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 .
Detailed Action
Information Disclosure Statement
The information disclosure statement, size assertion, and size assertion fee are acknowledged. The IDS submitted 07/10/2025 has been considered.
Species Election
Applicant has elected the following species for search and examination:
Elected Compound
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Status of Claims
Claims currently pending and under examination are claims 8-13 and 26-31.
Response to Amendments
The amendments made to the claims 07/10/2025 have been entered.
The amendments made to the specification are considered new matter.
The amendment made to the specification removes “prevention” from the definition of treating. The amendment changes the scope of the term “treatment” and also the scope of the claim. Therefore, the amendment to the specification is not entered.
Modified Rejections
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 8-13 and 26-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treatment, does not reasonably provide enablement for prevention. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The following Wands factors have been considered if not explicitly discussed: (A) The breadth of the claims, (B) The nature of the invention, (C) The state of the prior art, (D) The level of one of ordinary skill, (E) The level of predictability in the art, (F) The amount of direction provided by the inventor, (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The term “treatment” is defined on page 36, l. 25-35 of the specification and said definition also embraces prevention.
It is presumed “prevention” of the claimed condition would require a method of identifying those individuals who will develop the claimed condition before they exhibit symptoms.
The factors to be considered in making an enablement rejection were summarized above. 1) preventing diseases requires identifying those patients who will acquire the condition before the symptoms occurs. This would require extensive and potentially opened ended clinical research on healthy subjects. 2) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical pharmacology and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will develop attention deficit hyperactivity disorder before the fact. 6) The artisan using Applicants invention would be a Board Certified physician. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of attention deficit hyperactivity disorder. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent ADHD. 7) It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed conditions
As claims 8-13 and 26-29 depend upon claim 8, they are also rejected.
Claim Rejections - 35 USC § 102/103
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.
Claim(s) 8-13 and 26-31 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Edison (Oryzon Genomics, Press Release GlobeNewswire, published July 18, 2018) and as evidenced by MayoClinic (Adult attention-deficit/hyperactivity disorder (ADHD), url = https://www.mayoclinic.org/diseases-conditions/adult-adhd/symptoms-causes/syc-20350878, accessed 10/15/2025, published 08/15/2017).
Claim 8 states “A method for treating one or more non-aggressive symptoms of attention deficit hyper activity disorder in a patient, comprising administering to the patient a therapeutically effective amount of a KDM1A inhibitor.”
Edison in sec. Basket trial – novel concept in psychotherapeutics R&D states “Oryzon believes it can employ a similar strategy to develop ORY-2001 for neuropsychiatric disorders due to observed holistic effect on aggression and behavior in preclinical models with LSD1/MAOB inhibition…Aggression is one of the more widespread alterations in patients with neurodegenerative and developmental disorders, as well as social withdrawal and depression. To establish a more specific psychiatric setting where ORY-2001 could be used Oryzon plants to initiate a Phase IIa trial…and [enroll] at least six patients per each indication: Alzheimer’s dementia, dementia with Lewy bodies, attention deficit hyperactivity disorder, autism spectrum disorder and borderline personality disorder.
The specification on p. 38 (shown above) indicates the structure and alternative naming of ORY-2001 which is claimed in claim 11.
Claim 8 specifies “non-aggressive” symptoms. However, as discussed by MayoClinic in sec. Overview, “Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that includes a combination of persistent problems, such as difficulty paying attention, hyperactivity and impulsive behavior.” MayoClinic in sec. Symptoms lists a number of symptoms that include impulsiveness, disorganization, prioritization, poor time management skills, focusing on a task, trouble multitasking, excessive activity, poor planning, low frustration tolerance, frequent mood swings, completing tasks, hot temper, difficulty coping with stress.”
Note symptoms range from non-aggressive symptoms such as disorganization (as exemplified in the specification, p. 3, l. 9-23) to aggressive symptoms such as hot temper and low frustration tolerance. One of ordinary skill in the art associate the various symptoms together such that treatment of one symptom would affect the other. If a patient receives treatment that would improve an aggressive symptom such as “low frustration tolerance”, then symptoms such as “focusing on a task” would also improve.
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(s) 8-13 and 26-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alemany (WO2019/025588, published 02/07/2019, filed 08/03/2018) as evidenced by MayoClinic (Adult attention-deficit/hyperactivity disorder (ADHD), url = https://www.mayoclinic.org/diseases-conditions/adult-adhd/symptoms-causes/syc-20350878, accessed 10/15/2025, published 08/15/2017).
In regards to claims 8, 10-11, 13, 29, and 30-31, Alemany o p. 1, sec Summary of the Invention states that the invention of its reference is drawn to methods for treating behavior alterations by using KDM1A inhibitors.” Alemany continues in l. 29-31 and states that a preferred KDM1A inhibitor is the 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine compounds or a pharmaceutically acceptable salt or solvate thereof.
Regarding the “behavior alterations” element, Alemany discusses “behavior” alterations” on p. 2, l. 28 where it states “…a behavior alteration relates, in particular, to an alteration, disturbance, dysfunction, aberration, disorder or the like affecting a subject’s behavior, including for example….behavior alterations induced by adverse social environment.” Alemany on p. 3, l. 1-12 expands on this where it states “in particular, this relates to an alteration, disturbance, dysfunction, aberration ,disorder or the like affecting a subject’s social behavior for whatever cause, including for example and without limitation, alterations in social behavior (e.g. social interactions alterations or aggressiveness)…” Alemany on p. 4, l. 10-29 connects “aggressiveness” to adult attention hyperactivity disorder (l. 24-25).
While the claims specify “non-aggressive symptoms”, MayoClinic in sec. Overview, “Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that includes a combination of persistent problems, such as difficulty paying attention, hyperactivity and impulsive behavior.” MayoClinic in sec. Symptoms lists a number of symptoms that include impulsiveness, disorganization, prioritization, poor time management skills, focusing on a task, trouble multitasking, excessive activity, poor planning, low frustration tolerance, frequent mood swings, completing tasks, hot temper, difficulty coping with stress.”
Note symptoms range from non-aggressive symptoms such as disorganization (as exemplified in the specification, p. 3, l. 9-23) to aggressive symptoms such as hot temper and low frustration tolerance. One of ordinary skill in the art associate the various symptoms together such that treatment of one symptom would affect the other. If a patient receives treatment that would improve an aggressive symptom such as “low frustration tolerance”, then symptoms such as “focusing on a task” would also improve.
In regards to claims 9, 26, 28, and 30-31 Alemany on p. 26, l. 16-19 defines “patient” to include humans.
In regards to claims 12, 27, 29, and 31, Alemany on p. 22-23, sec. Pharmaceutical Formulations contemplates oral deliver (p. 23, l. 5).
Alemany on p. 30, sec. 3.2 discusses the effects of administering the elected compound to SAMP8 mice lowered the aggressiveness of said mice.
Alemany teaches the elected KDM1A inhibitor compound and contemplates administration of the said compound to affect social behavior (attention deficit hyperactivity disorder) effectively.
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to take the compound of Alemany and apply it to methods of treating attention deficit hyperactivity disorder with a reasonable expectation of success. One of ordinary skill would find motivation in that Alemany teaches a direct effect of administering the compound.
Double Patenting Rejections
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.
18/451,897
Claims 8-13 and 26-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-10, 13-15, and 30-32 of copending Application No. 18/451,897 in view of Alemany (Cited above) as evidenced by MayoClinic (cited above).
The reference claims are drawn to methods of treating behavior alterations comprising administering a therapeutically effective amount of a KDM1A inhibitor. Reference claim 14 specifies the 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine.
The reference specification on p. 5 states “in some embodiments, the behavior alteration is aggressive associated with a disease. In some embodiments, said disease is a CNS disease. In some embodiments, said CNS disease is…adult attention deficit hyperactivity disorder.”
For similar reasoning as outlined in the 102/103 and the 103 rejections above, non-aggressive symptoms of ADHD are tied to aggressive symptoms and treatment for aggressive symptoms would improve non-aggressive symptoms.
This is a provisional nonstatutory double patenting rejection.
The rejections have been modified as necessitated by amendments made to the claims.
Response to Arguments
Applicant has amended the claims to specify “non-aggressive symptoms”.
In their arguments against the 102/103 rejection, applicant in their remarks submitted 07/10/2025 states “the therapeutic effect of ORY-2001 that is discussed in Edison and that is to be assessed in a planned clinical trial is a reduction in aggression, including in patients having ADHD.” Emphasis added by applicant. Applicant continues “there is absolutely no disclosure in Edison let alone any plausible teaching, that ORY-2001 would be therapeutically effective in the treatment of non-aggressive symptoms of DHD…”.
Applicant in their arguments against the 103 rejection states that “Alemany teaches nothing more than that KDM1A inhibitors exert a therapeutic effect against aggressiveness, including aggressive in patients with adult attention deficit hyperactivity disorder.” Applicant than points to Example 3 on p. 41, l. 12-20 of the instant specification, repeated below.
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Applicant then states that “the therapeutic efficacy of the KDM1A inhibitor vafidemstat specifically against non-aggressive symptoms of ADHD was thus determined separately and independently from its effect on aggressiveness in ADHD patient.” Applicant also states that aggression was also measured in Example 3.
The instant specification in example 3 does indeed state that aggression was measured. The instant specification in sec. 3.4 Results states “Treatment of ADHD patients with vafidemstat for 8 weeks produced a significant improvement in aggression, as shown by statistically significant reductions of the CGI-S and CGI-I values...”. Applicant continues “Unexpectedly, in addition to producing an improvement in aggression, the ADHD-RS score showed a statistically significant reduction after 2 months of treatment…” the ADHD-RS score is not tied to symptoms associated with aggression.
These results are acknowledged. However, as discussed in MayoClinic (cited above), symptoms of ADHD manifest in a wide array of symptoms. Two completely different behavioral symptoms, one being aggressive and the other being non-aggressive, can be expressed in the same patient. Essentially, non-aggressive and aggressive symptoms are connected and one of ordinary skill would expect improvement in non-aggressive symptoms if there is improvement in aggressive symptoms. The paragraph from example 3 above only shows that non-aggressive symptoms can be measured independently from aggressive symptoms. It has not been shown why one of ordinary skill would find the improvement unexpected considering that treatment of aggression in ADHD would affect both aggressive and non-aggressive symptoms.
The arguments are not persuasive and the rejections are maintained.
New Rejection
Claim Rejections - 35 USC § 112(b)
Claim 8-13 and 26-31, 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.
Claim 8 states “A method for treating one or more non-aggressive symptoms of…”.
This is repeated in claims 30 and 31.
The term “non-aggressive” is defined on p. 3, l. 11. The specification states “In accordance with the present invention, ‘non-aggressive’ as for example used in the context of a ADHD symptoms means that said symptom of ADHD is not directly related to or associated with aggression or aggressive behavior.” The specification on p. 3, l. 17 continues “Examples of non-aggressive symptoms of ADHD include…”.
As discussed in MayoClinic (cited above), symptoms of ADHD range widely. Certain symptoms also overlap in how they manifest (problems focusing on a task, poor time management skills, etc.). Additionally, symptoms including “poor time management skills”, “poor planning”, and “trouble coping with stress” are not found in the instant specification. Therefore, the listing of symptoms within the specification is open-ended and non-exhaustive.
One of ordinary skill in the art would not know from the present disclosure which symptoms are included within the claims and which symptoms are excluded. Therefore, one of ordinary skill in the art would not know the metes and bounds of the claims.
As claims 8-13 and 26-29 depend upon claim 8, they are also rejected.
Examiner’s Comments
Co-pending applications
Co-pending applications 19/174,254 and 19/242,350 are drawn to compounds of structure shown below
19/174,254 compound
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19/242,350 compound
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The elected species above embraces these compounds. However, the reference claims do not indicate that these compounds are KDM1A inhibitors.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624