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 .
Election/Restrictions
Applicant's election with traverse of the following species:
Racemic ketamine as the elected single rapid-acting antidepressant species
Major depressive episode as the elected mood disorder species. Acknowledge is made that the elected major depressive episode is a species of major depressive disorder.
Human subject has a history of non-response to at least one prior antidepressant therapy as the elected human subject species.
Intravenous route as the elected route of administration species.
Co-formulate as a pharmaceutical composition as the elected formulation species
are maintained.
Claims 5-6, 9 and 17 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Priority
The instant application 18/749,726 filed on June 21, 2024 is a continuation of U.S. Application No. 18/483,225 filed on October 9, 2023, which claims priority to, and the benefits of a divisional of U.S. Application No. 18/049,589 filed on October 25, 2022 (now issued as U.S Patent No. 11,793,794 B2 Published on October 24, 2023), which is a continuation of U.S. Application No. 17/269,470 filed on February 18, 2021 (now issued as U.S. Patent No. 12,090,145 B2 Published on September 17, 2024), which is a 371 of PCT/US2019/047288 filed on August 20, 2019 that claims priority, and the benefits of U.S. Provisional Application No. 62/719,935 filed on August 20, 2018.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on February 20, 2026, wherein claims 1, 4-9, 20, 22, 25, 27 and 30-31 are amended; claims 10, 15-19, 23-24 and 28-29 are unchanged; claims 32-38 are newly added; and claims 2-3, 11-14, 21 and 26 are cancelled.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4-10, 15-20, 22-25 and 28-38 are pending. Claims 5-6, 9 and 17 remain withdrawn.
Claims 1, 4, 7-8, 10, 15-16, 18-20, 22-25, and 27-38 are under examination in accordance with the elected species along with the expanded compound set forth in the Expansion of Species section above.
Action Summary
Claims 1-4, 7-8, 10-16, 18-20, 22-25, and 27-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification while being enabling for treating and ameliorating major depressive disorder by administering 6 mg of oral rapamycin 2 hours prior to administering 0.5 mg/kg of intravenous ketamine once every 2 weeks to the extent that treating does not include preventing, does not reasonably provide enablement for treating or ameliorating the entire scope of a mood disorder in a human subject in need thereof comprising administering any therapeutically effective amount of any rapid-acting antidepressant once every two weeks and a dose of 0.5 mg to 15 mg of temsirolimus, such that the term “treating” includes preventing are withdrawn in light of the claim amendments.
Claim 8 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 is withdrawn in light of the claim amendment.
Claims 3 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends are withdrawn in light of the claim amendments. Said claim has been cancelled.
Claims 1-4, 7-8, 10-13, 15-16, 18-20 and 28-31 rejected under 35 U.S.C. 103 as being unpatentable over Medeiros da Frota Ribeiro et al. (Curr Psychiatry Rep. 2017;19(12):107), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Bellmunt et al. (Ann Oncol, 2008. Vol. 19(8): 1387-1392), as evidenced by Andrade (The Journal of Clinical Psychiatry, 2017. Vol. 78, 6: e674-e677; cited in the IDS filed on August 8, 2024) are withdrawn in light of the claim amendments, because the instant independent claims combine multiple limitations from the dependent claims that changes the scope of the claims.
Claims 1-4, 7-8, 10-16, 18-20, 22-25, and 27-31 are rejected under 35 U.S.C. 103 as being unpatentable over Medeiros da Frota Ribeiro et al. (Curr Psychiatry Rep. 2017;19(12):107), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Bellmunt et al. (The Science of the total environment, 2013. Vol. 443: 324-37) as applied to claims 1-4, 7-8, 10-13, 15-16, 18-20 and 28-31 above, and further in view of Di et al. (“Chapter 41: Formulation” in: Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization. 2nd ed. San Diego, CA, USA: Elsevier Science, 2016: 497-510) are withdrawn in light of the claim amendments, because the instant independent claims combines multiple limitations from the dependent claims that changes the scope of the claims.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/5/2026 was filed after the mailing date of the Non-Final Office Action on October 21, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention (newly applied as necessitated by amendment).
Amended claim 8 recites the limitation of “the human subject with MDD experiences a major depressive episode”. There is insufficient written basis for the human subject with MDD experiences a major depressive episode in the specification.
The specification only describes “major depressive episode” in the following paragraphs (see shaded):
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(see page 9, line 19-27 of the instant specification); and
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(see e.g., p. 34, line 15-21). In other words, the specification only describes “major depressive episode” is included as part of “major depressive disorder” as one of the mood disorders. The specification does not disclose the human subject species is a human subject with MDD experiences a major depressive episode. Therefore, it is not apparent that applicant is in the possession of “the human subject with MDD experiences a major depressive episode”.
This is a new matter rejection.
Claims 1, 4, 7-8, 10, 15-16, 18-20, 22-25, and 27-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating major depressive disorder in a human subject suffering from the major depressive disorder by administering 6 mg of oral rapamycin 2 hours prior to administering 0.5 mg/kg of intravenous ketamine once every 2 weeks, does not reasonably provide enablement for treating the entire scope of mood disorder instantly claimed (i.e., “major depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder”) in a human subject suffering from said mood disorder comprising administering any therapeutically effective amount of each and every species of RAAD (i.e., “racemic ketamine, (R)-ketamine, or (S)-ketamine”) intravenously once every two weeks and a dose of 0.5 mg to 15 mg of temsirolimus intravenously. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims (newly applied as necessitated by amendment).
Attention is directed to in re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and, (8) the quantity of experimentation necessary. All of the Wands factors have been considered and discussed below:
(1, 5) The breadth of the claims and the Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
Instant claim 1 recites “[a] method for treating a mood disorder in a human subject suffering from the mood disorder, the method comprising: administering to the human subject a therapeutically effective amount of: a) a rapid-acting antidepressant (RAAD) or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof, wherein the RAAD is administered once every two weeks, wherein the RAAD is racemic ketamine, (R)-ketamine, or (S)-ketamine, and wherein the RAAD is administered to the human subject intravenously; and b) temsirolimus, or a pharmaceutically acceptable salt, solvate, enantiomer, or tautomer thereof, or mixtures thereof, wherein the temsirolimus is administered to the human subject at a dose of 0.5 mg to 15 mg, and wherein the temsirolimus is administered to the human subject intravenously; thereby treating the mood disorder, wherein the mood disorder is selected from the group consisting of major depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder”.
Instant claim 30 recites “[a] method for treating a mood disorder in a human subject suffering from the mood disorder, the method comprising: administering to the human subject a therapeutically effective amount of: a) a rapid-acting antidepressant (RAAD) or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof, wherein the RAAD is racemic ketamine, (R)-ketamine, or (S)-ketamine, and wherein the RAAD is administered to the human subject intravenously; and b) temsirolimus, or a pharmaceutically acceptable salt, solvate, enantiomer, or tautomer thereof, or mixtures thereof, wherein the temsirolimus is administered to the human subject at a dose of 0.5 mg to 5 mg, and wherein the temsirolimus is administered to the human subject intravenously; thereby treating the mood disorder, wherein the mood disorder is selected from the group consisting of major depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder”.
The breadth of the claims covers administering any therapeutically effective amount of each and every species of rapid-acting antidepressant (i.e., “racemic ketamine, (R)-ketamine, or (S)-ketamine”) or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof intravenously once every two weeks; and 0.5-15 mg or 0.5-5 mg of intravenous temsirolimus, or a pharmaceutically acceptable salt, solvate, enantiomer, or tautomer thereof, or mixtures thereof for treating each and every species of mood disorder (i.e., “depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder) in a human subject suffering from said mood disorder.
(2, 3, 4) The state of the prior art, the level of skill in the art, and the predictability or lack
thereof in the art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the
art would have known, at the time the application was filed, about the subject matter to which the
claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art
refers to the skill of those in the art in relation to the subject matter to which the claimed invention
pertains at the time the application was filed.”
At the time the application was filed, one skilled in the art would have known that ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, is the prototype rapid-acting antidepressant with multiple clinical trials supporting its robust effects in major depressed patients, as evidenced by Zanos et al. (CNS Drugs, 2018. Vol. 32(3): 197–227; cited in the previous Office Action) (see e.g., p. 5, second paragraph). Additionally, one skilled in the art would have also known that temsirolimus, which is a novel water-soluble rapamycin analog, can successfully reduce depression-related immobility in ICR mice that are routinely utilized in modeling depression, as evidenced by Kara et al. (Behav Pharmacol, 2018. Vol. 29(4):379-384; cited in the previous Office Action) (see e.g., p. 380, left column, 1st paragraph).
Iadarola et al. (Ther Adv Chronic Dis, 2015. Vol. 6(3): 97-114) reviews ketamine in the treatment of depression (see e.g., title). Iadarola et al. teaches rapid antidepressant-like behaviors in rodents were only observed following treatment with low doses ketamine (10–20 mg/kg) as opposed to higher anesthetic doses (80 mg/kg), suggesting an inverted ‘U’ dose-effect relationship (see e.g., p. 106, left column, line 17-22). In other words, at the time the application was filed, one skilled in the art would have known ketamine exhibits “U” shaped dose-effect relationship for its antidepressant effects, and higher dosage does not necessarily lead to the desired therapeutic outcomes of treating depression. Therefore, the cited reference demonstrate it is highly unpredictable that any therapeutically effective amount of the claimed rapid-acting antidepressant and 0.5mg-5 mg or 0.5 mg-5mg of temsirolimus can successfully treat the entire scope of mood disorder instantly claimed.
According to Yang et al. (Biological Psychiatry, 2018. Vol. 83, 1: 18-28), the study aimed to examine whether mTOR signaling and/or ERK signaling play a role in the mechanism underlying the anti-depressant actions of (R)-ketamine and (S)-ketamine in a chronic social defeat stress (CSDS) model of depression reported that the mTOR inhibitors (rapamycin and AZD8005) block the antidepressant effects of (S)-ketamine in a chronic social defeat stress (CSDS) model of depression, but not (R)-ketamine (see e.g., abstract; p. 19, left column, 3rd paragraph). In other words, one skilled in the art would have known that mechanistic target of rapamycin (mTOR) plays a role in the antidepressant effects of (S)-ketamine; and therefore, the cited reference demonstrates it is highly unpredictable that any therapeutically effective amount of each and every rapid-acting antidepressant, including (S)-ketamine; and 0.5mg-5 mg or 0.5 mg-5mg of temsirolimus can treat the entire scope of mood disorder instantly claimed.
Du et al. (Front Psychiatry, 2022. Vol. 13: 813103.) reviews the use of ketamine for the treatment of post-traumatic stress disorder (PTSD) among soldiers with combating experience. Du et al. teaches the available evidence showed no significant difference in the incidence of PTSD between combatant soldiers on the battlefield with or without ketamine treatment, and concludes ketamine was not effective on lower the PTSD incidence for soldiers on the battlefield, nor on the PTSD-scale scores in early PTSD patients (see e.g., abstract). In other words, the cited reference demonstrates it is highly unpredictable that any therapeutically effective amount of each and every rapid-acting antidepressant, including (S)-ketamine; and 0.5mg-5 mg or 0.5 mg-5mg of temsirolimus can treat the entire scope of mood disorder, including post-traumatic stress disorder, in any human subject suffering from said mood disorder.
While the administration of 0.5 mg/kg of intravenous racemic ketamine and 6 mg of oral rapamycin may play a role in treating major depressive disorder in a subject suffering from said disorder based on Example 1 of instant specification, it is uncertain whether administering any therapeutically effective amount of each and every species of rapid-acting antidepressant (i.e., “racemic ketamine, (R)-ketamine, or (S)-ketamine”) or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof intravenously once every two weeks; and 0.5 mg-15 mg or 0.5 mg-5 mg of intravenous temsirolimus, or a pharmaceutically acceptable salt, solvate, enantiomer, or tautomer thereof, or mixtures thereof can successfully treat each and every species of mood disorder (i.e., “depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder) in a human subject suffering from said mood disorder without undue experimentation.
(6, 7, 8) The amount of guidance given, the presence of working example and the quantitation
of experimentation required:
In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the claimed invention. In the present case, the specification discloses patients with major depression treated with a single 6 mg oral rapamycin approximately two hours prior to 0.5 mg/kg of ketamine infused intravenously over 40 minutes successfully prolong the antidepressant effects for at least 2 weeks following the treatment; and the patients completed two ketamine infusion test days separated by at least two weeks (see Example 1 of the specification). It is noted that the specification only exemplify major depression as the species of mood disorder and patients with a history of non-response to at least one prior antidepressant as the species of human subject. The specification only exemplified the method of treating using oral rapamycin and intravenous ketamine, rather than intravenous temsirolimus and intravenous ketamine. The therapeutic effect of RAAD (“racemic ketamine, (R)-ketamine, or (S)-ketamine) and temsirolimus has not been disclosed. Therefore, the quantity of experimentation necessary to carry out the claimed invention is high, because one of the relative skill in the art could not reasonably predict which mood disorders encompassed by the instant claims could be treated by administering each and every species of rapid-acting antidepressant (“racemic ketamine, (R)-ketamine, or (S)-ketamine) or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof in any therapeutically effective amount intravenously once every two weeks; and 0.5 mg-15 mg or 0.5 mg-5 mg of intravenously temsirolimus, or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof based on the limited disclosure provided.
Accordingly, while being enabling for treating major depressive disorder in a human subject suffering from the major depressive disorder by administering 6 mg of oral rapamycin 2 hours prior to administering 0.5 mg/kg of intravenous ketamine once every 2 weeks, the entire scope of clamed invention is not enabled by the instant specification. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
Response to Arguments
Applicant's arguments filed on February 20, 2026 with respect to the rejection of claims 1-4, 7-8, 10-16, 18-20, 22-25, and 27-31 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, have been fully considered but they are not persuasive for the reasons set forth below.
Applicant amends claims 1 and 30 from the recitation of “[a] method for treating or ameliorating a mood disorder in a human subject in need thereof” to the recitation of “[a] method for treating a mood disorder in a human subject suffering the mood disorder”, such that the method for treating or ameliorating does not encompass prophylaxis and a subject without the mood disorder. Applicant further amends the scope of RAAD in claims 1 and 30 by adding the limitation of “wherein the RAAD is racemic ketamine, (R)-ketamine, or (S)-ketamine”, previously found in claim 2 (now cancelled); and the limitation of “and wherein the RAAD is administered to the human subject intravenously”, previously found in claim 12 (now cancelled). Applicant further amends the scope of temsirolimus in claims 1 and 30 by adding the limitation of “wherein the temsirolimus is administered to the human subject intravenously”, previously found in claim 14 (now cancelled). Applicant further amends the scope of mood disorder in claims 1 and 30 by adding the limitation of “wherein the mood disorder is selected from the group consisting of major depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder”, previously found in claim 7 (now amended). It is noted that the instant independent claims combines multiple limitations from the dependent claims. Each of these findings demonstrate the claim amendment filed on February 20, 2026 changes the scope of the claims, and that necessitates a new ground of rejection on the record.
In Summary, applicant noted the enablement rejection with respect to “each and every rapid-acting antidepressant” and “preventing” are moot in light of the claim amendments. Applicant argues the claimed invention are described in the manner that permits one of ordinary skill in the art to practice the entire scope of the amended claims without undue experimentation. Applicant further argues the mere fact that experiment might be required is insufficient to support the enablement rejection; even if experimentation might be required, it would not be undue. Applicant further argues the level of ordinary skill in the relevant art, the scope of which is not address in the Office Action, is relatively high, which weights in favor of enablement.
In response, applicant’s argument is not found persuasive. The Examiner clearly meets the burden of establishing a reasonable basis to question the enablement provided for the claimed invention. The Examiner has established the state of the prior art by citing references to address what one skilled in the art would have known, at the time the application was filed, about the NMDAR antagonist ketamine and temsirolimus, respectively. The previous rejection on the record also provides references establishing the unpredictability in the art as to why the relative skill of those in the art is low for using of each and every NMDAR antagonist as the rapid-acting antidepressant for treating, ameliorating the entire scope of mood disorder to the extent that treating and ameliorating includes prophylaxis in light of the special definition in the specification. The previous rejection on the record also established that a person skilled in the art would have known rapid-acting antidepressants do not exert antidepressant effect regardless of the route of administration. The examiner is not required to prove that every species encompassed by the claimed invention is non-enable in order to establish the enablement rejection. Therefore, applicant’s assertion that any person skilled in the art to can practice the entire scope of the claimed invention without undue experimentation is not found persuasive.
Given that the claim amendments change the scope of the claims, it necessitates a new ground of rejection for the reasons set forth herein.
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.
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. Applicant is 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, 4, 7-8, 10, 15-16, 18-20, 22-25, and 27-38 are rejected under 35 U.S.C. 103 as being unpatentable over Medeiros da Frota Ribeiro et al. (Curr Psychiatry Rep. 2017;19(12):107), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31), Qi et al. (J Neurol Neuromedicine, 2016. Vol. 1(4): 21-24), Bellmunt et al. (Ann Oncol, 2008. Vol. 19(8): 1387-1392), and Di et al. (“Chapter 41: Formulation” in: Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization. 2nd ed. San Diego, CA, USA: Elsevier Science, 2016: 497-510), as evidenced by Andrade (The Journal of Clinical Psychiatry, 2017. Vol. 78, 6: e674-e677; cited in the IDS filed on August 8, 2024) (newly applied as necessitated by amendment).
Please note each of these prior arts and evidentiary reference are cited in the previous Office Actions.
Medeiros da Frota Ribeiro et al. teaches a patient diagnosed with major depressive disorder presented with depression and suicidal ideation was started on ketamine infusions at a standard dose of 0.5 mg/kg over 40 minutes. Please note the ketamine taught by Medeiros da Frota Ribeiro et al. is a racemic mixture of the enantiomers (R)-ketamine and (S)-ketamine, as evidenced by Andrade; and a NMDA receptor modulator. Please also note the patient taught by Medeiros da Frota Ribeiro et al. is a human subject. Please also note the ketamine infusion taught by Medeiros da Frota Ribeiro et al. is administered intravenously. Medeiros da Frota Ribeiro et al. further teaches the infusions were well tolerated, and the patient’s Quick Inventory of Depressive Symptomatology (also referred to therein as “QIDS-SR”) score decreased from 20 to 6 after six infusions. Medeiros da Frota Ribeiro et al. further teaches after 11 weeks, the patient had received a total of 13 infusions initially biweekly then once every 2 weeks, and her QIDS-SR remained in the low range (6 points) (see e.g., p. 107, “Case 2”; Fig. 1). Medeiros da Frota Ribeiro et al. further teaches previous trials with fluoxetine, venlafaxine, desvenlafaxine, duloxetine, and lurasidone were of limited efficacy; and the patient had experienced approximately one depressive episode yearly with an usual duration of 1 month since her young adulthood (see e.g., p. 107; “Case 2”).
Medeiros da Frota Ribeiro et al. does not teach temsirolimus is administered to the human subject at a dose of 0.5 mg to 15 mg.
Kara et al. teaches autophagy enhancer temsirolimus injected intraperitoneally to ICR mice at a dose of 5 or 10 mg/kg and 10 ml/kg volume once daily for 4 days caused an antidepressant-like effect (reduced immobility) in the forced-swim test (see e.g., p. 382, “Results”, “Experiment 2: temsirolimus in ICR mice”; Table 2). Kara et al. further teaches the ICR (CD-1) mice are routinely utilized in modeling depression (see e.g., p. 380, left column, line 13-16). Kara et al. further teaches these data support the notion that enhancing autophagy may have mood-stabilizing effects (see e.g., abstract). Please note intraperitoneal administration of temsirolimus as taught by Kara et al. is the peritoneal administration as claimed in claim 13. Kara et al. further teaches temsirolimus induces severe toxic effects including increased susceptibility to infections because of their immunosuppressant properties, thrombocytopenia, anemia, fever, pain, increased plasma creatinine levels, hypertension, hypercholesterolemia and hypertriglyceridemia, peripheral edema, constipation, diarrhea and nausea (see e.g., p. 383, left column, 2nd paragraph).
Qi et al. teaches even though the mechanism associated with the pathogenesis of major depressive disorder have yet to be completely understood, animal models are predictive of antidepressant activity, especially the force swim test (FST) is one of the most widely used test across laboratories for accessing symptoms of depression (see e.g., page 21, “Introduction” section). Qi et al. further teaches strain is one of the most important parameters to consider in the FST, including outbred strains (Swiss-Webster, CD-1, CF-1, NIH Swiss, NMRI, etc.), wherein CD-1 is one of the most frequently used out strain that respond positively to most of the antidepressant when subject to the FST (see e.g., p. 22, “strain” section, 1st paragraph). Qi et al. further teaches ICR mice also provide opportunities for identifying drugs that are effective in patients with drug-resistant depression (see e.g., p. 23, left column, “conclusion” section, 2nd paragraph).
Nair et al. teaches a method of converting doses between species, including mouse to human, shown below (see e.g., Table 1):
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.
Bellmunt et al. teaches dosage interruption and medication guidelines are available for cases of grade 3-4 adverse events (AEs) in human subjects treated with temsirolimus that do not resolve with medical management or supportive care. Bellmunt et al. further teaches temsirolimus should be held if the absolute neutrophil count is <1000/µl, the platelet count is <75 000/µL, or a grades 3-4 AE occurs. Once toxic effects have resolved to grade 2 or lower, temsirolimus may be restarted with the dose reduced by 5 mg/week to no lower than 15 mg/week. Concomitant use of strong CYP3A4 inhibitors should be avoided because of increased potential for temsirolimus-related side-effects, but a temsirolimus dose reduction to 12.5 mg/week is recommended if coadministration is necessary (see e.g., abstract; p. 1390, right column, 3rd paragraph).
Di et al. teaches intravenous has rapid onset and complete bioavailability as it precisely delivers the complete dose (see e.g., p. 498, “41.2.2 Intravenous (IV)” section). Di et al. further teaches intraperitoneal injection is particularly useful in discovery laboratories for small animal studies, where it is often preferred over IV due to ease of administration (see e.g., 498, “41.2.3 Intraperitoneal [IP]). Di et al. further teaches intraperitoneal bypass first-pass metabolism from the gut, but is still subject to first-pass metabolism by the liver, since absorption is via the portal system (see e.g., p. 499, line 1-2).
In short, Medeiros da Frota Ribeiro et al. clearly teaches intravenous administration of ketamine at a standard dose of 0.5 mg/kg, including the frequency of once every 2 weeks, can successfully improves QIDS-SR and depressive symptomatology score in a human subject diagnosed with major depressive disorder. The difference between the method of Medeiros da Frota Ribeiro et al. and the claimed method is that the prior art does not teach the administration of temsirolimus at dose of 0.5 mg to 15 mg or 0.5 mg to 5 mg; However, Kara et al. teaches temsirolimus injected intraperitoneally at the dose of 5 mg/kg can cause antidepressant effect in the ICR (CD-1) mouse model for depression; Qi et al. teaches the ICR(CD-1) mouse is an animal strain that can be used in behavior test, such as forced swim test, as a model for mimicking major depressive disorder in human to assess antidepressant efficacy; and Nair et al. teaches the conversion factor to convert animal dose (mouse) to human equivalent dose. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by combining the method of Medeiros da Frota Ribeiro et al. (0.5 mg/kg intravenous ketamine, once every two weeks) with the method of Kara et al. (temsirolimus) at the human equivalent dose taught by Nair et al., then optimize said human equivalent dose to include the claimed dose through routine experimentation as taught by Bellmunt et al., and then substituting intraperitoneal administration with intravenous administration as taught by Di et al. for treating major depressive disorder in a human subject, as taught by Qi et al. For instance, if a human subject weights 60 kg and temsirolimus administered at the lowest effective dose of 5 mg/kg taught by Kara et al.:
5
m
g
k
g
×
0.081
×
60
k
g
=
24.3
m
g
, the mouse dosing taught by Kara et al. is equivalent to a human equivalent dose of 24.3 mg. One would have been motivated to combine in order to from a third method to be used for treating major depressive disorder in the same subject species (human), because the ICR(CD-1) mouse model of Kara is a model of major depressive disorder as taught by Qi et al. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One would have also been motivated to optimize the dose of temsirolimus and the route of administration, because Kara et al. teaches temsirolimus induces severe toxic effects, including increased susceptibility to infections and thrombocytopenia; Bellmunt et al. teaches temsirolimus-related adverse events and side effects can be managed by reducing the dose; and Di et al. teaches intraperitoneal administration is still subject to first-pass metabolism by the liver, and intravenous route enables precise delivery of complete dose due to its complete bioavailability. One would have a reasonable expectation of success to arrive at the claimed invention including the claimed dose through routine optimization, because one would have reasonably expected that by reducing the dose of temsirolimus starting from the lowest effective human-equivalent dose (24.3 mg, see calculation shown above) would successfully prevent adverse side effects of temsirolimus in a human subject; and substituting intraperitoneal temsirolimus with intravenous would successfully deliver the complete dose ; and therefore, by combing the method of Medeiros da Frota Ribeiro et al. with the method of Kara et al. in view of Nair et al., Qi et al., Bellmunt et al., and Di et al. would reasonably expected to be similarly useful for treating major depressive disorder in the human 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).
Regarding the limitation of ”the human subject with MDD experiences a major depressive episode” in claim 8 and claim 36, the limitation is drawn to the subject in the method claims. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to treat a human subject with MDD experiences a major depressive episode in the method of Medeiros da Frota Ribeiro et al., Kara et al., Qi et al., Nair et al., and Bellmunt et al., Di et al. as set forth above. One would have been motivated to do so, because Medeiros da Frota Ribeiro et al. teaches the patient with MDD had experienced approximately one depressive episode yearly with an usual duration of 1 month. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the method of Medeiros da Frota Ribeiro et al., Kara et al., Qi et al. Nair et al., Bellmunt et al. and Di et al. as set forth above when successfully treat major depressive disorder itself in a human subject, the major depressive episode caused by major depressive disorder would necessarily be treated; and that render obvious the limitation instantly claimed.
Regarding the limitation of “wherein the human subject has a history of inadequate response to at least one prior antidepressant therapy” in claims 10, 24-25, and 36, the limitation is drawn to the subject in the method claims. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to treat a human subject with a history of inadequate response to fluoxetine in the method of Medeiros da Frota Ribeiro et al., Kara et al., Qi et al., Nair et al., and Bellmunt et al., Di et al. as set forth above. One would have been motivated to do so, because Medeiros da Frota Ribeiro et al. teaches ketamine improves depressive symptomatology score in a human subject with previous fluoxetine trial for depression with limited efficacy, which is an antidepressant; and Qi et al. teaches the ICR mice, which is used in the method of Kara et al., provides opportunities for identifying drugs that are effective in patients with drug-resistant depression. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the method of Medeiros da Frota Ribeiro et al., Kara et al., Nair et al., Qi, Bellmunt et al. and Di et al. as set forth above would successfully treat major depressive disorder in a human subject with a history of inadequate response to antidepressant.
Regarding the limitation of “wherein the RAAD and the temsirolimus are co-administered to the human subject” in claims 15 and 37, and the limitation of “wherein the RAAD and the temsirolimus are co-formulated as a pharmaceutical composition” in claims 16 and 38, the instant situation is amenable to the type of analysis set forth in Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) and also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946), where the court found that the selection of any order of performing process steps is prima facia obvious in the absence of new or unexpected results. As such, applying the same logic to the instant process claims, one of ordinary skill in the art would have a reasonable expectation of success to arrive at the claim invention, because one would have reasonably expected that by co-administering and/or co-formulating the racemic ketamine of Medeiros da Frota Ribeiro et al. and temsirolimus of Kara et al. in the method of Medeiros da Frota Ribeiro et al., Kara et al., Nair et al., Qi et al., Bellmunt et al. and Di et al. set forth above would successfully treat major depressive disorder.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on February 20, 2026 with respect to the rejection of claims 1-4, 7-8, 10-13, 15-16, 18-20 and 28-31 under 35 U.S.C. 103 as being unpatentable over Medeiros da Frota Ribeiro et al. (Curr Psychiatry Rep. 2017;19(12):107), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) and Bellmunt et al. (Ann Oncol, 2008. Vol. 19(8): 1387-1392), as evidenced by Andrade (The Journal of Clinical Psychiatry, 2017. Vol. 78, 6: e674-e677; cited in the IDS filed on August 8, 2024) have been fully considered but are moot, because the claim amendment changes the scope of the claims and necessitated the new ground of rejection set forth herein.
Applicant's arguments filed on September 19, 2025 with respect to the rejection of claims 1-4, 7-8, 10-16, 18-20, and 22-25 under 35 U.S.C. 103 as being unpatentable over Singh et al. (The American journal of psychiatry, 2016. Vol. 173(8): 816–826), in view of Kara et al. (Behavioural Pharmacology. Vol. 29, no. 4: 379-384. Published on June 2018), and Nair et al. (J Basic Clin Pharm., 2016. Vol. 7(2): 27-31) as applied to claims 1-4, 7-8, 10-13, 15-16 and 18-20 above, and further in view of Di et al. (“Chapter 41: Formulation” in: Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization. 2nd ed. San Diego, CA, USA: Elsevier Science, 2016: 497-510) have been fully considered but they are not found persuasive. Given that the claim amendment changes the scope of the claims, it necessitates the new ground of rejection set forth herein.
Applicant amends claims 1 and 30 from the recitation of “[a] method for treating or ameliorating a mood disorder in a human subject in need thereof” to the recitation of “[a] method for treating a mood disorder in a human subject suffering the mood disorder”, such that the method for treating or ameliorating does not encompass prophylaxis and a subject without the mood disorder. It is noted that the human subject has to be a human subject suffering the mood disorder instantly claimed. Applicant further amends the scope of RAAD in claims 1 and 30 by adding the limitation of “wherein the RAAD is racemic ketamine, (R)-ketamine, or (S)-ketamine”, previously found in claim 2 (now cancelled); and the limitation of “and wherein the RAAD is administered to the human subject intravenously”, previously found in claim 12 (now cancelled). Applicant further amends the scope of temsirolimus in claims 1 and 30 by adding the limitation of “wherein the temsirolimus is administered to the human subject intravenously”, previously found in claim 14 (now cancelled). Applicant further amends the scope of mood disorder in claims 1 and 30 by adding the limitation of “wherein the mood disorder is selected from the group consisting of major depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder”, previously found in claim 7 (now amended). It is noted that the instant independent claims combines multiple limitations from the dependent claims, which are introduced separately rather than all of them together. Each of these findings demonstrate the claim amendment filed on February 20, 2026 changes the scope of the claims, and that necessitates a new ground of rejection on the record.
In Summary, applicant argues the claim amendments overcomes the rejection of claims 1-4, 7-8, 10-13, 15-16, 18-20 and 28-31. Applicant further argues the human equivalent dose calculated from the animal dosing taught by Kara et al. (i.e., a dose of 5 mg/kg) is 24.3 mg/kg, and there is a huge gap between the dose of "0.5 mg to 15 mg” instantly claimed. Applicant argues one would not find it obvious to reduce the human equivalent dose to prevent side effects, because the drug must be therapeutically effective and have tolerable or no side-effects; and therefore, by reducing the dose below an art-taught lower therapeutic limit in the hope of reducing side effects, it would have no side effects and no therapeutic efficacy for treating the mood disorder. Applicant further argues the teachings of Kara et al. as indicated in the previous reply:
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clearly advise one would not use rapamycin or temsirolimus clinically, and that is not a disclosed examples nor preferred embodiments of Kara et al.; therefore, based on that teachings of Kara et al., it constitutes a teachings away from using rapamycin or temsirolimus. Applicant further argues the claimed dosing ranges of temsirolimus is based on improper hindsight, because the claimed invention demonstrates unexpected results by directing attention to Example 1, which shows subject received rapamycin prior to ketamine reports significant reduction in their depressive symptoms as measured by MADRS when compared to placebo. Applicant further noted that the previous Office Action stated claims 28-29 are rejected in light of the standard dose of 0.5 mg/kg taught by Medeiros da Frota Ribeiro et al., and that is incorrect.
In response, applicant’s argument is not found persuasive for the reasons set forth below:
First, the Examiner has mistakenly wrote “[i]n 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). In the present case, the ketamine at a standard dose of 0.5 mg/kg taught by Medeiros da Frota Ribeiro et al. as set forth in the method above renders obvious the dosing range instantly claimed in claims 28-29” on page 20 of the Non-Final Office Action mailed on October 21, 2025. It is true that claims 28-29 are drawn to the dosing range of temsirolimus rather than ketamine; However, the standard dose of ketamine (0.5 mg/kg) taught by Medeiros da Frota Ribeiro et al. does not need to overlap with the claimed range, because it is the one instantly claimed. Prior to said paragraph, the examiner wrote “[o]ne would have a reasonable expectation of success to arrive at the claimed invention including the claimed dose through routine optimization, because one would have reasonably expected that by reducing the dose of temsirolimus starting from the lowest effective human-equivalent dose (24.3 mg, see calculation shown above) would successfully prevent adverse side effects of temsirolimus in a human subject”(see page 1, last line to page 20, line 2); and therefore, the recitation of “[i]n the present case, the ketamine at a standard dose of 0.5 mg/kg taught by Medeiros da Frota Ribeiro et al. as set forth in the method above renders obvious the dosing range instantly claimed in claims 28-29” noted above is clearly a typographical error, because only the human equivalent dose of temsirolimus calculated from the animal dosing taught by Kara et al. needs to be overlap through routine optimization.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). It may well be true that Kara et al. teaches temsirolimus is not used clinically to treat mood disorders because it induces severe toxic effects; However, just because the prior art teaches temsirolimus induce adverse effects and suggests the development of new compounds with less adverse effects, that does not mean the temsirolimus taught by Kara et al. cannot exhibits antidepressant effect as an autophagy-enhancing compound. It is further noted that the obviousness-type rejection is form on the basis that one would have a reasonable expectation of success to arrive at the claimed invention including the claimed dose through routine optimization; specifically, by reducing the human equivalent dose of temsirolimus calculated from the animal dosing taught by Kara et al. based on the teachings of Bellmunt et al. rather than using the human equivalent dose of temsirolimus calculated from the animal dosing alone.
Applicant’s assertion that one would not find it obvious to reduce the dose of temsirolimus in the hope of reducing side effects, because the drug must be therapeutically effective and have tolerable or no side-effects; and therefore, by reducing the dose below an art-taught lower therapeutic limit, it would have no side effects and no therapeutic efficacy for treating the mood disorder. It is noted applicant’s assertion that the dose reduction of temsirolimus would have no side effects and no therapeutic efficacy appears to be mere argument without supported by appropriate evidence. Solely to rebut applicant’s argument, all medicines have side effects, as evidenced by Allegaert et al. (Arch Dis Child October, 2016. Vol. 101, 10). Reducing medication dosage based on side effect is relying on well-known and routine practice in clinical settings to manage adverse reactions while attempting to maintain therapeutic efficacy, rather than in light of claimed invention. The dose reduction concept is taught by Bellmunt et al. shown below:
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(see e.g., p. 1390, right column, 3rd paragraph). In other words, one would have reasonably expected that temsirolimus toxicity taught by Kara et al. can be effectively managed through dose reduction. Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019); ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018).
Applicant’s assertion of unexpected results (“a placebo-controlled study showed that when subjects received rapamycin prior to ketamine, they continued to report significant reduction in their depressive symptoms as measured by the clinician administered Montgomery-Asberg Depression Rating Scale”, see page 15, line 9-12 of the reply filed on February 20, 2025) is not commensurate in scope with the claimed invention. Applicant argues the claimed invention demonstrates unexpected results by directing attention to Example 1 of the specification. According to page 33 of the specification (Example 1), the results were obtained by administering a single oral dose of rapamycin (6 mg) approximately 2 hours prior to 0.5 mg/kg of ketamine infused intravenously over 40 minutes (two ketamine infusion test days separated by at least two weeks) to a symptomatic antidepressant-treated patient with major depression who have a history of non-response to at least one prior antidepressant trial shown below (see shaded):
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.
In contrast, instant claims 1 and 30 are each drawn to “[a] method for treating a mood disorder in a human subject suffering from the mood disorder, the method comprising: administering to the human subject a therapeutically effective amount of: a) a rapid-acting antidepressant (RAAD) or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof…wherein the RAAD is racemic ketamine, (R)-ketamine, or (S)-ketamine, and wherein the RAAD is administered to the human subject intravenously; and b) temsirolimus, or a pharmaceutically acceptable salt, solvate, enantiomer, or tautomer thereof, or mixtures thereof, wherein the temsirolimus is administered to the human subject at a dose…, and wherein the temsirolimus is administered to the human subject intravenously; thereby treating the mood disorder, wherein the mood disorder is selected from the group consisting of major depressive disorder (MDD), persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder”. The difference between claim 1 and claim 30 is that claim 1 has the limitation of “wherein the RAAD is administered once every to weeks” and the limitation of “the temsirolimus is administered to the human subject at a dose of 0.5 mg to 15 mg” whereas claim 30 does not limit the dosing frequency of RAAD, and has the limitation of “the temsirolimus is administered to the human subject at a dose of 0.5 mg to 5 mg”. It is noted that Applicant only exemplified unexpected result using a combination species that is different than the one instantly claimed. Specifically, the unexpected result applicant relies upon administers 6 mg of oral rapamycin approximately two hours prior to 0.5 mg/kg of ketamine infused intravenously over 40 minutes to single human subject species (symptomatic antidepressant-treated patients with major depression who have a history of non-response to at least one prior antidepressant trial). Therefore, the disclosure does not provide adequate basis for concluding that similar results would be obtained for the claimed combination, which is 0.5 mg to 15 mg or 0.5 to 10 mg of intravenous temsirolimus or a pharmaceutically acceptable salt, solvate, enantiomer, or tautomer thereof, or mixture thereof with any therapeutic effective amount of intravenous rapid-acting antidepressant (“ketamine, (R)-ketamine, or (S)ketamine”). The disclosure also does not provide adequate basis for concluding that similar results would be obtained in any human subject suffering from other species of mood disorder, such as persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder.
According to MPEP 716.02(d), “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. In the present case, Example 1 of the specification does not exemplify the administration of 0.5 mg to 15 mg or 0.5 to 10 mg of intravenous temsirolimus with any therapeutic effective amount of rapid-acting antidepressant (“ketamine, (R)-ketamine, or (S)ketamine”) or a pharmaceutically acceptable salt, solvate, or tautomer thereof, or mixture thereof as encompassed by the instant claims. Furthermore, the disclosure only exemplifies a single dosing regimen of ketamine and rapamycin (6 mg of oral rapamycin administered approximately two hours prior to 0.5 mg/kg of ketamine infused intravenously over 40 minutes), and that is not commensurate in scope to include any administration order, including co-administration. The disclosure only exemplifies a single human subject species (symptomatic antidepressant-treated patients with major depression who have a history of non-response to at least one prior antidepressant trial), and that is not commensurate in scope to encompass any other human subject species, such as persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and post-traumatic stress disorder. These finding demonstrates that applicant’s assertion of unexpected results is not commensurate in scope with the claimed invention, thus, the argument is not persuasive for the reasons set forth herein.
Therefore, the rejection is withdrawn in light of the claim amendments that changes the scope of the claims; However, the new ground of rejection has been applied as necessitated by amendment for the reasons sets forth herein.
Conclusion
No claims are 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 Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628