DETAILED ACTION
Notice of AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
The amendments filed 7/20/2026 have been entered.
Response to Arguments
Applicant’s arguments, filed 7/20/2026, have been fully considered.
Applicant first traverses the rejection of claim 1 under 35 U.S.C. 112(b) as being indefinite. As argued by Applicant, “[t]he recitation ‘suicidal behavior in the patient is not observed...’ would be understood by a person of skill in the art as meaning that no suicidal behavior is noted or reported during the relevant period” (Applicant Arguments, Page 5).
Applicant’s explanation does not clarify the claim language. Indeed, Applicant’s indication “that no suicidal behavior is noted or reported during the relevant period” could mean that (a) suicidal behavior is actively monitored/evaluated according to the method and, based on said active monitoring/evaluating, no suicidal behavior is noted or reported as being present; or that (b) suicidal behavior is not monitored/evaluated and thus no suicidal behavior is noted or reported even when present.
Applicant, however, further argues that “claim 1 as amended recites ‘wherein Columbia-Suicide Severity Rating Scale (C-SSRS) is used for evaluating the risk of suicidal behavior’” and, as such, “the claim currently amended is definite” (Applicant Arguments, Page 5).
The amendment does nothing to clarify the claim language. The recitation merely defines an additional step of evaluating the risk of suicidal behavior using the Columbia Suicide Rating Scale (C-SSRS) which is distinct from the limitation that “suicidal behavior in the patient is not observed”.
As such, the claim is MAINTAINED rejected.
Applicant next traverses the rejection of claims under 35 U.S.C. 103(a). Applicant first notes that the basis of the rejection “states that Ahmad does not report any observation of suicidal behavior” (Applicant Arguments, Page 6). However, as further argued by Applicant, “Ahmad does not report that suicidal behavior was not observed” and that “depressive symptoms were merely alleviated, not eliminated. A person of ordinary skill in the art would thus not understand Ahmad as disclosing a system in which no suicidal behavior was observed, merely one in which depressive symptoms were alleviated” (Applicant Arguments, Page 6).
However, the claims do not recite “a system in which no suicidal behavior was observed”. Rather, claim 1 recites “[a] method for managing or decreasing a risk of suicidal behavior in a patient... comprising maintaining a therapeutically effective concentration of endoxifen in the patient by administering a dose of about 8 mg of endoxifen citrate in an enteric coated tablet once per day for at least 21 days, to the patient”, wherein “the suicidal behavior in the patient is not observed during a period of the maintaining of the therapeutically effective concentration of endoxifen in the patient”.
As such, even assuming arguendo that claim 1 requires that the suicidal behavior in a patient undergoing treatment of bipolar I disorder be actively monitored/evaluated and, based on said active monitoring/evaluating, it is observed that no suicidal behavior is present, the claim merely mandates that “the suicidal behavior in the patient is not observed” – i.e., it is observed that no suicidal behavior in the patient is present – “during a period of maintaining of the therapeutically effective concentration of endoxifen in the patient”. Accordingly, even if suicidal behavior was actively observed in a patient undergoing treatment according to Ahmad et al, a single instance of the suicidal behavior not being observed in said patient would meet the claim limitation.
Of course, for the reasons discussed above and in the basis of the rejection of claim 1 under 35 U.S.C. 112(b), claim 1 does not require that the suicidal behavior in a patient undergoing treatment of bipolar I disorder be actively monitored/evaluated and, based on said active monitoring/evaluating, it be observed (i.e., determined) that no suicidal behavior is present. Rather, claim 1 also embraces a method wherein suicidal behavior is not monitored/evaluated and thus no suicidal behavior is observed (i.e., determined) even when present. Indeed, as argued by Applicant, “[t]he recitation ‘suicidal behavior in the patient is not observed...’ would be understood by a person of skill in the art as meaning that no suicidal behavior is noted or reported during the relevant period” (Applicant Arguments, Page 5). And as further argued by Applicant, “Ahmad neither assessed nor reported suicidal behavior” (Applicant Arguments, Page 7).
As such, it is evident that the method of Ahmad et al teaches the instantly claimed limitation “wherein the suicidal behavior in the patient is not observed during a period of the maintaining of the therapeutically effective concentration of endoxifen in the patient”.
Applicant also argues that “Ahmad... did not employ the C-SSRS” (Applicant Arguments, Page 7).
The argument is not found persuasive. As discussed in the basis of the rejection, Ahmad et al teach measuring “mean change from baseline to end of treatment in the... Columbia-Suicide Severity Rating Scale (C-SSRS) score” (Page 254, Column 2, “Efficacy and safety assessments”).
Lastly, Applicant argues that claim 1 has been amended to further recite “wherein the patient had the bipolar I disorder progress during or after treatment with the at least one drug”. And, as argued by Applicant, “Ahmad does not disclose a patient population in which the patient had bipolar 1 disorder progress during or after treatment with at least one drug selected from lithium, valproate, carbamazepine, or an antipsychotic” (Applicant Arguments, Page 8).
The argument is not found persuasive. As indicated by Holford (Transl Clin Pharmacol 27:123-126, 2019), “[d]isease progression describes the natural history of disease” (Abstract). Ahmad et al disclose a patient population comprising “patients who were diagnosed with BPD I... [and] previously treated with at least one of the drugs, viz., lithium, valproate, carbamazepine, or an atypical (except for clozapine) or typical antipsychotic at some time during the course of their bipolar illness” (Page 253, Column 2 “Patients”). It is evident that the patient population disclosed by Ahmad et al – which were previously treated with at least one drug selected from lithium, valproate, carbamazepine, or an antipsychotic and subsequently “diagnosed with BPD I” – entail a patient that had the bipolar I disorder “progress” during or after treatment with the at least one drug.
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.
Claim 1 is MAINTAINED rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites:
“A method for managing or decreasing a risk of suicidal behavior in a patient undergoing a treatment of bipolar I disorder comprising:
maintaining a therapeutically effective concentration of endoxifen in the patient by administering a dose of about 8 mg of endoxifen citrate in an enteric coated tablet once per day for at least 21 days, to the patient;
wherein the suicidal behavior in the patient is not observed during a period of the maintaining of the therapeutically effective concentration of endoxifen in the patient,
wherein Columbia-Suicide Severity Rating Scale (C-SSRS) is used for evaluating the risk of suicidal behavior,
wherein the patient has previously undergone treatment with at least one drug selected from lithium, valproate, carbamazepine, or an antipsychotic, and
wherein the patient had the bipolar I disorder progress during or after treatment with the at least one drug.”
The recitation that “the suicidal behavior in the patient is not observed during a period of the maintaining of the therapeutically effective concentration of endoxifen in the patient” renders the claim indefinite.
For example, the recitation could mean that (a) suicidal behavior is actively monitored/evaluated according to the method and, based on said active monitoring/evaluating, it is observed that no suicidal behavior is present; or that (b) suicidal behavior is not actively monitored/evaluated and thus no suicidal behavior is observed even when present.
As such, claim 1 is rejected as indefinite.
Claim Rejections - 35 USC § 102
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 1-5 and 9-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ahmad et al (Clin Transl Sci 9:252-259, 2016; of record) as evidenced by Shahid et al (“Columbia-Suicide Severity Rating Scale (C-SSRS)”. In: STOP, THAT and One Hundred Other Sleep Scales, Springer, New York, NY (2011)) and Holford (Transl Clin Pharmacol 27:123-126, 2019).
As amended, claim 1 recites:
“A method for managing or decreasing a risk of suicidal behavior in a patient undergoing a treatment of bipolar I disorder comprising:
maintaining a therapeutically effective concentration of endoxifen in the patient by administering a dose of about 8 mg of endoxifen citrate (more specifically, 8 mg (claim 14)) in an enteric coated tablet once per day for at least 21 days, to the patient;
wherein the suicidal behavior in the patient is not observed during a period of the maintaining of the therapeutically effective concentration of endoxifen in the patient,
wherein Columbia-Suicide Severity Rating Scale (C-SSRS) is used for evaluating the risk of suicidal behavior,
wherein the patient has previously undergone treatment with at least one drug selected from lithium, valproate, carbamazepine, or an antipsychotic, and
wherein the patient had the bipolar I disorder progress during or after treatment with the at least one drug.”
Ahmad et al teach administration of “[e]ndoxifen... orally as enteric coated tablets... 8 mg/day” (Page 253, Column 2, “Methodology”; see also Page 253, Column 1, Figure 1, depicting endoxifen citrate) to “patients who were diagnosed with BPD I... [and] previously treated with at least one of the drugs, viz., lithium, valproate, carbamazepine, or an atypical (except for clozapine) or typical antipsychotic at some time during the course of their bipolar illness” (Page 253, Column 2 “Patients”) “for 21 days” (Page 253, Column 2 “Methodology”).
Regarding the recitation that the suicidal behavior in the patient is not observed during a period of the maintaining of the therapeutically effective concentration of endoxifen in the patient: nowhere do Ahmad et al report any observation of suicidal behavior.
Regarding the recitation that the Columbia-Suicide Severity Rating Scale (C-SSRS) is used for evaluating the risk of suicidal behavior: Ahmad et al further teach measuring “mean change from baseline to end of treatment in the... Columbia-Suicide Severity Rating Scale (C-SSRS) score” (Page 254, Column 2, “Efficacy and safety assessments”).
And, as evidenced by, Shahid et al, “[t]he C-SSRS was designed to provide a prospective, standardized measure of suicidality... and can be used to... establish suicide risk” (Page 131, Column 1).
As such, it is evident that the step of measuring “mean change from baseline to end of treatment in the... Columbia-Suicide Severity Rating Scale (C-SSRS) score” taught by Ahmad et al entails using the C-SSRS for evaluating the risk of suicidal behavior.
And, regarding the recitation that the patient had the bipolar I disorder progress during or after treatment with the at least one drug drug selected from lithium, valproate, carbamazepine, or an antipsychotic: Ahmad et al disclose a patient population comprising “patients who were diagnosed with BPD I... [and] previously treated with at least one of the drugs, viz., lithium, valproate, carbamazepine, or an atypical (except for clozapine) or typical antipsychotic at some time during the course of their bipolar illness” (Page 253, Column 2 “Patients”).
And, as evidenced by Holford, “[d]isease progression describes the natural history of disease” (Abstract).
As such, it is evident that the patient population disclosed by Ahmad et al – which were previously treated with at least one drug selected from lithium, valproate, carbamazepine, or an antipsychotic and subsequently “diagnosed with BPD I” – entail a patient that had the bipolar I disorder “progress” during or after treatment with the at least one drug.
Accordingly, claims 1 and 14 are anticipated.
Claims 2-3 are drawn to the method of claim 1, wherein the patient has manic episodes with mixed features (claim 2) or manic episodes without mixed features (claim 3).
Ahmad et al further teach that “patients... were diagnosed of BPD I and having displayed an acute manic or mixed episode (with or without psychotic features) according to DSM-IV-TR” (Page 252, Column 2, “Patients”).
Accordingly, claims 2-3 are also anticipated.
Claims 4-5 are drawn to the method of claim 1, wherein the patient has depression (claim 4) or depressive episodes (claim 5).
Ahmad et al teach that the “patients... were diagnosed of BPD I and having displayed an acute manic or mixed episode (with or without psychotic features) according to DSM-IV-TR” (Page 252, Column 2, “Patients”) and, when “depressive symptoms were assessed with the MADRS score throughout the trial”, “[t]he result indicated the effectiveness of endoxifen... 8 mg in alleviating depressive symptoms of mixed episode of BPD” (Page 256, Column 1, “Efficacy”).
As such, it is evident that the patients treated according to Ahmad et al suffered from depression and depressive episodes.
Accordingly, claims 4-5 are also anticipated.
New claim 9 recites:
“A method for managing or decreasing a risk of suicidal behavior in a patient undergoing a treatment of bipolar I disorder comprising:
maintaining a therapeutically effective concentration of endoxifen in the patient by administering a dose of about 8 mg of endoxifen citrate in an enteric coated tablet once per day for at least 21 days, to the patient;
evaluating the patient for a risk of suicidal behavior with a Columbia-Suicide Severity Rating Scale (C-SSRS) during the 21 days (more specifically, on a first day and on a second day of the 21 days, wherein the second day is at least 7 days after the first day (claim 10)); and
wherein the risk of suicidal behavior in the patient is not observed in the C-SSRS during the 21 days,
wherein the patient has previously undergone treatment with at least one drug selected from lithium, valproate, carbamazepine, or an antipsychotic, and
wherein the patient had the bipolar I disorder progress during or after treatment with the at least one drug.
The facts of Ahmad et al as evidenced by Shahid et al and Holford have been set forth above.
However, although Ahmad et al teach evaluating the patient for a risk of suicidal behavior with a Columbia-Suicide Severity Rating Scale (C-SSRS) during the 21 days (more specifically, on a first day and on a second day of the 21 days, wherein the second day is at least 7 days after the first day), Ahmad et al do not disclose that “the risk of suicidal behavior in the patient is not observed in the C-SSRS during the 21 days” as instantly claimed.
Yet, as indicated by the court in Hoffer v. Microsoft Corp., 405 F.3d 1326 (Fed. Cir. 2005), a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373 (Fed. Cir. 2003)). In the instant case, the wherein clause (i.e., wherein the risk of suicidal behavior in the patient1 is not observed in the C-SSRS during the 21 days) simply expresses the intended result of a process step positively recited (i.e., evaluating said patient for a risk of suicidal behavior with a Columbia-Suicide Severity Rating Scale (C-SSRS)). As such, the wherein clause is not given patentable weight.
Accordingly, claims 9-10 are also anticipated.
Claims 11-13 are drawn to the method of claim 9, wherein the step of evaluating the patient for the risk of suicidal behavior comprising asking the patient a first and second question from the C-SSRS during the 21 days (claim 11), more specifically wherein the first question comprises a first inquiry of the patient having thoughts of being dead and the second question comprises a second inquiry of the patient having thoughts of suicide (claim 13), and further comprising recording only negative indications for the patient for the first and second question (claim 12).
As evidenced by Shahid et al, the first question on the C-SSRS asks “[h]ave you wished you were dead or wished you could go to sleep and not wake up?”, and the second question asks “[h]ave you actually had any thoughts of killing yourself?” (Page 133).
Regarding the recitation wherein the step of evaluating further comprises recording only negative indications for the patient for the first and second question of the C-SSRS during the 21 days: in the instant case, the wherein clause (i.e., wherein only negative indications to the first and second question from the C-SSRS are recorded for the patient2) simply expresses the intended result of a process step positively recited (i.e., evaluating said patient for a risk of suicidal behavior with a Columbia-Suicide Severity Rating Scale (C-SSRS) comprising asking the patient the first and second question from the C-SSRS). As such, the wherein clause is not given patentable weight.
Accordingly, claims 11-13 are also anticipated.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,376,479 in view of Ahmad et al (Clin Transl Sci 9:252-259, 2016; of record).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘479 patent recites “[a] method of delivering endoxifen to the plasma of a subject, comprising orally administering to the subject an enteric-coated tablet... containing... an amount of a synthetic preparation of endoxifen... wherein... endoxifen is in the form of a citrate salt”.
It would have been obvious to apply the administration of endoxifen citrate as an enteric-coated tablet taught by the ‘479 patent in the treatment of a patient having BPI as claimed based on Ahmad et al, which specifically teach the administration of 8 mg/day endoxifen citrate as an enteric-coated tablet for 21 days in the treatment of a patient having BPI as claimed. And, given the concern that “a switch to depression remains a concern in all treatments of bipolar mania”, as recognized by Ahmad et al (Page 256, Column 1, “Efficacy”), it would have been obvious to evaluate the risk of suicidal behavior in said patients using the Columbia-Suicide Severity Rating Scale, as further taught by Ahmad et al ( Page 254, Column 2, “Efficacy and safety assessments”).
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,672,758 in view of Ahmad et al (Clin Transl Sci 9:252-259, 2016; of record).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘758 patent recites a method comprising “delivering endoxifen to the plasma of [a] subject... comprising orally administering to the subject an enteric-coated tablet... containing... an amount of a synthetic preparation of endoxifen... wherein... endoxifen is in the form of a citrate salt”.
It would have been obvious to apply the administration of endoxifen citrate as an enteric-coated tablet taught by the ‘758 patent in the treatment of a patient having BPI as claimed based on Ahmad et al, which specifically teach the administration of 8 mg/day endoxifen citrate as an enteric-coated tablet for 21 days in the treatment of a patient having BPI as claimed. And, given the concern that “a switch to depression remains a concern in all treatments of bipolar mania”, as recognized by Ahmad et al (Page 256, Column 1, “Efficacy”), it would have been obvious to evaluate the risk of suicidal behavior in said patients using the Columbia-Suicide Severity Rating Scale, as further taught by Ahmad et al ( Page 254, Column 2, “Efficacy and safety assessments”).
Conclusion
The new ground(s) of rejection presented in this Office action are necessitated by Applicant’s amendments to the claims. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
1 a patient undergoing a treatment of bipolar I disorder and being administered a dose of about 8 mg of endoxifen citrate in an enteric coated tablet once per day for at least 21 days, wherein the patient is evaluated for a risk of suicidal behavior with a Columbia-Suicide Severity Rating Scale (C-SSRS))
2 a patient undergoing a treatment of bipolar I disorder and being administered a dose of about 8 mg of endoxifen citrate in an enteric coated tablet once per day for at least 21 days, wherein the patient is evaluated for a risk of suicidal behavior with a Columbia-Suicide Severity Rating Scale (C-SSRS) comprising a first inquiry on having thoughts of being dead and a second inquiry on having thoughts of suicide )
Prosecution Insights