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 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, 5-6, 9, 12-16, 18-19 and 21-31 are rejected under 35 U.S.C. 112, 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. Claims are enabled for treatment but not prevention of tremors and seizures. However, claims are not enabled for treatment or prevention of any other condition. Since there is a large number of diseases and conditions that fall within the scope of disease or condition relating to aberrant function or activity of T-type calcium channel, this rejection will focus on treatment and prevention of autism.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (a) the nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
Nature of the invention and Breadth of the claims:
Claims are directed to a method of treating a disease or condition relating to aberrant function or activity of T-type calcium channel in a subject in need. The breadth of diseases includes treatment of diseases for which no known treatment currently exists. For example, autism is linked to malfunction of T-type calcium channel.
Claims also encompass prophylactic administration, which is prevention of diseases or conditions. Paragraph [00061] of the specification defines treatment to include prophylactic administration before subject begins to suffer from a disease.
State of the prior art and level of predictability in the art:
Art does not recognize therapeutic intervention that results in treatment or prevention of autism. Current treatment options for subjects with autism involve applied behavior analysis, speech and language therapy, occupational and physical therapy.
Amount of direction provided by the inventor and existence of working examples: The Examples set forth in the instant demonstrate activity of the claimed compound in adults with generalized epileptic syndromes with absence seizures (Example 9) and essential tremor (Example 9). There are no prophylactic examples or any examples directed to treatment of subjects with autism.
Although, the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), lack of a working example is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
Relative skill of those in the art and quantity of experimentation needed to make or use the invention:
Although the relative level of skill in the art is high, one of ordinary skill would not be able to treat or prevent autism according to the claimed method without engaging in undue experimentation.
Thus, given these considerations, one of ordinary skill in the art clearly would not be able to practice the claimed method such that it can be used as contemplated in the specification without first engaging in substantial and undue experimentation. Therefore, the claims are rejected under 35 U.S.C. §112, first paragraph, as lacking and enabling disclosure.
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.
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.
Claim(s) 1-3, 5-6, 9, 12-16, 18-19, 21-25 and 30-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Reddy et al (WO 2018/118101; published 6/28/18).
Scope of prior art
Reddy teaches T-type calcium channel modulator Z944, which is the currently claimed compound of formula I (page 3, par 2). The teaching also includes pharmaceutically acceptable salts including HCl salt (page 16, line 1). Reddy teaches treatment of diseases and disorders via modulation of T-type calcium channel (page 6, last paragraph). The list of disorders includes epilepsy and tremors (page 32, line 7).
Reddy teaches dose increase based on EEG recording and/or blood analysis (page 4, lines 1-6) and provides an example where the agent is administered daily for a week at 20mg/day, then daily for a week at a higher amount (25–50mg), then daily for a week at yet a higher dose (45-70mg) (page 4, lines 7-12).
Regarding formulations Reddy teaches quick sustained or delayed formulations (p44, last paragraph).
Ascertaining the difference
Reddy teaches repeated dose escalations in the range of 20-70mg/day. However, Reddy does not teach the pharmacokinetic parameters such as AUC and Cmax associated with each dose. Nor does Reddy teach maximum titrated dose.
Reddy broadly teaches dose escalation and specifically teaches 3 different daily doses administered 1 week apart. However, Reddy does not recite up to 5 dose escalations or escalation after administration of a specific dose for 3 days.
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application would have found it obvious to determine through routine experimentation the optimal administration schedule of Z944 to a subject in need of treatment for epilepsy or tremors. Determining pharmacokinetic parameters such AUC and Cmax is routine and necessary in the art of pharmacology in order to obtain a safe and effective treatment regimen. It would have been obvious for a skilled artisan to determine the duration for administration of each successive dose and to determine the optimal number of dose escalations required to achieve the desired treatment outcome. While art teaches a week of administration for each dose, the broader teaching is not limited to a specific time period and experimenting with shorter and longer periods with the goal of optimizing treatment safety and efficacy would have been obvious to a skilled artisan.
Regarding maximum titrated dose. Maximum titrated dose represents the maximum safe dose administered to a subject. It would have been obvious to escalate dose amounts until the maximum safe dose is reached.
Claim(s) 26-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Reddy as applied to claim 1 above, and further in view of Majumder et al (Journal of Pharmacy and pharmacology, 2016, 4, 381-385).
Reddy does not teach HPMC as a polymer in extended-release formulation
Majumder teaches benefits of using HPMC in controlled release dosage form. (page 382, section 3).
Obviousness
Reddy teaches that various drug release systems can be utilized including extended, or controlled release (p44, last paragraph) and those systems are known to those skilled in the art. Majumder teaches benefits of using HPMC for controlled release formulations. It would have been obvious for a skilled artisan to use HPMC as a carrier polymer for an extended-release formulation comprising Z944. Majumder lists consumer acceptance and versatility as benefits of using HPMC thereby providing motivation to include it in a controlled release formulation.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-6, 9, 12-16, 18-19, 21-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-57 (amended claim set 9/23/25) of copending Application No. 18/864,098 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims of the ‘098 application are directed to a method of treating essential tremor comprising the currently claimed administration schedule including dose escalation following a predefined period.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-3, 5-6, 9, 12-16, 18-19, 21-31 are pending
Claims 1-3, 5-6, 9, 12-16, 18-19, 21-31 are rejected
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YEVGENY VALENROD whose telephone number is (571)272-9049. The examiner can normally be reached Mon-Fri 9am-5pm.
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, Amy L Clark can be reached at 571-272-1310. 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.
/YEVGENY VALENROD/Primary Examiner, Art Unit 1628