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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 55 – 57, and 71 – 73 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 55, the use of “e.g.,” in line 5 of the claim is the abbreviation of “exempli gratia” and means “for the sake of example;” thus, the abbreviation “e.g.,” is given the same meaning as the phrase “for example.” The phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase, that is injectable ketamine, are part of the claimed invention. See MPEP § 2173.05(d). Claim 56 is included in the rejection for depending on claim 55; thus, including the recitation of, “e.g.,” without correcting the indefinite issue.
Regarding claim 57, the claim recites the limitation "the required dose" in line 5. There is insufficient antecedent basis for this limitation in the claim because claim 54, from which claim 57 depends, does not recite the administration of “a required dose.”
Regarding claim 71, the phrase “including treatment resistant depression,” in line 1 of the claim is interpreted as having the same meaning as the phrase “such as.” The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase, that is “treatment resistant depression,” are part of the claimed invention. See MPEP § 2173.05(d). Claims 72 – 73 are included in the rejection for depending on claim 71; thus, including the recitation of, “including treatment resistant depression,” without correcting the indefinite issue.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 54 – 55, and 61 – 66 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arabzadeh et. al. ((2018), Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 235, 236 – 241; cited on the IDS dated January 10th, 2024) as evidenced by MacQueen et.al.((2001), The Selective Serotonin Reuptake Inhibitor Sertraline: Its Profile and Use in Psychiatric Disorders, CNS Drug Review, 7, 1 – 24).
Regarding claims 54 – 55, and 61 – 66, Arabzadeh et. al. teach that depression (claim 54) is a common disease with a lifetime prevalence of 20–30% worldwide and a huge burden on the healthcare system (page 236 column 1 paragraph 1). Additionally, Arabzadeh et. al. teach that the slow response along with frequent side effects sometimes cause nonadherence and increase risk of suicide (claim 62)(page 236 column 1 paragraph 1). Thus, Arabzadeh et. al. teach that there seems to be a need for faster and more effective treatments (page 236 column 1 paragraph 1). Furthermore, Arabzadeh et. al. teach that ketamine is an NMDA receptor antagonist and was recently found to exhibit a rapid-onset treatment effect on major depressive disorder (MDD) (claim 65) (page 236 column 2 paragraph 1). Moreover, Arabzadeh et. al. teach that the rapid onset effect was even present in patients with treatment resistant depression (claim 66) (TRD) (page 236 column 2 paragraph 1).
Arabzadeh et. al. teach that in a randomized, placebo-controlled double-blind trial was conducted over 6 weeks (page 237 column 1 paragraph 4), patients received sertraline (claim 55) (150 mg a day) in combination with either 50 mg/day ketamine (claim 64) or placebo (claims 54 and 61) (page 237 column 1 paragraph 6). Furthermore, Arabzadeh et. al. teach that different doses of oral ketamine (claim 54) have been used in previous studies ranging from a fixed dose 0.5 mg/kg or 150 mg/day (page 237 column 1 paragraph 6), to the titrated drug range of from 0.5 mg/kg to 0.7mg/kg or 25–300 mg/day (page 237 column 1 paragraph 6 and column 2 paragraph 1). Moreover, Arabzadeh et. al. teach that the frequency of administration also varies from once daily usage to three times a day (page 237 column 2 paragraph 1). Additionally, Arabzadeh et. al. teach that ketamine prescription started with initial dose (claims 61 and 63) of sertraline and was prescribed at 25 mg twice daily (page 237 column 2 paragraph 1).
Regarding claim 55, limitation that, “the second anti-depressant agent is selected from the group consisting of selective serotonin reuptake inhibitors (SSRIs),” as evidenced by MacQueen et. al. sertraline, is an antidepressant and antipanic agent that is a potent and selective inhibitor of serotonin reuptake into the presynaptic terminal (page 2 paragraph 1). Thus the prior art teaching of Arabzadeh et. al. to the administration of sertraline (150 mg a day) in combination with either 50 mg/day ketamine or placebo (page 237 column 1 paragraph 6) anticipates the method of claim 55.
Thus the prior art teaching of Arabzadeh et. al. anticipates the method of treating a depressive disorder in a subject comprising administering an active pharmaceutical agent to a subject in need thereof wherein the active pharmaceutical agent is administered orally, in combination with a second anti-depressant agent; and wherein the active pharmaceutical agent is ketamine as recited in instant claim 54. Therefore, the prior art teachings of Arabzadeh et. al. anticipates instant claims 54 – 55, and 61 – 66.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 57 is rejected under 35 U.S.C. 103 as being unpatentable over Arabzadeh et. al. ((2018), Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 235, 236 – 241; cited on the IDS dated January 10th, 2024) as applied to claims 54 – 55, and 61 – 66, above.
The teaching of Arabzadeh et. al. as it relates to claim 54, from which claim 57 depends, is given previously in this office action and are fully incorporated here.
However, Arabzadeh et. al. fails to exemplify the administration of the active pharmaceutical agent, that is ketamine, (ii) at a dose of 120 – 240 mg per day (claim 57).
Nevertheless, as mentioned above, Arabzadeh et. al. teach that different doses of oral ketamine have been used in previous studies ranging from a fixed dose 0.5 mg/kg or 150 mg/day (page 237 column 1 paragraph 6), to the titrated drug range of from 0.5 mg/kg to 0.7mg/kg or 25–300 mg/day (page 237 column 1 paragraph 6 and column 2 paragraph 1). Moreover, Arabzadeh et. al. teach that the frequency of administration also varies from once daily usage to three times a day (page 237 column 2 paragraph 1). While the instant claim 57 recites the administration of the active pharmaceutical agent, that is ketamine, at a dose of 120 – 240 mg per day; the instant dosage range overlaps with the prior art range of from 0.5 mg/kg to 0.7mg/kg or 25–300 mg/day. 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). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)(MPEP 2144.05(I)).
Claims 56 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Arabzadeh et. al. ((2018), Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 235, 236 – 241; cited on the IDS dated January 10th, 2024) as applied to claims 54 – 55, and 61 – 66 above, further in view of Patent Application Publication US 2013/0236573 A1 to Singh et. al. (herein after Singh’573).
The teaching of Arabzadeh et. al. as it relates to claims 54, from which claims 56 and 58 depend, is given previously in this office action and are fully incorporated here.
However, Arabzadeh et. al. fails to teach a method wherein the second anti-depressant agent is administered subcutaneously, intravenously, or intramuscularly (claim 56). Moreover, Arabzadeh et. al. fails to teach a method wherein the second anti-depressant agent is administered subcutaneously: (i) at a dose of 0. 5-1. 0 mg/kg; and/ or (ii) for 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7, weeks, 8 weeks, 9 weeks, 10 weeks, 15 weeks, 20 weeks, 25 weeks, 30 weeks, 35 weeks or 40 weeks (claim 58).
Nevertheless, Singh’573 teach a method for the treatment of treatment -refractory or treatment resistant depression comprising administering to a patient in need thereof a therapeutically effective amount of esketamine and at least one antidepressant (page 2 paragraph 0014). Furthermore, Singh’573 teach that esketamine is another name for the S-ketamine enantiomer (page 1 paragraph 0006). Moreover, Singh’573 teach that pharmaceutical compositions for the treatment of treatment-refractory or treatment-resistant depression (TRD) containing esketamine, optionally in combination with one or more antidepressants, with a pharmaceutically acceptable carrier (page 5 paragraph 0055).
Additionally, Singh’573 teach that where the esketamine and the antidepressant(s) are administered in separate dosage forms, the number of dosages administered per day for each compound may be the same or different and that esketamine and the antidepressant(s) may be administered via the same or different routes of administration (page 4 paragraph 0048). Singh’573 teach that suitable methods for administration include oral, intravenous (iv), intranasal (in) intramuscular (im), subcutaneous ( sc ) (claim 56), transdermal, and rectal (page 5 paragraph 0048). Furthermore, Singh’573 teach that the optimal dosages to be administered may be readily determined by those skilled in the art, and will vary with the particular compound or compounds used, the mode of administration, the strength of the preparation and the advancement of the disease condition (page 5 paragraph 0049).
Additionally, Singh’573 teach that the pharmaceutical compositions herein will contain, per unit dosage unit, e.g., tablet, capsule, powder, injection, suppository, teaspoonful, and the like, of from about 0.01 mg to about 1000 mg or any amount or range therein, and may be given at a dosage of from about 0.01 mg/kg to about 1.5 mg/kg (claim 58) (page 5 paragraph 0056). While instant claim 58 recites the administration of the active pharmaceutical agent, that is ketamine, at a dose of 0.5 – 1.0 mg per day; the instant dosage range overlaps with the prior art range of from 0.01 mg/kg to 1.5 mg/kg. 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). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)(MPEP 2144.05(I)).
Therefore, it would have been obvious before the effective filing date of the instant application to modify the method of Arabzadeh et. al. that for the administration of the second anti-depressant in view of Singh’573, that is to administered the second anti-depressant subcutaneously. One of ordinary skill in the art would have been motivated to make this modification as an alternative dosage form. One of ordinary skill in the art would have had a reasonable expectation of success because may be readily determined by those skilled in the art, and will vary with the particular compound or compounds used, the mode of administration, the strength of the preparation and the advancement of the disease condition.
Claims 59 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Arabzadeh et. al. ((2018), Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 235, 236 – 241; cited on the IDS dated January 10th, 2024) as applied to claims 54 – 55, and 61 – 66 above, further in view of Patent Application Publication US 2013/0236573 A1 to Singh et. al. (herein after Singh’573).
The teaching of Arabzadeh et. al. as it relates to claims 54, from which claims 59 – 60 depend, is given previously in this office action and are fully incorporated here.
However, Arabzadeh et. al. fails to teach a method wherein the active pharmaceutical agent is comprised within a composition comprising one or more excipients selected from the group consisting of diluents and lubricants (claim 59). Moreover, Arabzadeh et. al. fails to teach a method wherein the composition comprises lactose monohydrate, magnesium stearate, and/or microcrystalline cellulose (claim 60).
Nevertheless, Singh’573 teach a method for the treatment of treatment -refractory or treatment resistant depression comprising administering to a patient in need thereof a therapeutically effective amount of esketamine and at least one antidepressant (page 2 paragraph 0014). Furthermore, Singh’573 teach that esketamine is another name for the S-ketamine enantiomer (page 1 paragraph 0006). Moreover, Singh’573 teach that pharmaceutical compositions for the treatment of treatment-refractory or treatment-resistant depression (TRD) containing esketamine, optionally in combination with one or more antidepressants, with a pharmaceutically acceptable carrier (page 5 paragraph 0055).
Additionally, Singh’573 teach that pharmaceutical compositions containing one or more of the compounds of the invention described herein as the active ingredient can be prepared by intimately mixing the compound or compounds with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques (page 6 paragraph 0055) and that the carrier may take a wide variety of forms depending upon the desired route of administration (e.g., oral, parenteral) (page 6 paragraph 0055). Singh’573 teach that for solid oral preparations such as, for example, powders, capsules, caplets, gelcaps and tablets, suitable carriers and additives include starches, sugars, diluents (claim 59), granulating agents, lubricants (claim 59), binders, disintegrating agents and the like (page 5 paragraph 0056). More specifically, Singh’573 teach that suitable binds for or oral administration in the form of a tablet or capsule, include magnesium stearate (claim 60) (page 6 paragraph 0061). Furthermore, Singh’573 teach that suitable pharmaceutically acceptable carriers are well known in the art (page 6 paragraph 0063).
Therefore, it would have been obvious before the effective filing date of the instant application to modify the method of Arabzadeh et. al. that is the oral administration of ketamine in view of Singh’573 that is to formulate the ketamine as an oral dosage form comprising magnesium stearate. One of ordinary skill in the art would have been motivated to make this modification as an alternative oral dosage form. One of ordinary skill in the art would have had a reasonable expectation of success because the methods for formulating active agents with pharmaceutically acceptable diluents and/or lubricants is well established in the art.
Claims 67 – 69, 71, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Arabzadeh et. al. ((2018), Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 235, 236 – 241; cited on the IDS dated January 10th, 2024) in view of Patent Application Publication US 2013/0236573 A1 to Singh et. al. (herein after Singh’573).
Regarding claims 67 – 69, 71, and 73, Arabzadeh et. al. teach that depression (claim 71) is a common disease with a lifetime prevalence of 20–30% worldwide and a huge burden on the healthcare system (page 236 column 1 paragraph 1). Additionally, Arabzadeh et. al. teach that the slow response along with frequent side effects sometimes cause nonadherence and increase risk of suicide (claim 62)(page 236 column 1 paragraph 1). Thus, Arabzadeh et. al. teach that there seems to be a need for faster and more effective treatments (page 236 column 1 paragraph 1). Furthermore, Arabzadeh et. al. teach that ketamine is an NMDA receptor antagonist and was recently found to exhibit a rapid-onset treatment effect on major depressive disorder (MDD) (claim 67) (page 236 column 2 paragraph 1). Moreover, Arabzadeh et. al. teach that the rapid onset effect was even present in patients with treatment resistant depression (claim 67) (TRD) (page 236 column 2 paragraph 1).
Arabzadeh et. al. teach that in a randomized, placebo-controlled double-blind trial was conducted over 6 weeks (page 237 column 1 paragraph 4), patients received sertraline (150 mg a day) in combination with either 50 mg/day ketamine (claim 67 and 71) or placebo (page 237 column 1 paragraph 6). Furthermore, Arabzadeh et. al. teach that different doses of oral ketamine (claim 67 and 71) have been used in previous studies ranging from a fixed dose 0.5 mg/kg or 150 mg/day (claims 69 and 73) (page 237 column 1 paragraph 6), to the titrated drug range of from 0.5 mg/kg to 0.7mg/kg or 25–300 mg/day (page 237 column 1 paragraph 6 and column 2 paragraph 1). Moreover, Arabzadeh et. al. teach that the frequency of administration also varies from once daily usage to three times a day (page 237 column 2 paragraph 1). Additionally, Arabzadeh et. al. teach that ketamine prescription started with initial dose of sertraline and was prescribed at 25 mg twice daily (page 237 column 2 paragraph 1).
However, Arabzadeh et. al. fails to teach a method comprising a subcutaneous or intravenous second anti-depressant agent wherein the second anti-depressant is an enantiomer of ketamine (claims 67 and 71). Moreover, Arabzadeh et. al. fails to teach a method wherein the second anti-depressant agent is administered at a dose of 0. 5-1. 0 mg/kg (claim 73) once a week for three to four weeks (claim 68).
Nevertheless, Singh’573 teach a method for the treatment of treatment -refractory or treatment resistant depression comprising administering to a patient in need thereof a therapeutically effective amount of esketamine and at least one antidepressant (page 2 paragraph 0014). Furthermore, Singh’573 teach that esketamine is another name for the S-ketamine enantiomer (page 1 paragraph 0006). Moreover, Singh’573 teach that pharmaceutical compositions for the treatment of treatment-refractory or treatment-resistant depression (TRD) containing esketamine, optionally in combination with one or more antidepressants, with a pharmaceutically acceptable carrier (page 5 paragraph 0055).
Additionally, Singh’573 teach that where the esketamine and the antidepressant(s) are administered in separate dosage forms, the number of dosages administered per day for each compound may be the same or different and that esketamine and the antidepressant(s) may be administered via the same or different routes of administration (page 4 paragraph 0048). Singh’573 teach that suitable methods for administration include oral, intravenous (iv), intranasal (in) intramuscular (im), subcutaneous (sc) (claims 67 and 71), transdermal, and rectal (page 5 paragraph 0048). Furthermore, Singh’573 teach that the optimal dosages to be administered may be readily determined by those skilled in the art, and will vary with the particular compound or compounds used, the mode of administration, the strength of the preparation and the advancement of the disease condition (page 5 paragraph 0049).
Additionally, Singh’573 teach that the pharmaceutical compositions herein will contain, per unit dosage unit, e.g., tablet, capsule, powder, injection, suppository, teaspoonful, and the like, of from about 0.01 mg to about 1000 mg or any amount or range therein, and may be given at a dosage of from about 0.01 mg/kg to about 1.5 mg/kg (claims 68 and 73) (page 5 paragraph 0056). Moreover, Singh’573 teach that the dosages, however, may be varied depending upon the requirement of the patients, the severity of the condition being treated and the compound being employed (page 5 paragraph 0056). Also, Singh’573 teach that the use of either daily administration or post-periodic dosing may be employed (page 5 paragraph 0056).
While instant claims 68 and 73 recite the administration of the active pharmaceutical agent, that is ketamine, at a dose of 0.5 – 1.0 mg per day; the instant dosage range overlaps with the prior art range of from 0.01 mg/kg to 1.5 mg/kg. 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). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)(MPEP 2144.05(I)). In regards to claim 68, recitation for a method wherein once a week for three to four weeks (claim 68). While the prior art is silent about the 3 to 4 week duration, Signh’573 teach that the dosages, however, may be varied depending upon the requirement of the patients, the severity of the condition being treated and the compound being employed (page 5 paragraph 0056). Thus Signh’573 suggest that the dosage regimen is highly optimizable and within the purview of one of ordinary skill in the art to determine.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the method of Arabzadeh et. al. that for the administration of the active pharmaceutical ketamine in combination with the second anti-depressant in view of Singh’573, that is to administered the second anti-depressant, that is esketamine subcutaneously. One of ordinary skill in the art would have been motivated to make this modification since both ketamine and esketamine have been shown to be useful in the treatment of treatment resistant depression. One of ordinary skill in the art would have had a reasonable expectation of success because as taught above both ketamine and esketamine are known to treat treatment resistant depression and both compounds can be formulated for administration as an oral tablet or as an injectable. Moreover as taught above the formulation and combination can be readily determined by those skilled in the art, and will vary with the particular compound or compounds used, the mode of administration, the strength of the preparation and the advancement of the disease condition.
Claims 70, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Arabzadeh et. al. ((2018), Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial, Journal of Affective Disorders, 235, 236 – 241; cited on the IDS dated January 10th, 2024) and Patent Application Publication US 2013/0236573 A1 to Singh et. al. (herein after Singh’573) as applied to claims 67 – 69, 71, and 73 above, further in view of European Patent Application EP 3501542 A1 to Canuso et. al. (herein after Canuso’542).
The teachings of Arabzadeh et. al. and Singh’573 as it relates to claims 67 and 70, from which claims 70, and 72 depend, is given previously in this office action and are fully incorporated here.
However, the prior art of Arabzadeh et. al. and Singh’573 fail to teach a method wherein the active pharmaceutical agent is administered at a dose of 120 – 240 mg per day, once a week for between 1 and 8 weeks and then twice a week thereafter (claim 70) nor a method comprising: first bringing the depressive disorder into remission using the oral dose of the active pharmaceutical agent combined with the subcutaneous or intravenous dose of the second antidepressant agent; and then maintaining the depressive disorder in remission by administering a further oral dose of the active pharmaceutical agent to the subject (claim 72).
Nevertheless, Canuso’542 teach methods for the treatment of depression which includes major depressive disorder and treatment resistant depression (page 8 paragraph 0026). Moreover, Canuso’542 teach methods of maintaining stable remission (claim 72) or stable response following the administration of a therapeutically effective amount of esketamine during an initial administration phase followed by at least five months of a subsequent administration phase (claim 72) (page 8 paragraph 0028). Canuso’542 teach that one skilled in the art will recognize that the maintenance phase described herein may continue until further treatment is not required and as indicated by, for example, prolonged remission of the depression (including for example, the remission of one or more symptoms associated with depression), social and/or occupational functional improvement to normal or premorbid levels, or other known measures of depression (page 15 paragraph 0084). Moreover, Canuso’542 teach that the antidepressant would be dosed as labeled for the treatment of major depressive disorder (MDD), in a manner appropriate for the patient's condition/health (page 16 paragraph 0089).
Additionally, Canuso’542 teach that the disclosed methods include administering esketamine
in one or two phases, i.e., an initial induction phase, and optionally in certain circumstances a maintenance phase (page 16 paragraph 0088). Furthermore, Canuso’542 teach that the induction phase should be about 4 to about 8 weeks, about 4 to about 7 weeks, about 4 to about 6 weeks, most preferably about 4 weeks (page 16 paragraph 0088). Canuso’542 also teach an embodiment wherein the patient has not responded to at least two oral antidepressants in the current depressive episode, the patient may be administered esketamine at least twice weekly solely with esketamine or along with a first oral antidepressant that is the same or different than the previously ineffective oral antidepressant in a first induction phase (page 16 paragraph 0091).
While the prior art of Canuso’542 fails to explicitly teach the administration of a dose of 120-240 mg per day once a week for 1 and 8 weeks and then twice a week thereafter (claim 70); the prior art does teach the administration of the esketamine in a series of phases that are dependent on the induvial patients’ response. Moreover, as taught above, Canuso’542 teach that the antidepressant would be dosed as labeled for the treatment of major depressive disorder (MDD), in a manner appropriate for the patient's condition/health (page 16 paragraph 0089). Thus Canuso’542 suggest that the dosage amount and frequency/duration are highly optimizable and patient dependent. Hence as established by the prior art of Arabzadeh et. al., Singh’573, and Canuso’542 it would have been within the purview of one of ordinary skill in the art to use the information taught, to optimize for the appropriate dosage regime and frequency.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the method of Arabzadeh et. al. and Signh’573 for the administration of the active pharmaceutical ketamine in combination with the second anti-depressant is esketamine in view of Canuso’542 that is wherein the active pharmaceutical agent is administered at a dose of 120 – 240 mg per day, once a week for between 1 and 8 weeks and then twice a week thereafter maintaining the depressive disorder in remission. One of ordinary skill in the art would have been motivated to make this modification to improve and maintain the mental health of the subject until complete remission. One of ordinary skill in the art would have had a reasonable expectation of success because the prior art teach that the dosage range and frequency are highly optimizable and within the purview of one of ordinary skill in the art.
Conclusion
Claims 54 – 73 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627