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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/16/2025 has been entered.
Status of the Application
Claims 1, 3-5, 8, 10-12, 14-17, and 19-34 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 10/16/2025 are acknowledged. Claims under consideration in the instant office action are claims 1, 3-5, 8, 10-12, 14-17, and 19-34.
Applicants' arguments, filed 10/16/2025, have been fully considered and they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 1, 3-5, 8, 10-12, 14-17, and 19-34 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, "Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue', not 'experimentation'" (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations" (Wands, 8 USPQ2d 1404). Among these factors are: (i) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to administering a method of treating schizophrenia in an adult patient who has Child-Pugh Class A comprising administering an oral daily dose of 60 mg of crystalline lumateperone tosylate.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
Vyas et al. is drawn towards an evaluation of lumateperone tosylate for the treatment of schizophrenia (see abstract). Vyas et al. teaches treating schizophrenia patients aged 18-60 years receiving 60 mg once daily, and that peak D2RO for 60 mg lumateperone was 39%, which is lower than other second-generation antipsychotics at their effective doses and probably contributes to the favorable safety and tolerability profile of lumateperone, with no clinically significant changes in vital signs, cardiometabolic measurements and a reduced risk for movement disorders and hyperprolactinemia (pg. 142, right column, first paragraph). Vyas et al. teaches that 'atypical' or second-generation antipsychotics such as risperidone can avoid side effects including weight gain and diabetes mellitus, which has led to a need for a drug with a benign adverse effect profile (pg. 140, left column, second and third paragraph). Vyas et al. teaches that at 60 mg, lumateperone also reduced PANSS positive symptom score of schizophrenia as compared to placebo (pg. 142, left column, first paragraph).
However, Vyas et al. is silent as to the efficacy of the administration of 60 mg of lumateperone for patients who have Child-Pugh Class A.
(5) The relative skill of those in the art:
Those of relative skill in the art are those with a level of skill of the authors of the references cites to support the examiner’s position (those with advanced degrees and the requisite experience in medicine).
(6) The amount of direction or guidance presented and (7) the presence of absence of working examples:
The specification provides working examples only for the safety of the administration of 60 mg of lumateperone regarding a number of adverse events for adult patients with schizophrenia generally (Example 1). Although Example 1 also includes pharmacokinetic data for specific patient populations with different levels of hepatic impairment as presented in Fig. 1, such data does not demonstrate that the change in clinical exposure to lumateperone in patients with mild hepatic impairment is significantly less than that for patients with moderate or severe hepatic impairment since the variance in such levels between the different levels of impairment overlap. Additionally, Example 1 does not provide a statistical basis to demonstrate any difference between the pharmacokinetic levels of the different patient populations. Thus, the specification has not provided guidance for the patient population suffering from schizophrenia who also have Child-Pugh Class A.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by Vyas et al. above, and the high unpredictability in the art as evidenced therein, and the lack of guidance provided by the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Response to Arguments
Applicant argues that “Figure 1 of therefore demonstrates that the change in clinical exposure to lumateperone in patients with mild hepatic impairment is significantly less than that for patients with moderate or severe hepatic impairment.” The Examiner respectfully disagrees since although Example 1 also includes pharmacokinetic data for specific patient populations with different levels of hepatic impairment as presented in Fig. 1, such data does not demonstrate that the change in clinical exposure to lumateperone in patients with mild hepatic impairment is significantly less than that for patients with moderate or severe hepatic impairment since the variance in such levels between the different levels of impairment overlap. Additionally, Example 1 does not provide a statistical basis to demonstrate any difference between the pharmacokinetic levels of the different patient populations. Thus, the specification has not provided guidance for the patient population suffering from schizophrenia who also have Child-Pugh Class A.
Conclusion
Claims 1, 3-5. 8, 10-17, and 19-34 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691