 28 days (col. 7, lines 4-12, 22-27). Schumann teaches esketamine in the form of a hydrochloride salt (col. 5, lines 45-48).
It would have been obvious to one of ordinary skill in the art to decrease the MADRS score of a subject having MDD, as suggested by Schumann et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Schumann et al. teaches that treating MDD can refer to reducing the MADRS score of the patient as taught by Schumann et al. (col. 4, lines 10-20), with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to orally administer esketamine, as suggested by Arabzadeh et al. and Schumann, and produce the instant invention.
It would have been obvious to one of ordinary skill in the art to administer esketamine if the patient is determined to have a MADRS score of at least 28, as suggested by Fu et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fu et al. teaches a MADRS greater than 28 as an eligibility criterion, and that MDD patients with a higher MADRS score favor esketamine, with a reasonable expectation of success absent evidence of criticality of the particular steps.
One of ordinary skill in the art would have been motivated to combine esketamine and sertraline to treat major depressive disorder since it is prima facie obvious to combine components known for the same purpose for their combined additive effects, with a reasonable expectation of success absent evidence of criticality of the particular formulation. Additionally, “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
When the composition recitations are met, the desired properties are met, as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope (i.e. claim 1). Additionally, when the composition is delivered in the same manner as claimed, the effects of the composition would be the same such as the therapeutic profile, as they are a direct result of the components of the composition and the mode of administration which are met by the art, whereby the resulting properties and effects would intrinsically be met. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
Claim 18-20 is rejected under 35 U.S.C. 103 as being unpatentable over Murrough (WO 2016/172672) in view of Arabzadeh et al. (Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 2018, 235, pp. 236-241) and Fu et al. (Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation with Intent: Double-Blind, Randomized Study (ASPIRE I), J. Clin. Psychiatry, 2020, 81(3), pp. e1-e9).
Murrough teaches a method of treating “suicidal ideations arising from major depressive disorder (MDD) which comprises administering to a patient in need of such treatment that has been treated unsuccessfully for suicidal ideations after at least one suicide attempt and is still afflicted with suicidal ideation” wherein ketamine was administered daily (Claim 18). Murrough teaches a dosage of about 1 mg to about 250 mg (pg. 11, fourth paragraph). Murrough teaches a period of administration of at least 21 days (pg. 14, third paragraph). Regarding claims 2-5, Murrough teaches “The actual dose will vary, depending on the body weight of the patient, the severity of the patients suicidal ideations, the route of administration, the nature of medications administered concurrently, the number of doses to be administered per day, and other factors generally considered by the ordinary skilled physician in the administration of drugs.” (pg. 11, second paragraph). Murrough teaches that “Esketamine, an enantiomer of ketamine, S ( + )-ketamine, a compound two times more potent than racemic (which is a mixture of the S (+) and R (+)) is also useful in practicing the methods of the present invention.” (pg. 8, third paragraph). Murrough teaches that “The effectiveness of ketamine in reducing suicidal ideation can be measured using any of the available scales for scoring a patients suicidality-including for example the suicide item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) or the Columbia-Suicide Severity Rating Scale (C-SSRS). Prior to beginning ketamine therapy for suicidal ideation the patient is tested using one of the standard suicidality rating scales.” (pg. 9, bridging paragraph).
Murrough does not teach oral administration of esketamine. Murrough does not teach administering esketamine if the patient is determined to have a MADRS score of at least 28. Murrough does not explicitly teach the recited dosages and periods of treatment. Murrough does not teach administering a second medication.
Arabzadeh et al. is drawn towards the efficacy of oral administration of ketamine in the treatment of MDD (see abstract). Arabzadeh et al. teaches “that adding oral ketamine to sertraline enhances response to therapy. The most important finding was an early improvement of symptoms in patients that received ketamine compared to those that received placebo. The antidepressant effects of oral ketamine were still present after 6 weeks of treatment. Overall, these results are broadly compatible with previous reports on the effectiveness of oral ketamine treatment in depression” (pg. 238, right column, third paragraph).
Fu et al. is drawn towards the use of an esketamine nasal spray for the treatment of MDD symptoms (see abstract). Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). As a consequence it would follow that one of ordinary skill in the art would not administer esketamine to a patient with MDD wherein their MADRS score is below 28 since they were excluded from eligibility as taught by Fu et al. above. Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph).
It would have been obvious to one of ordinary skill in the art to orally administer esketamine, as suggested by Arabzadeh et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Arabzadeh et al. teaches that oral administration of ketamine with sertraline, which is an SSRI, enhances response to therapy for MDD, with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to administer esketamine if the patient is determined to have a MADRS score of at least 28, as suggested by Fu et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fu et al. teaches a MADRS greater than 28 as an eligibility criterion, and that MDD patients with a higher MADRS score favor esketamine, with a reasonable expectation of success absent evidence of criticality of the particular steps.
Even though the range for dosages and treatment periods as taught by Murrough and Arabzadeh et al. is not the same as the claimed dosages and treatment periods, Murrough and Arabzadeh et al. do teach an overlapping range of dosages and periods of administration, and it has been held that 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). See MPEP § 2144.05(I). Furthermore, the determination of dosages and treatment frequency is well within the purview of those skilled in the art through routine experimentation, and it has been held that “it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05(II). It would have been obvious to one of ordinary skill in the art to optimize the dosages and periods of treatment in order to increase the efficacy of the composition.
The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration.
Furthermore, no unobviousness is seen in the ratio claimed because once the usefulness of a compound is known to treat a condition, it is within the skill of the artisan to determine the optimum ratio.
One of ordinary skill in the art would have been motivated to combine esketamine and sertraline to treat major depressive disorder since it is prima facie obvious to combine components known for the same purpose for their combined additive effects, with a reasonable expectation of success absent evidence of criticality of the particular formulation. Additionally, “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
When the composition recitations are met, the desired properties are met, as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope (i.e. claim 1). Additionally, when the composition is delivered in the same manner as claimed, the effects of the composition would be the same such as the therapeutic profile, as they are a direct result of the components of the composition and the mode of administration which are met by the art, whereby the resulting properties and effects would intrinsically be met. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
Response to Arguments
Applicant argues that “The scientific literature did not contemplate or suggest that an MDD patient's esketamine treatment outcome should be correlated to their baseline MADRS score, nor has the Office alleged that such a correlation should have been expected. Applicant requests reconsideration and withdrawal of the obviousness rejections in view of Nikolin's silence as to the possibility that any claimed method might be successful.” The Examiner respectfully disagrees since Nikolin et al. is a review article and does not provide an analysis of the patentability of the claimed invention or for any given method of treating MDD by administering esketamine. For the purposes of examination, the art is considered for anticipation and/or obviousness as it applies to all patent statutes and laws. In reference, to Applicant’s assertion of the paradigm shift in how MDD patients can be treated, notably Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph). Fu et al. teaches a patient population wherein the mean MADRS score is 41.3 reads on the limitation of a MADRS score of at least 28 and supports the fact that a higher score equates to disease severity (see Table 1). One of ordinary skill in the art would have thus been motivated to select MDD patients based on their MADRS score, and the determination of the threshold levels of a patient’s MADRS score can be determined through routine experimentation and optimization.
Applicant also argues that “Applicant submitted detailed arguments and expert testimony to
traverse the obviousness rejections and in each case, those arguments and testimony were found
persuasive.” The Examiner respectfully disagree since although Applicant has provided the full file histories of prior prosecutions of various applications and patents, the findings of the prosecution history of other patent applications is not binding on the examination of the instant application. Additionally, the finding of non-obviousness of the invention claimed in U.S. Application No. 18/193,083 did not address the prior art of record of the instant application.
Applicant also argues that “Nothing in Fu, or the cited documents, suggests that the magnitude of the baseline MADRS score should be used to determine an MDD patient's course of treatment. Moreover, it is surprising that such significant improvements in MADRS score would be observed in those subjects having a baseline MADRS ≥ 28.” The Examiner respectfully disagrees since such results would have been expected given that Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph), and that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph). One of ordinary skill in the art would thus expect that esketamine administration can significantly improve depression severity based on a MADRS score greater than 28, with a reasonable expectation of success absent evidence of criticality of the particular steps. Additionally, one of ordinary skill in the art would have been motivated to not administer esketamine to a patient having a MADRS score < 28 since Fu et al. teaches such patients as excluded from eligibility for esketamine treatment. Although Applicant’s Affidavit, filed 06/24/2025, demonstrates that the administration of 60 mg of esketamine reduced the MADRS score of patients having a MADRS score of ≥ 28 , such a method of treatment is still rendered obvious by the teachings of the prior art. Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph). Fu et al. teaches a patient population wherein the mean MADRS score is 41.3 reads on the limitation of a MADRS score of at least 28 and supports the fact that a higher score equates to disease severity (see Table 1). Given that Schumann et al. teaches oral administration of 60 mg of esketamine as an effective treatment for MDD (see abstract; col. 7, lines 51-54), one of ordinary skill in the art would have a reasonable expectation of success in treating MDD patients with a MADRS score of at least 28 by orally administering 60 mg of esketamine.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,865,088 in view of Fu et al. (Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation with Intent: Double-Blind, Randomized Study (ASPIRE I), J. Clin. Psychiatry, 2020, 81(3), pp. e1-e9).
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims both recite similar methods of treating major depressive disorder comprising administering esketamine. U.S. Patent No. 11,865,088 recites a method of treating major depressive disorder comprising orally administering a dosage between 20 mg and 40 mg of esketamine for at least 28 days.
U.S. Patent No. 11,865,088 does not explicitly recite a dosage of 60 mg of esketamine. U.S. Patent No. 11,865,088 does not teach administering esketamine if the patient is determined to have a MADRS score of at least 28.
Fu et al. is drawn towards the use of an esketamine nasal spray for the treatment of MDD symptoms (see abstract). Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph).
It would have been obvious to one of ordinary skill in the art to administer esketamine if the patient is determined to have a MADRS score of at least 28, as suggested by Fu et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fu et al. teaches a MADRS greater than 28 as an eligibility criterion, and that MDD patients with a higher MADRS score favor esketamine, with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to treat major depressive disorder comprising administering esketamine, as suggested by U.S. Patent No. 11,865,088, and produce the instant invention. One of ordinary skill in the art would have been motivated to do so since U.S. Patent No. 11,865,088 does disclose an overlapping method of treatment, with a reasonable expectation of success absent evidence of criticality of the particular steps.
With regards to the limitation claimed in instant claim 1, which claims 60 mg of esketamine, U.S. Patent No. 11,865,088 does not specifically teach the exact amounts claimed in instant claim 1. However, it would be within the skill of an ordinary artisan to be able to modify the dosage in order to obtain the desired bioavailability of the agent. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,253,487 in view of Fu et al. (Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation with Intent: Double-Blind, Randomized Study (ASPIRE I), J. Clin. Psychiatry, 2020, 81(3), pp. e1-e9).
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims both recite similar methods of treating major depressive disorder comprising administering esketamine. U.S. Patent No. 11,253,487 recites a method of treating major depressive disorder comprising orally administering a dosage of 40 mg of esketamine for at least 28 days.
U.S. Patent No. 11,253,487 does not explicitly recite a dosage of 60 mg. U.S. Patent No. 11,253,487 does not teach administering esketamine if the patient is determined to have a MADRS score of at least 28.
Fu et al. is drawn towards the use of an esketamine nasal spray for the treatment of MDD symptoms (see abstract). Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph).
It would have been obvious to one of ordinary skill in the art to administer esketamine if the patient is determined to have a MADRS score of at least 28, as suggested by Fu et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fu et al. teaches a MADRS greater than 28 as an eligibility criterion, and that MDD patients with a higher MADRS score favor esketamine, with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to treat major depressive disorder comprising administering esketamine, as suggested by U.S. Patent No. 11,253,487, and produce the instant invention. One of ordinary skill in the art would have been motivated to do so since U.S. Patent No. 11,253,487 does disclose an overlapping method of treatment, with a reasonable expectation of success absent evidence of criticality of the particular steps.
With regards to the limitation claimed in instant claim 1, which claims 60 mg of esketamine, U.S. Patent No. 11,253,487 does not specifically teach the exact amounts claimed in instant claim 1. However, it would be within the skill of an ordinary artisan to be able to modify the dosage in order to obtain the desired bioavailability of the agent. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,016,832 in view of Fu et al. (Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation with Intent: Double-Blind, Randomized Study (ASPIRE I), J. Clin. Psychiatry, 2020, 81(3), pp. e1-e9).
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims both recite similar methods of treating major depressive disorder comprising administering esketamine. U.S. Patent No. 12,016,832 recites a method of treating major depressive disorder comprising orally administering a dosage of 40 mg of esketamine for at least 28 days.
U.S. Patent No. 12,016,832 does not explicitly recite a dosage of 60 mg. U.S. Patent No. 12,016,832 does not teach administering esketamine if the patient is determined to have a MADRS score of at least 28.
Fu et al. is drawn towards the use of an esketamine nasal spray for the treatment of MDD symptoms (see abstract). Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph).
It would have been obvious to one of ordinary skill in the art to administer esketamine if the patient is determined to have a MADRS score of at least 28, as suggested by Fu et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fu et al. teaches a MADRS greater than 28 as an eligibility criterion, and that MDD patients with a higher MADRS score favor esketamine, with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to treat major depressive disorder comprising administering esketamine, as suggested by U.S. Patent No. 12,016,832, and produce the instant invention. One of ordinary skill in the art would have been motivated to do so since U.S. Patent No. 12,016,832 does disclose an overlapping method of treatment, with a reasonable expectation of success absent evidence of criticality of the particular steps.
With regards to the limitation claimed in instant claim 1, which claims 60 mg of esketamine, U.S. Patent No. 12,016,832 does not specifically teach the exact amounts claimed in instant claim 1. However, it would be within the skill of an ordinary artisan to be able to modify the dosage in order to obtain the desired bioavailability of the agent. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,957,645 in view of Fu et al. (Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation with Intent: Double-Blind, Randomized Study (ASPIRE I), J. Clin. Psychiatry, 2020, 81(3), pp. e1-e9).
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims both recite similar methods of treating major depressive disorder comprising administering esketamine. U.S. Patent No. 11,957,645 recites a method of treating major depressive disorder comprising orally administering a dosage between 15 ng/mL and 30 ng/mL of esketamine for at least 28 days.
U.S. Patent No. 11,957,645 does not explicitly recite a dosage of 60 mg. U.S. Patent No. 11,957,645 does not teach administering esketamine if the patient is determined to have a MADRS score of at least 28.
Fu et al. is drawn towards the use of an esketamine nasal spray for the treatment of MDD symptoms (see abstract). Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph).
It would have been obvious to one of ordinary skill in the art to administer esketamine if the patient is determined to have a MADRS score of at least 28, as suggested by Fu et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fu et al. teaches a MADRS greater than 28 as an eligibility criterion, and that MDD patients with a higher MADRS score favor esketamine, with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to treat major depressive disorder comprising administering esketamine, as suggested by U.S. Patent No. 11,957,645, and produce the instant invention. One of ordinary skill in the art would have been motivated to do so since U.S. Patent No. 11,957,645 does disclose an overlapping method of treatment, with a reasonable expectation of success absent evidence of criticality of the particular steps.
With regards to the limitation claimed in instant claim 1, which claims 60 mg of esketamine, U.S. Patent No. 11,957,645 does not specifically teach the exact amounts claimed in instant claim 1. However, it would be within the skill of an ordinary artisan to be able to modify the dosage in order to obtain the desired bioavailability of the agent. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 1-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/504,388 (reference application) in view of Fu et al. (Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation with Intent: Double-Blind, Randomized Study (ASPIRE I), J. Clin. Psychiatry, 2020, 81(3), pp. e1-e9).
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims both recite similar methods of treating major depressive disorder comprising administering esketamine. U.S. Application No. 18/504,388 recites a method of treating major depressive disorder comprising orally administering a dosage between 15 ng/mL and 30 ng/mL of esketamine for at least 28 days.
U.S. Application No. 18/504,388 does not explicitly recite a dosage of 60 mg. U.S. Application No. 18/504,388 does not teach administering esketamine if the patient is determined to have a MADRS score of at least 28.
Fu et al. is drawn towards the use of an esketamine nasal spray for the treatment of MDD symptoms (see abstract). Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph). Fu et al. teaches that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph).
It would have been obvious to one of ordinary skill in the art to administer esketamine if the patient is determined to have a MADRS score of at least 28, as suggested by Fu et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fu et al. teaches a MADRS greater than 28 as an eligibility criterion, and that MDD patients with a higher MADRS score favor esketamine, with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to treat major depressive disorder comprising administering esketamine, as suggested by U.S. Application No. 18/504,388, and produce the instant invention. One of ordinary skill in the art would have been motivated to do so since U.S. Application No. 18/504,388 does disclose an overlapping method of treatment, with a reasonable expectation of success absent evidence of criticality of the particular steps.
With regards to the limitation claimed in instant claim 1, which claims 60 mg of esketamine, U.S. Application No. 18/504,388 does not specifically teach the exact amounts claimed in instant claim 1. However, it would be within the skill of an ordinary artisan to be able to modify the dosage in order to obtain the desired bioavailability of the agent. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant also argues that “Newly-cited Fu is merely representative of disclosures in the art that might suggest ketamine or esketamine could have been intravenously or intranasally administered, intermittently, to treat MDD patients, in particular, those with suicidal ideations. Nothing in Fu, or the cited documents, suggests that the magnitude of the baseline MADRS score should be used to determine an MDD patient's course of treatment. Moreover, it is surprising that such significant improvements in MADRS score would be observed in those subjects having a baseline MADRS ≥ 28. Applicant requests withdrawal of the obviousness-type double patenting rejections.” The Examiner respectfully disagrees since Fu et al. teaches eligibility criteria of the study to include having a MADRS total score greater than 28 predose on day 1 (pg. e2, left column, second paragraph), and that patients favored esketamine among patients with prior suicide attempt and more severed depressive symptoms, wherein the MADRS total score is greater than the median (pg. e4, right column, first paragraph). One of ordinary skill in the art would thus expect that esketamine administration can significantly improve depression severity based on a MADRS score greater than 28, with a reasonable expectation of success absent evidence of criticality of the particular steps. Additionally, one of ordinary skill in the art would have been motivated to not administer esketamine to a patient having a MADRS score < 28 since Fu et al. teaches such patients as excluded from eligibility for esketamine treatment. Thus, the obviousness-type double patenting rejections are maintained.
Conclusion
Claims 1-21 are rejected.
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.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691