DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-9,14-15,22-26 and 34-36 are pending.
Claims 1-9,14-15,22-26 and 34-36 are rejected.
Priority
Acknowledgment is made that Instant Application 18/841,749, filed on 2024, Aug. 27, is a National Stage entry of PCT/EP2023/055052, filed on 2023, Feb. 28, which claims priority from Provisional Application 634,84,905, filed on 2023, Feb. 14 and Provisional Application 63,314,753, filed on 2022, Feb. 28.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 2025, Aug 28 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
Claim Interpretations
Claim 1 recites a “method of treating a subject manifesting at least one or more behaviors selected from the group consisting of”, which can have multiple interpretations. In one interpretation, points (a) – (f) are “the group” from which at least one or more behaviors are selected. In another interpretation, one or more behavior is selected from each of the groups (a) – (f). Both interpretations are discussed herein.
Claim Rejections - 35 USC § 102/35 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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
In the event that Applicant intends for claim 1 to be directed to points (a) – (f) are “the group” from which at least one or more behaviors are selected: Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Iyer (WO 2008/074703 A1; published 2008, Jun. 26) and/or are rejected under 35 U.S.C. 103 as being unpatentable over Iyer.
Claim 1 is directed to a method of treating a subject manifesting at least one or more behaviors associated with atypical depression, in which the subject is administered a composition comprising Compound 1, or a pharmaceutically acceptable salt thereof, wherein compound 1 is (3,4-dichloro-phenyl)-((S)-3-propyl-pyrrolidin-3-yl)-methanone (Table 1, left)
Iyer teaches hetero pyrrolidinyl ketone derivatives or pharmaceutically acceptable salts thereof, and further teaches pharmaceutical compositions, methods of using, and methods of preparing the compounds (title, abstract). Of the pyrrolidinyl ketone derivatives taught, Iyer specifically teaches (3,4-dichloro-phenyl)-((S)-3-propyl-pyrrolidin-3-yl)-methanone as compound 107 (Table 1, right), (Table 1, page 57).
Table 1. Instant compound 1 and compound 107 disclosed by Iver
Instant Compound 1
Iver Compound 107
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95
120
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Iyer does not explicitly teach an embodiment in which compound 107 or its analogues are administered to a subject for the amelioration of an adverse behavior associated with atypical depression, however, Iyer teaches the use of compound 107 and other pyrrolidinyl ketone derivatives for the treatment of diseases or conditions associated with serotonin, norepinephrine and/or dopamine neurotransmission (page 12, lines 20-25). The disclosed diseases include eating disorders, such bulimia and “binge-eating” (page 12, line 25), which reads on group (c) (ii) of instant claim 1: binge-eating and inappropriate compensatory behaviors. As such, a person of ordinary skill in the art would at once envisage the use of compound 107 as a therapeutic for behaviors associated with atypical depression.
In the alternative, Iyer teaches the eating disorders such as bulimia and “binge-eating” are disease states associated with serotonin, norepinephrine, and/or dopamine neurotransmission (page 12, lines 20-25). Iyer further teaches the efficacy of pyrrolidinyl ketone derivatives as human serotonin transporter antagonists (pages 164-166, Example 23), human norepinephrine transporter antagonists (pages 166-167, Example 24), and human dopamine transporter antagonists (pages 167-169, Example 25). Therefore, by applying prong (E) rationale of In re KSR Int’l Co., 550 U.S. 398 (2007), one of ordinary skill in the art would have found it prima facie obvious to select compound 107 from the finite list of compounds provided for use as a medicament for bulimia and “binge-eating” from the finite list of disease states associated with serotonin, norepinephrine, and/or dopamine neurotransmission in a predictable manner because analogues of compound 107 were shown to act as triple reuptake inhibitors.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
In the event that Applicant intends for claim 1 to be directed to one or more behaviors that are selected from the combination of each of the groups (a) – (f): Claim(s) 1-9, 14-15, 22-26 and 34-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Iyer (WO 2008/074703 A1; published 2008, Jun. 26) in view of Rao (WO 2004/009069 A1; published 2004, Jan. 29) as evidenced by Łojko (Atypical depression: current perspectives. Neuropsychiatr. Dis. Treat., 2017, 13, 2447-2456), and in view of Drejer (WO 2013/160273 A1; published 2013, Oct. 31).
Claim 1 is directed to a method of treating a subject manifesting at least one or more behaviors associated with atypical depression, in which the subject is administered a composition comprising Compound 1, or a pharmaceutically acceptable salt thereof, wherein compound 1 is (3,4-dichloro-phenyl)-((S)-3-propyl-pyrrolidin-3-yl)-methanone (Table 1, left)
Iyer teaches hetero pyrrolidinyl ketone derivatives or pharmaceutically acceptable salts thereof, and further teaches pharmaceutical compositions, methods of using, and methods of preparing the compounds (title, abstract). Of the pyrrolidinyl ketone derivatives taught, Iyer specifically teaches (3,4-dichloro-phenyl)-((S)-3-propyl-pyrrolidin-3-yl)-methanone as compound 107 (Table 1, above), (Table 1, page 57).
Iyer further teaches the use of compound 107, inter alia, for the treatment of diseases or conditions associated with serotonin, norepinephrine, and/or dopamine neurotransmission including binge-eating and inappropriate compensatory behaviors (instant group (c) (ii)) in the form of bulimia and “binge-eating” (page 12, line 25).
The difference between Iyer and the instant application is that Iyer fails to teach the use of hetero pyrrolidinyl ketone derivatives to ameliorate behaviors of instant groups (a) – (b), or (d) – (f).
However, Rao teaches methods for the prevention or treatment of atypical depression secondary to pain, wherein a therapeutically effective amount of a non-tricyclic triple reuptake inhibitor is administered to a subject (title, abstract). Rao further teaches the symptoms of atypical depression that can be treated comprises mood reactivity (instant group (a) (i)) (claim 14); and increased appetite (instant group (e) (i)) (page 9, lines 29-32).
One of ordinary skill in the art would be motivated to apply the teachings of Rao with the teachings Iver because Rao teaches the use of non-tricyclic triple reuptake inhibitors as a method of treating atypical depression. Iver teaches compound 107 is used in the treatment of depression, which includes major depression. Prior to the effective filing date of the current invention, it was known in the art that atypical depression is a subset of major depression (see Łojko, page 2, left column, paragraph 3). Additionally, Iver teaches that the disclosed hetero pyrrolidinyl ketone derivatives are triple reuptake inhibitors (page 4, lines 17-20). Based on the structure, compound 107 could additionally be classified as a non-tricyclic triple reuptake inhibitor and thereby is encompassed by the teachings of Rao. Accordingly, one of ordinary skill in the art would have found it prima facie obvious to use compound 107 of Iver for the treatment of atypical depression symptoms, such as mood reactivity and increased appetite.
The difference between the combined teachings above and the instant application is that the combined teachings fail to address the use of triple reuptake inhibitors in use of treating the behaviors of instant groups (b), (d), or (f).
However, Drejer teaches a method of using Tesofensine (
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) for reducing body weight or hyperphagia in Prader-Willi patients comprising administering Tesofensine or a pharmaceutically acceptable salt thereof, and further teaches pharmaceutical compositions (title, abstract). Drejer teaches that Tesofensine can be used as a medicament for the treatment of binge eating not associated with regular use of inappropriate compensatory behaviors (instant group (b) (i)), in the form of binge eating disorder (page 41, lines 25-26); a sense of lack of control over-eating (instant group (d) (iii)) in the form of compulsive over-eating (page 41, line 5); and restriction of energy intake relative to requirements leading to a significant low body weight (instant group (f) (i)) in the form of anorexia nervosa (page 49, lines 12-15).
One would be motivated to combine the teachings of Drejer with the combined teachings of Iyer and Rao because Drejer teaches that Tesofensine is triple reuptake inhibitor that was used in human subjects with a diagnosis of major depressive disorder (page 49, lines 9-14). Iver also teaches that the disclosed hetero pyrrolidinyl ketone derivatives are triple reuptake inhibitors used to treat major depression. Therefore, a person of ordinary skill in the art would have had a reasonable expectation of success that the compounds taught by Iver would also be an effective therapeutic option for binge eating disorder, compulsive over-eating, and anorexia nervosa.
Claims 2-7 are directed to a composition of Compound 1, wherein the composition is a pharmaceutical composition in a sustained release form as a unit dose from about 1 mg/kg to about 70 mg/kg that is administered orally once daily.
Iyer teaches compositions of compound 107 wherein the composition may be placed into pharmaceutical compositions (page 103, lines 33-34) in a sustained release form (page 104, lines 2-3), as a unit dose (page 103, lines 33-34). Iyer further teaches the compounds to be administered in a therapeutically effective amount, depending on numerous factors (e.g., severity of the disease), but typically in the range of 1-500 mg, or 1-100 mg, or 1-30 mg daily (page 103, lines 12-20), wherein the preferred manner of administration is oral using a convenient daily dosage regimen which can be adjusted according to the degree of affliction (page 103, lines 28-30). While Iyer does not explicitly teach dosage from about 1 mg/kg to about 70 mg/kg, one of ordinary skill in the art could reasonably arrive at the claimed concentration through routine optimization given the disclosed ranges, the weight of the subject, and the severity of the disease.
Claim 8 is directed to the method above wherein said subject manifests mood reactivity and at least two additional behaviors selected from the group consisting of increased appetite, hyperphagia, increased sleep, hypersomnia, leaden paralysis, and long-standing pattern of interpersonal rejection sensitivity resulting in significant social or occupational impairment.
The combined teachings of Iver, Rao, and Drejer are discussed above and incorporated herein by reference.
Rao further teaches non-tricyclic triple reuptake inhibitors are used in treating symptoms of atypical depression including by mood reactivity (claim 14), hypersomnia, increased appetite or weight gain, leaden paralysis, or a long-standing pattern of extreme sensitivity to perceived interpersonal rejection (page 9, lines 29-32).
Claim 9 is directed to the method of claim 8 wherein the subject does not meet the criteria for melancholic depression or catatonia.
The combined teachings of Iver, Rao, and Drejer are discussed above and incorporated herein by reference.
By the time of the effective filing date of the current invention, it was known in the art that the definition of atypical depression includes that the patient cannot meet the criteria for melancholic or catatonic depression (see Łojko, page 2, left column, paragraph 3). Accordingly, because Rao teaches the use of triple reuptake inhibitors as a therapeutic option for atypical depression, the disclosed patient population must necessarily not meet the criteria for melancholic depression or catatonia.
Claim 14 is directed to the method of claim 1 wherein the subject has been diagnosed with atypical depression.
The combined teachings of Iver, Rao, and Drejer are discussed above and incorporated herein by reference, whereby Rao teaches the treatment of subjects with atypical depression.
Claim 15 is directed to the method of claim 1 wherein the subject has been diagnosed with one or more behaviors selected from the group consisting of mood reactivity, increased appetite, hyperphagia, increased sleep, hypersomnia, leaden paralysis, and long-standing pattern of interpersonal rejection sensitivity resulting in significant social or occupational impairment.
The combined teachings of Iver, Rao, and Drejer are discussed above and incorporated herein by reference, whereby Rao teaches treatment of subjects afflicted with symptoms of atypical depression, including mood reactivity (claim 14), hypersomnia, increased appetite or weight gain, leaden paralysis, or a long-standing pattern of extreme sensitivity to perceived interpersonal rejection (page 9, lines 29-32).
Claims 22-23 are directed to the method of claim 1 wherein the subject has been diagnosed with and treated for depression.
Iyer teaches the use of compound 107 and other hetero pyrrolidinyl ketone triple reuptake inhibitors for the treatment of disease states in subjects associated with serotonin, norepinephrine, and/or dopamine (page 12, lines 13-30), wherein the disease state includes depression (page 13, lines 1-5).
Claims 24-25 are directed to the method of claim 1 wherein the method comprises treating a subject who has been diagnosed with depression and also manifests one or more atypical depression symptoms, wherein the atypical depression symptom is selected from the group consisting of mood reactivity, increased appetite, hyperphagia, increased sleep, hypersomnia, leaden paralysis, and long-standing pattern of interpersonal rejection sensitivity resulting in significant social or occupational impairment.
The teachings of Iyer, Rao, and Drejer are discussed above and incorporated herein by reference.
Iyer further teaches the use of triple reuptake inhibitors for the treatment of somatic symptoms such as eating disturbances (page 13, lines 1-5). The difference between this teaching and the instant application is that Iyer fails to teach exactly what kind of eating disturbances can be treated.
However, Drejer teaches that triple reuptake inhibitors can be used to treat hyperphagia, and increased appetite (page 41, lines 1-7). As discussed above, one would be motivated to use the compounds of Iyer to treat the conditions disclosed by Drejer because both sets of compounds are triple reuptake inhibitors. Therefore, one of ordinary skill in the art would have a reasonable expectation of success in treating hyperphagia and increased appetite using the heteroarl pyrrolidinyl ketone derivatives of Iyer.
Claim 26 is directed to the method of claim 1, wherein the manifestation of the behavior occurs at least once daily, optionally wherein the manifestation of the behavior persists for at least a week, optionally wherein the manifestation of the behavior persists for at least two weeks, optionally wherein the manifestation of the behavior persists for at least a month, optionally wherein the manifestation of the behavior persists for at least three months, optionally wherein the manifestation of the behavior occurs periodically.
The combined teachings of Iver, Rao, and Drejer are discussed above and incorporated herein by reference.
Rao further teaches administration of the triple uptake inhibitor for the treatment of atypical depression symptoms wherein the atypical depression is characterized by mood reactivity and neurovegetative symptoms present for more than about two weeks. Rao further teaches that the therapy can be prophylactic and be administered prior to bedtime to avoid the sleep disturbances associated with atypical depression secondary to pain. Accordingly, prophylactic administration prior to bedtime accounts for treating behaviors that manifest at least once daily.
Claim 34 is directed to a method of treating a subject who has been diagnosed with atypical depression, comprising administering a pharmaceutical composition comprising Compound 1, wherein the subject manifests one or more behavior selected from the group consisting of hypersomnia, hyperphagia, mood reactivity, leaden paralysis, low mood, interpersonal rejection sensitivity, rapid eating, recurrent episodes of binge eating, lack of control over eating, eating much more rapidly than normal, eating until feeling uncomfortably full, eating large amounts of food when not feeling physically hungry, eating alone because of feeling embarrassed by how much one is eating, feeling disgusted with oneself, depressed, or very guilty after overeating, marked distress regarding binge eating, binge eating not associated with compensatory behaviors, recurrent compensatory behaviors, binge eating with compensatory behavior, self-evaluation influenced by body shape and weight, purging type of recurrent compensatory behavior, non-purging type of recurrent compensatory behavior, refusal to maintain bodyweight at or above minimally normal weight, intense fear of gaining weight or becoming obese, disturbed by one's body weight or shape, self-worth influenced by body weight or shape, and persistent lack of recognition of seriousness of low bodyweight.
The teachings of Iyer, Rao, and Drejer are discussed above and incorporated herein by reference. Specifically, Iyer teaches compositions of compound 1 and methods of use thereof in treating a subject afflicted with depression and Rao teaches the use of non-tricyclic reuptake inhibitors as a treatment option for atypical depression.
Claim 35 is directed to a method of treating a subject manifesting at least one or more of a behavior selected from the group consisting of hypersomnia, hyperphagia, mood reactivity, leaden paralysis, low mood, interpersonal rejection sensitivity, rapid eating, recurrent episodes of binge eating, lack of control over eating, eating much more rapidly than normal, eating until feeling uncomfortably full, eating large amounts of food when not feeling physically hungry, eating alone because of feeling embarrassed by how much one is eating, feeling disgusted with oneself, depressed, or very guilty after overeating, marked distress regarding binge eating, binge eating not associated with compensatory behaviors, recurrent compensatory behaviors, binge eating with compensatory behavior, self-evaluation influenced by body shape and weight, purging type of recurrent compensatory behavior, non-purging type of recurrent compensatory behavior, refusal to maintain bodyweight at or above minimally normal weight, intense fear of gaining weight or becoming obese, disturbed by one's body weight or shape, self-worth influenced by body weight or shape, and persistent lack of recognition of seriousness of low bodyweight.
The teachings of Iyer, Rao, and Drejer are discussed above and incorporated herein by reference. Specifically, Iyer teaches compositions of compound 1 and methods of use thereof in treating a subject afflicted with depression and Rao teaches the use of non-tricyclic reuptake inhibitors as a treatment option for atypical depression.
Claim 36 is directed to a method of treating Prader-Willi syndrome in a subject in need, comprising administering a composition Compound 1, or a pharmaceutically acceptable salt thereof.
The teachings of Iyer, Rao, and Drejer are discussed above and incorporated herein by reference. Specifically, Iyer teaches compositions of compound 1 and methods of use thereof in treating a subject afflicted with depression and Drejer teaches methods of using triple reuptake inhibitors to treat Prader-Willi syndrome.
Conclusion
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/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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