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 without traverse of following species: “treating dysphoria in a subject suffering from postpartum depression by intramuscular administration of S-(+)-ketamine, wherein the subject is concomitantly treated with the NSAID ibuprofen and the muscle relaxant baclofen” in the reply filed on September 13, 2024 is acknowledged.
Please note Applicant elects S-(+)-ketamine, which is a species of ketamine. It is noted that the claims submitted on August 9, 2022 does not have claims drawn to the elected S-(+)-ketamine as the ketamine species, thus, the examiner limits examination to ketamine. However, to the extent that Applicant amends the claims to include the said species, it would require further search and consideration.
Please note Applicant elects ibuprofen, which is a species of NSAIDs classified as an anti-inflammatory agent. It is noted that the claims submitted on August 9, 2022 does not have claims drawn to ibuprofen as the anti-inflammatory agent species, thus, the examiner limits examination to NSAIDs. However, to the extent that Applicant amends the claims to include the said species other than ibuprofen, it would require further search and consideration.
The reply filed on September 13, 2024 is construed in light of the claims dated August 9, 2022, the Examiner has determined that (i) dysphoria is the elected postpartum related symptom species; (ii) subject suffering from postpartum depression is the elected subject species; (iii) intramuscular ketamine is the elected compound species administered to the subject; (iv) baclofen is the elected species of muscle relaxant; and (v) NSAID is the elected species of anti-inflammatory agent.
Claims 3, 11-13, and 23 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 13, 2024.
Please note the Examiner has mistakenly indicate claim 22 is withdrawn from further consideration; However, claim 22 was under examination and was rejected under 35.U.S.C as being unpatentable over Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12), in view of Lehrer et al. (Discovery medicine, 2019. Vol. 28(154): 205–212) in the Non-Final Office Action mailed on November 14, 2024 (see page 20-22 of said Action). Therefore, this Office Action has corrected this formal matter by correctly stating the withdrawn claims.
Response to Arguments
Applicant's arguments filed on May 14, 2025 with respect to the requirement for restriction/election requirement set forth in the previous Non-Final Office Action mailed on November 14, 2024 have been fully considered but they are not persuasive.
Applicant changes dependent claim 3 from the recitation of “the postpartum related symptom is hypersomnia, insomnia, difficulty in concentration, or lethargy” to the recitation of “the related symptom comprises hypersomnia, insomnia, difficulty in concentration, or lethargy”. It is noted that said claim now includes a transitional term “comprising” that is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; and that changes the scope of the claim.
In Summary, applicant argues the elected species in the previous reply filed on September 13, 2024 should be encompassed by claims 3, 22-23 and 25-26, because amended claim 3 is now drawn to “where the subject suffers from postpartum depression characterized by dysphoria in combination with hypersomnia, insomnia, difficulty in concentration, or lethargy”; claim 22 is drawn to “where the subject is concomitantly treated with the NSAID ibuprofen and the muscle relaxant baclofen (i.e., as an anti-inflammatory agent selected from NSAIDs and corticosteroids includes ibuprofen)”; claim 23 is drawn to “where the subject is concomitantly treated with the NSAID ibuprofen and the muscle relaxant baclofen and further treated with an antidepressant, or other psychiatric, or alternative medicine”; claim 25 is drawn to “where the subject suffers from postpartum depression and is the subject is breast feeding”; and claim 26 is drawn to “where the subject is treated using a regimen in which following the administration, the subject does not express breast milk for consumption by a child for a period of at least 6 hours”.
In response, applicant’s arguments are not found persuasive for the reasons set forth below:
In response to applicant’s arguments with respect to claim 3, said argument is not found persuasive because applicant changes the scope of the claim by incorporating the transitional term “comprising” that is not originally claimed. Since applicant has receive an action on the merits for the originally presented claims and elects a method of treating dysphoria as the species of “treating a postpartum related symptom” in the previous reply to the Requirement of Election/Restrictions filed on September 13, 2024, said reply does not elect the species of postpartum related symptoms in claim 3 (“hypersomnia, insomnia, difficulty in concentration, or lethargy”) in addition to the elected dysphoria.
Applicant’s argument pertaining to claim 22 is found persuasive. The Examiner noted that claim 22 was under examination and was rejected under 35.U.S.C as being unpatentable over Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12), in view of Lehrer et al. (Discovery medicine, 2019. Vol. 28(154): 205–212) in the Non-Final Office Action mailed on November 14, 2024 (see page 20-22 of said Action). Therefore, this Office Action has corrected this formal matter by correctly stating the withdrawn claims.
In response to applicant’s argument with respect to claim 23, applicant has received an action on the merits on June 17, 2024 to elect a specific subject species; However, applicant did not specifically elect a subject species that is concomitantly treated with the antidepressant, or other psychiatric, or alternative medicine.
In response to applicant’s argument with respect to claim 23, applicant has received an action on the merits on June 17, 2024 to elect a specific subject species; However, applicant did not specifically elect a subject species that is breast feeding.
In response to applicant’s argument with respect to claim 26, applicant has received an action on the merits on June 17, 2024 to elect a specific subject species; However, applicant did not specifically elect a subject species that is breast feeding and wherein following the administering, the subject does not express breast milk for consumption by a child for a period of at least 6 hours.
Therefore, claims 3, 11-13, and 23 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species for the reasons set forth herein.
Action Summary
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on May 14, 2025, wherein claims 1-4, 9, and 24 are amended; claims 5, 14-17, 21, and 25-26 are cancelled; and claims 6-8, 10-13, 18-20, and 22-23 are unchanged. Applicant’s amendment to claims 9 has overcome each and every objection previously sets forth in the Non-Final Office Action mailed on November 14, 2024. Applicant’s arguments with respect to the objection of claim 10 have been fully considered and they are persuasive; therefore, the objection to claim 10 has been withdrawn.
Acknowledgement is made of the receipt and entry of the amendment to the abstract filed on May 14, 2025. Applicant’s amendment to the abstract has overcome each and every objection previously sets forth in the Non-Final Office Action mailed on November 14, 2024.
Claim 1-2, 4-10, 18-20, 22, and 24 rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives (newly reapplied as necessitated by amendment) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claim 2 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 are withdrawn in light of the amendment; However, upon further consideration, the rejection has been reapplied as necessitated by amendment for the reasons set forth below.
Claims 4 and 9 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 are withdrawn in light of the claim amendment filed on May 14, 2025.
Claim 5 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, because the claim is cancelled in light of the claim amendment filed on May 14, 2025.
Claim 5 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 is withdrawn, because the claim is cancelled in light of the claim amendment filed on May 14, 2025.
Claims 1, 5, and 24 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12; cited under “Non-Patent Literature Documents”, cited no. M in the IDS filed on 9/13/2024) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claims 1-2, 5, and 24 rejected under 35 U.S.C. 103 as being unpatentable over Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12; cited under “Non Patent Literature Documents”, cited no. M in the IDS filed on 9/13/2024), in view of Frank et al. (Psychiatry research, 1992. Vol. 43, 3: 231–241) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claims 1, 5, 18, and 24 rejected under 35 U.S.C. 103 as being unpatentable over Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12), in view of Chilukuri et al. (Indian Journal of Psychological Medicine, 2014. Vol. 36, 1: 71-76) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claims 1, 4-5, 22, and 24 rejected under 35 U.S.C. 103 as being unpatentable over Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12), in view of Lehrer et al. (Discovery medicine, 2019. Vol. 28(154): 205–212) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claims 1, 5, 19-20, and 24 rejected under 35 U.S.C. 103 as being unpatentable over Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12), in view of Richard et al. (British Journal of Anaesthesia, 1994. Vol. 73(3): 432), and Ertzgaard et al. (Journal of rehabilitation medicine, 2017. 49(3), 193–203) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claims 1, 4-10, 19-20, and 24 rejected under 35 U.S.C. 103 as being unpatentable over Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12), in view of Caers et al. (US 2016/0074340 A1) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claims 1-2, 5-9, 18, and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 8, 11-12, 14-16 of copending Application No. 18/288,870 (reference application; referred to herein as ‘870 application), in view of Frank et al. (Psychiatry research, 1992. Vol. 43, 3: 231–241) are withdrawn in light of the claim amendment filed on May 14, 2025.
Claims 1-2, and 5-10 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 23, 25, 61 and 62 of copending Application No. 16/464,383 (reference application; referred to herein as ‘383 application) are withdrawn in light of the claim amendment filed on May 14, 2025.
Status of Claims
Claims 1-4, 6-13, 18-20 and 22-24 are pending. Claims 3, 11-13, and 23 remain withdrawn.
Claims 1-2, 4, 6-10, 18-20, 22 and 24 are under examination in accordance to the elected species along with the species set forth in the Expansion of Election of Species Requirement section above.
Priority
The instant application 17/431,468 filed on August 17, 2021 is a 371 of PCT/US2020/045005 filed on August 5, 2020, which claims priority to, and the benefits of U.S. Provisional Application No.
62/882,858 filed on August 5, 2019.
Response to Arguments
Applicant's arguments filed on May 14, 2025 with respect to the disclosure of the prior-filed application, U.S. Provisional Application No. 62/882,858, set forth in the previous Non-Final Office Action mailed on November 14, 2024 have been fully considered and they are persuasive; therefore, the claimed invention is entitled for the benefits of U.S. Provisional Application No. 62/882,858 filed on August 5, 2019.
Claim Interpretation
Regarding claim 2, “wherein the postpartum related symptom is selected from dysphoria, diminished interest or pleasure in activities, decrease or increase in appetite, troubled sleep or hypersomnia, insomnia, psychomotor agitation or retardation, fatigue or loss of energy, irritability, feelings of worthlessness or excessive or inappropriate guilt, diminished ability to think or concentrate or indecisiveness, inability to bond with an infant, anhedonia, anxiety, and depression” is reasonably construed by the Examiner to refer to selecting a single species of postpartum related symptom in the claim, in this case, the elected dysphoria is being selected.
Regarding claim 18, the recitation of “wherein the administration is by a route selected from…” is reasonably construed by the Examiner to refer to selecting a single species of administration route in the claim, in this case, the elected intramuscular route is being selected.
Regarding claim 20, the recitation of “wherein the muscle relaxant is selecting from” is reasonably construed by the Examiner to refer to selecting a single species of muscle relaxant in the claim, in this case, the elected baclofen is being selected.
Regarding claim 22, the recitation of “further comprising concurrently administering an anti-inflammatory agent selected from NSAIDs and corticosteroids” is reasonably construed by the Examiner to refer to selecting an anti-inflammatory agent that is a NSAID or corticosteroid, in this case, the elected NSAID is being selected.
Claim Objections
Claims 1-2 are objected to because of the following informalities (newly applied as necessitated by amendment):
Regarding claim 1, the phrase of “wherein following the administering” should read- wherein following the administration-, because the term “administering” is a present participle rather than a standalone noun; and the term -administration- is the proper noun form for the act of administering.
Regarding claim 2, the recitation of “inability to bond with an infant” in line 5 appears to be referring to the same “child” that consumes breast milk set forth in claim 1 (see line 6). Therefore, the term “an infant” recites in claim 2 should read –the child—for the sake of consistency.
Appropriate correction is required.
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.
Claims 2 and 24 are 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 (newly applied as necessitated by amendment). 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.
Regarding claim 2, the claim recites “wherein the postpartum related symptom is selected from dysphoria, diminished interest or pleasure in activities, decrease or increase in appetite, troubled sleep or hypersomnia, insomnia, psychomotor agitation or retardation, fatigue or loss of energy, irritability, feelings of worthlessness or excessive or inappropriate guilt, diminished ability to think or concentrate or indecisiveness, inability to bond with an infant, anhedonia, anxiety, and depression”. To the extent that the claim is drawn to treating all of these postpartum related symptoms together, then there is insufficient written basis for treating these postpartum related symptoms together.
In the present case, the specification discloses “
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” in page 3, line 23-33 of the specification; and further discloses “
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” in page 3, line 34 to page 3, line 6 of the specification. It is noted that the specification does not disclose the claimed invention is drawn to treating a specific combination of “dysphoria, diminished interest or pleasure in activities, decrease or increase in appetite, troubled sleep or hypersomnia, insomnia, psychomotor agitation or retardation, fatigue or loss of energy, irritability, feelings of worthlessness or excessive or inappropriate guilt, diminished ability to think or concentrate or indecisiveness, inability to bond with an infant, anhedonia, anxiety, and depression”.
Therefore, it is not apparent that applicant was actually in possession of, and intended to be used within the context of the present invention, to treating these postpartum related symptoms recites in claim 2 together.
Regarding claim 24, the claim recites “wherein the subject is diagnosed as suffering from Postpartum Mood and Anxiety Disorders (PMAD) and Postpartum Depression (PPD)”. There is insufficient written basis for the subject species instantly claimed.
In the present case, the specification only discloses “In certain embodiments of any of the above methods, the subject being treated is suffering from Postpartum Mood and Anxiety Disorders (PMAD), Postpartum Psychosis (PPP), Postpartum Depression (PPD), Anxiety (PPA), Post-Traumatic Stress (PPPTSD), obsessive compulsive disorder (PPOCD), or Postpartum Bipolar I and II disorders (PPBPD)”. It is noted that the specification does not discloses the subject is diagnosed as having a combination of postpartum mood and anxiety disorders and postpartum depression.
Therefore, it is not apparent that applicant was actually in possession of, and intended to be used within the context of the present invention, to incorporate the subject that is diagnosed as suffering from postpartum mood and anxiety disorders and postpartum depression.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 2 is 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 (newly reapplied as necessitated by amendment).
Regarding claim 2, the recitation of “
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” renders the claim indefinite, because the claim when interpret in light of specification appears to be selecting one postpartum related symptom from the list. In fact, the elected species actually indicates only one of these postpartum related symptom is being selected, in this case, “dysphoria”; However, when the term “and” is used before the last postpartum related symptom (“depression”) in the context of selection, the claim can also be interpreted as selecting all the postpartum related symptoms from the list. Therefore, it is not clear if applicant is intending to select one postpartum related symptom from the list, select more than one postpartum related symptoms from the list, or select all of these postpartum related symptoms together. If Applicant is intending to refer to selecting one postpartum related symptom from the list, Applicant can amend the claim to recites “wherein the postpartum related symptom is selecting from the group consisting of”.
In order to advance prosecution, the Examiner is examining the claim to the extent that the one of the postpartum related symptoms from the list is being selected.
Response to Arguments
Applicant's arguments filed on May 14, 2025 with respect to the rejection of claim 2 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 have been fully considered but they are not persuasive.
Applicant amends claim 2 by deleting the phrase of “psychomotor agitation or retardation” and “and in more severe states recurrent thoughts of death, suicidal ideation or suicidal attempts and anger and aggressive feelings and behavior potentially directed towards the newborn, or partners and parents and a variety of somatic symptoms that may also be present which may include varying degrees of fatigue, back pain, breast tenderness and discomfort, headaches and other manifestations as well as underlying emotional and physical problems that may be exacerbated including dysphoria, anxiety and Post Traumatic 5tress Disorder, but not limited to these”. Applicant further added the term “and” before the last postpartum related symptom (“depression”) in line 5. Each of these findings demonstrate that the amendment changes the scope of the claim and necessitated a modification of the rejection on the record.
Applicant argues the claim is amended to address the concerned raised by the Office. Since Applicant did not put forth any arguments against this rejection, the rejection of claim 2 is withdrawn in view of the claim amendment that changes the scope of the claim; However, upon further consideration, the rejection has been reapplied as necessitated by amendment for the reasons set forth herein.
New Claim Rejections - 35 USC § 103
Newly Applied as Necessitated by Amendment
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 1-2, 6, 10, 18 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Lombard (US 2018/0042936 A1), in view of Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12; cited under “Non-Patent Literature Documents”, cited no. M in the IDS filed on 9/13/2024) and Reset Ketamine (“Ketamine and Postpartum Depression” [Online]. Published on November 12, 2018) (newly applied as necessitated by amendment).
Lombard teaches a maintenance therapy for depression remission comprising: (a) administering to a patient who suffers from depression a therapeutically effective amount of ketamine for a first predetermined period of time of up to about 12 months; and (b) subsequent to the first predetermined period, administering to the patient in need of maintenance therapy, a therapeutically effective amount of tianeptine (see e.g., [0016]). Lombard further teaches the present disclosure provides a long-term treatment of depression, anxiety and/or other related diseases with tianeptine, subsequent to ketamine treatment (see e.g., [0042]). Lombard further teaches depression, anxiety and/or other related diseases to be treated by the present invention include, inter alia, postpartum depression, anxiety, mood disorder (see e.g., [0054]). Please note the depression of postpartum depression taught by Lombard is a postpartum related symptom. Lombard further teaches the ketamine treatment comprises administering to the patient a dose of about 0.1 mg/kg/day to about 3.0 mg/kg/day (see e.g., [0008]). Lombard further teaches ketamine is administered ranging from daily to weekly, daily to monthly, biweekly, or monthly depending on response (see e.g., [0066]). Lombard further teaches ketamine and tianeptine may be administered by one or more of a variety of routes, including, inter alia, intramuscular (see e.g., [0081]). Lombard further teaches chronic use of ketamine has been reported to be associated with neurotoxicity and/or toxicities to other organ; therefore, there is a need for ketamine responder to have a replacement and/or a maintenance therapy that avoids long term use of ketamine (see e.g., [0005]-[0006]). Lombard further teaches the tianeptine treatment is initiated up to, inter alia, about 12 months or about 2 weeks after the ketamine treatment (see e.g., [0043]).
Lombard does not teach the subject is breast feeding and wherein following the administering, the subject does not express breast milk for consumption by a child for a period of at least 6 hours in claim 1.
Xia et al. teaches chronic pre-pregnancy stress contributed to long-lasting postpartum depression and dysregulation in Akt-mTOR expression and ratio of GluR1/NR1 using an animal model, and specifically teaches mice experiencing both pre-pregnancy stress and parturition displayed depressive-like behavior at three weeks postpartum (referred to herein as postpartum depression-like mice) (see e.g., p. 2, “Chronic pre-pregnancy stress contributed to long-lasting PPD and dysregulation in Akt-mTOR expression and ratio of GluR1/NR1” section, line 5-7). Xia et al. further teaches at three weeks postpartum, said postpartum depression-like mice treated with a single dose of ketamine (30 mg/kg, i.p.) improved the performance in sucrose performance test, forced swim test, latency to eat, and food consumption in the novelty-suppressed feeding test compared to vehicle treated group (see e.g., p. 3, “A single dose of ketamine ameliorated behavioral deficits and normalized NR1/Akt/mTOR/GluR1 signaling in the PPD-like mice” section, first paragraph; see Figure 3. for ketamine dosing). Xia et al. further teaches acute ketamine reversed the changes in the postpartum depression-like mice in hippocampal expression of NR1, Akt-mTOR signaling proteins and GluR1 (see e.g., p. 3, “A single dose of ketamine ameliorated behavioral deficits and normalized NR1/Akt/mTOR/GluR1 signaling in the PPD-like mice” section, first paragraph).
Reset Ketamine teaches ketamine’s role in treating postpartum depression is extrapolated from the evidence behind treating treatment resistant depression (TRD). Reset Ketamine further teaches ketamine works by blocking N-Methyl-D-Aspartate (NMDA) receptor from activation by the glutamate neurotransmitter, reducing activity of the default mode network, and increasing brain-derived neurotrophic factor to promote neuroplasticity (see e.g., 5th paragraph). Reset Ketamine further teaches ketamine is frequently used during delivery of the baby; However, there are currently no studies looking at ketamine transfer to breast milk. Reset Ketamine recommend pumping for 2 days prior to the infusion and storing this milk, then for 2 days after the ketamine infusion, to “pump & dump” to clear ketamine and its metabolite from breast milk (see e.g., 2nd last paragraph before “references” section).
In the present case, Lombard clearly teaches a method of treating depression comprising administering about 0.1 mg/kg/day to about 3.0 mg/kg/day of ketamine to a patient who suffers from depression, including postpartum depression. The difference between the method of Lombard and the claimed method is that said prior art does not expressly teach the limitation of “the subject is breast feeding” and “wherein following the administering, the subject does not express breast milk for consumption by a child for a period of at least 6 hours”. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Lombard to selectively choose to treat postpartum depression as the depression, as taught by Xia et al., and then incorporate breast feeding subject that does not express breast milk for consumption by a child for 2 days as the patient. One would have been motivated to do so, because Xia et al. clearly teaches ketamine reduces depressive-like behavior in a mice model of postpartum depression; and Reset Ketamine teaches ketamine is useful for treating postpartum depression and recommend pumping breast milk for 2 days prior to the ketamine treatment and storing this milk, then for 2 days after the ketamine infusion, to pump and dump the breast milk in order to clear the metabolites of ketamine. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering about 0.1 mg/kg/day to about 3.0 mg/kg/day of ketamine to a breast feeding subject with postpartum depression will successfully treat the postpartum depression, and said subject should not express breast milk for consumption by a child for a period of 2 days to ensure the clearance of ketamine metabolites. Please note the depression symptom of postpartum depression will necessarily be treated by treating the postpartum depression, and said depression is a postpartum related symptom in claim 2. 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 claim 6, the claim recites the limitation of “wherein the ketamine… is administered once or more daily… depending on the presence and/or severity of postpartum related symptoms”. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Lombard, Xia et al. and Reset Ketamine set forth above to administer the ketamine once daily through routine optimization. One would have been motivated to do so, because Lombard teaches ketamine can be administered ranging from daily to weekly depending on response. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by changing the frequency of ketamine administration starting from once daily would have successfully optimize the treatment response.
Regarding claim 10, the claim recites the limitation of “wherein the method comprises administering an average daily dose of from 10 mg to 200 mg of racemic ketamine, or a pharmaceutically acceptable salt thereof, to the subject”, and said limitation is drawn to the average daily dose of ketamine. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). The claimed limitation would have been obvious by the fact that Lombard teaches ketamine is administered at a dose of about 0.1 mg/kg/day to about 3.0 mg/kg/day set forth in the method above. The average daily dose of ketamine can be calculated as follows:
For example, if a patient weights 70 kg, then the lower limit of daily dose can be calculated as follows:
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m
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/
d
a
y
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7
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g
of ketamine per day;
; and the upper limit of daily dose can be calculated as follow:
3
m
g
/
k
g
/
d
a
y
×
70
k
g
=
210
m
g
of ketamine per day;
, gives an average daily dosage of about 7 mg to 210 mg of ketamine. Therefore, about 0.1 mg/kg/day to about 3.0 mg/kg/day of ketamine set forth in the method above renders obvious the limitation instantly claimed.
Regarding claim 18, the claim recites the limitation of “wherein the administration is by a route selected from…intramuscular…”. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Lombard, Xia et al. and Reset Ketamine set forth above to administer the ketamine through intramuscular route. One would have been motivated to do so, because Lombard teaches ketamine can administered by one or more of a variety of routes, including intramuscular. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering the ketamine through intramuscular route would have successfully deliver said ketamine for the treatment of postpartum depression.
Regarding claim 24, the claim recites the limitation of “wherein the subject is diagnosed as suffering from Postpartum Mood and Anxiety Disorders (PMAD) and Postpartum Depression (PPD)”. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Lombard, Xia et al. and Reset Ketamine set forth above to incorporate the subject that has also been diagnosed as suffering from postpartum mood and anxiety disorder in addition to the postpartum depression. One would have been motivated to do so, because Lombard teaches the depression, anxiety and/or other related diseases that can be treated by ketamine and subsequent tianeptine include postpartum depression, anxiety and mood disorder. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the therapeutic effective amount of ketamine followed by tianeptine would successfully treat anxiety, mood disorder, and depression in the postpartum women; and that renders obvious the limitation instantly claimed.
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.
Claims 1-2, 6, 10, 18 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Lombard (US 2018/0042936 A1), in view of Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12; cited under “Non-Patent Literature Documents”, cited no. M in the IDS filed on 9/13/2024) and Reset Ketamine (“Ketamine and Postpartum Depression”[Online]. Published on November 12, 2018) as applied to claims 1-2, 6, 10, 18 and 24 above, and further in view of Frank et al. (Psychiatry research, 1992. Vol. 43, 3: 231–241; cited in the previous Non-Final Office Action mailed on November 14, 2024)(newly applied as necessitated by amendment).
To the extent that the postpartum related symptom is the elected dysphoria, then the following 35 U.S.C. 103 rejection applies.
The teachings of Lombard, Xia et al. and Reset Ketamine are set forth above and applied as before.
Lombard, Xia et al. and Reset Ketamine do not teach the elected postpartum related symptom (“dysphoria”) in claim 2.
Frank et al. teaches dysphoria is a core element of the syndrome of depression (see e.g., abstract; line 13-14). Frank et al. further teaches dysphoria represents symptoms of negative self-evaluation, depressed affect, and suicidal ideation (see e.g., abstract, line 11-12).
In the present case, the method of Lombard, Xia et al. and Reset Ketamine set forth above is silent about “dysphoria”, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Xia et al. and Reset Ketamine set forth above to further incorporate dysphoria. One of ordinary skill in the art would have been motivated to do so, because Frank et al. teaches dysphoria is a core syndrome of depression. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by treating postpartum depression with a dose of about 0.1 mg/kg/day to about 3.0 mg/kg/day of ketamine, one will also be treating dysphoria by treating the underlying cause of dysphoria (depression).
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.
Claims 1-2, 4, 6, 10, 18, 22 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Lombard (US 2018/0042936 A1), in view of Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12; cited under “Non-Patent Literature Documents”, cited no. M in the IDS filed on 9/13/2024) and Reset Ketamine (“Ketamine and Postpartum Depression”[Online]. Published on November 12, 2018) as applied to claims 1-2, 6, 10, 18 and 24 above, and further in view of Lehrer et al. (Discovery medicine, 2019. Vol. 28(154): 205–212; cited in the previous Non-Final Office Action mailed on November 14, 2024) (newly applied as necessitated by amendment).
The teachings of Lombard, Xia et al. and Reset Ketamine are set forth above and applied as before.
Lombard, Xia et al. and Reset Ketamine does not teach the postpartum related symptom is refractory to treatment recites in claim 4. Lombard, Xia et al. and Reset Ketamine also does not teach concurrently administering the NSAID as an anti-inflammatory agent in claim 22.
Lehrer et al. teaches nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in treating animal models of depression, alone or with antidepressant drugs, but results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported (see e.g., abstract). Lehrer et al. further teaches significantly less depression was reported in patients treated with naproxen (NSAID) or aspirin (NSAID) compared to acetaminophen (non-NSAID), but significantly more depression in patients treated with celecoxib (NSAID) compared to acetaminophen (non-NSAID) (see e.g., abstract). Lehrer et al. further teaches NSAIDs might be valuable agents for treating depression and suicide (see e.g., abstract).
With respect to claim 4, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Lombard, Xia et al. and Reset Ketamine set forth above to incorporate the depression that is refractory to treatment with NSAID celecoxib. One would have been motivated to do so, because Lehrer et al. teaches NSAIDs useful for treating animal models of depression alone can have mixed results in depression outcomes, for example, celecoxib (NSAID) treated patients has more depression reported. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the depression refectory to celecoxib (NSAID) would successfully be treated by the ketamine by switching the causative medication (celecoxib).
With respect to claim 22, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method Lombard, Xia et al. and Reset Ketamine set forth above to further incorporate the concurrent administration of naproxen (NSAID) or aspirin (NSAID), because each is taught by the prior art to be useful for the same purpose (treating depression). See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One would have been motivated to do so, because Lehrer et al. teaches nonsteroidal anti-inflammatory drugs is an effective in treating animal models of depression, alone or with antidepressant; and further teaches naproxen or aspirin has better depression outcomes. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering naproxen or aspirin concurrently with the method of Lombard, Xia et al. and Reset Ketamine would successfully treated depression, because each shown to be useful separately for the same purpose would be expected to be similarly useful when used together. With further respect to “concurrently administering…” in the said claim, 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 that by administering the ketamine with naproxen or aspirin of Lehrer et al. concurrently to the patient would treat depression.
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.
Claims 1-2, 6, 10, 18-20 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Lombard (US 2018/0042936 A1), in view of Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12; cited under “Non-Patent Literature Documents”, cited no. M in the IDS filed on 9/13/2024) and Reset Ketamine (“Ketamine and Postpartum Depression”[Online]. Published on November 12, 2018) as applied to claims 1-2, 6, 10, 18 and 24 above, and further in view Richard et al. (British Journal of Anaesthesia, 1994. Vol. 73(3): 432) and Ertzgaard et al. (Journal of rehabilitation medicine, 2017. 49(3), 193–203).
Please note Richard et al. and Ertzgaard et al. are each cited in the previous Non-Final Office Action mailed on November 14, 2024.
The teachings of Lombard, Xia et al. and Reset Ketamine are set forth above and applied as before.
Lombard, Xia et al. and Reset Ketamine does not teach concurrently administering to the subject the elected muscle relaxant (“baclofen”) in claims 19-20.
Richard et al. teaches ketamine increases general muscle tone and has been reported to cause myoclonic movements (muscle spasms) (see e.g., p. 432, right column, 2nd paragraph).
Ertzgaard et al. teaches results suggest that oral baclofen may be effective in many patients with spasticity, regardless of the underlying disease or severity, and that it is at least comparable with other antispasmodic agents (see e.g., abstract).
It would have been prima facie obvious to one of ordinary skill in the art that the time the application was filed to modify the method of Lombard, Xia et al. and Reset Ketamine set forth above to further incorporate concurrent administration of baclofen. One would have been motivated to do so, because Richard et al. teaches ketamine can cause muscle spasms, and Ertzgaard et al. teaches baclofen is effective in treating patient with spasticity. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering baclofen concurrently with the method of Lombard, Xia et al. and Reset Ketamine set forth above would successfully treated muscle spasms induced by the ketamine. With further respect to “concurrently administering…” in the said claim, 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 that by administering the ketamine and baclofen concurrently to the patient would treat muscle spasms cause by ketamine.
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.
Claims 1-2, 6-8, 10, 18 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Lombard (US 2018/0042936 A1), in view of Xia et al. (Sci Rep., 2016. Vol. 6, 35042: 1-12; cited under “Non-Patent Literature Documents”, cited no. M in the IDS filed on 9/13/2024) and Reset Ketamine (“Ketamine and Postpartum Depression”[Online]. Published on November 12, 2018) as applied to claims 1-2, 6, 10, 18 and 24 above, and further in view Caers et al. (US 2016/0074340 A1).
The teachings of Lombard, Xia et al. and Reset Ketamine are set forth above and applied as before.
Lombard, Xia et al. and Reset Ketamine does not teach the administration is once daily for a period of from 1 to 10 days, followed by a period of at least two weeks during which no ketamine is administered to the subject in claim 7. Lombard, Xia et al. and Reset Ketamine also does not teach the administration is once daily for a period of from 1 to 8 days, followed by a period of at least two weeks during which no ketamine is administered to the subject in claim 8.
Caers et al. teaches ketamine (a racemic mi