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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 August 24, 2026 has been reviewed by the examiner and entered of record in the file.
3. Claims 7-9 are newly added. Claim 6 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected invention, without traverse, there being no allowable generic or linking claim.
4. Claims 1-3 and 7-9 are under examination and are the subject of this office action.
Priority
5. Applicant has not filed an English language translation of foreign priority KR Application No. 10-2020-0002576. It is suggested that a certified translation of every foreign benefit application or Patent Cooperation Treaty (PCT) application not filed in English be submitted. See 35 U.S.C. 119(b)(3) and 372(b)(3) and 37 CFR 1.55(g)(3)(i) and 41.154(b). A showing of priority that relies on a non-English language application is prima facie insufficient to overcome an intervening reference if no certified translation of the application is on file. See 37 CFR 41.154(b) and 41.202(e).
Previous Claim Objections
6. Claim 2 was previously objected to because the compound structure of lisuride depicted as “Formula 1” is blurry and some of the lines are difficult to distinguish. In view of Applicant’s replacement of the compound structure of Formula 1, the previous objection is withdrawn.
Response to Amendment
7. The Declaration under 37 CFR 1.132 of August 24, 2026, submitted by Dr. Chan Young Shin (the “Shin Declaration”), is insufficient to overcome the previous rejection of claims 1-3 based upon Sebree et al. (WO 2007/117687 A2) as set forth in the last Office action because: the Shin Declaration is predicated on the argument that the “prevailing view” that dopamine antagonists, not agonists were the candidate therapies for autism spectrum disorder (ASD), and that dopamine agonists tended to induce or worsen ASD-relevant behaviors such a repetitive or stereotyped activity. The Shin Declaration references the three publications previously submitted by Applicant on December 10, 2025: Schlepsi et al., Hellings et al., and Paval (page 2 of 5). The Shin Declaration alleges that because Applicant teaches that apomorphine worsens pre-pulse inhibition and was used to induce ASD-relevant symptoms in otherwise normal mice, and Sebree groups the dopamine agonists apomorphine and lisuride together, then one skilled in the art would not have a reasonable expectation that lisuride would treat ASD (pages 3-4 of 5). The Shin Declaration concludes with the opinion that one of ordinary skill in the art, upon reading Sebree, would not have had a reasonable expectation of success in the administration of lisuride to treat ASD in a subject with ASD.
8. It is noted that while the Hellings reference and the Paval reference each suggest the use of dopamine antagonists for the treatment of autism spectrum disorder symptoms, these teachings do not negate the fact that Sebree also suggests lisuride for the treatment of autism in a subject with autism. And, Newman-Tancredi et al. (The Journal of Pharmacology and Experimental Therapeutics, 2002) teach that antiparkinson agents including lisuride are heterogenous, i.e., they act as mixed agonists and antagonists of dopamine, demonstrating both agonist and antagonist properties at subtypes of Dopamine D2-Like Receptor and a2-Adrenoceptor (see abstract, Table 1 at page 808, and under Conclusions at page 813).
9. Therefore, one of skill in the art, knowing that lisuride demonstrates dopamine antagonist activity as well as agonist activity, and in view of the teachings of Sebree, would have a reasonable expectation of success in the administration of lisuride to treat ASD in a patient in need thereof.
Maintained Claim Rejections - 35 USC § 103
10. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
11. Claims 1-3 remain rejected and claim 7 is newly rejected under 35 U.S.C. 103 as being unpatentable over Sebree and Siegel, WO 2007/117687 A2, as evidenced by Lord et al., Nat. Rev. Dis. Primers (2022).
Claim 1 is directed to a method of treating autism spectrum disorder comprising administering a pharmaceutical composition comprising lisuride or a pharmaceutically acceptable salt thereof to a subject in need thereof, (more specifically, lisuride:
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(claim 2)), and
wherein the autism spectrum disorder is accompanied by one or more symptoms selected from hyperactivity or social deficit (claim 3).
12. Sebree discloses a method of treating a dopamine associated state in a subject, in particular naming autism in a subgenus of eleven dopamine associated states (Claim 2), comprising administering to said subject an implant comprising a dopamine modulating compound (as a class of drugs), specifically naming the dopamine agonist lisuride in a subgenus of seventeen particular suitable dopamine agonists (Claim 5). Sebree teaches pharmaceutically acceptable salts, esters, prodrugs, and metabolites of the dopamine agonists (page 3, lines 19-20). Sebree teaches wherein the implant comprises the dopamine agonist and a polymer that is biocompatible to the human body (i.e., comprises a pharmaceutical composition comprised of the polymer and the dopamine agonist), i.e., “[i]n one embodiment, the implant is comprised of a polymer that is biocompatible. The term "biocompatible" includes polymers which are not toxic to the human body, are not carcinogenic, and do not significantly induce inflammation in body tissues,” (page 6, lines 14-16).
13. While Sebree does not exemplify a single disclosed method of treating autism in a subject in need thereof comprising administering a composition comprising lisuride to said subject, Claim 5 of Sebree embraces a method of treating autism comprising administering a dopamine agonist that is lisuride. Thus, in this case, when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is described' as that term is used in 35 U.S.C. § 102(a), in that publication."). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982).
14. Sebree teaches that the dopamine associated state to be treated is autism (page 2, lines 33-37). And, it is clear as evidenced by Lord et al. that autism is characterized by impairments in social communication (i.e., social deficits) and often accompanied by hyperactivity disorders:
“[m]anifestations of autism include impairments in social communication and interaction, sensory anomalies, repetitive behaviours and varying levels of intellectual disability (BOX 1). Together with these core symptoms, co-occurring psychiatric or neurological disorders are common in people with autism, of which hyperactivity and attention disorders (such as attention-deficit/hyperactivity disorder (ADHD)), anxiety, depression and epilepsy are fairly prevalent.
[emphasis added], (see page 2, third paragraph).
15. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to administer the known dopamine agonist lisuride, specifically taught as particularly suitable by Sebree, and would have had a reasonable expectation of success in treating an autistic subject in need thereof.
16. Regarding the comprehensive of the genus of “dopamine associated states” disclosed by Sebree, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQad 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.").
17. Additionally, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed...." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
As such, claims 1-3 are prima facie obvious.
CLAIM 7 is drawn to claim 1, and limits wherein the lisuride is an acid addition salt formed with an organic acid.
18. Sebree additionally teaches pharmaceutically acceptable acid addition salts of said dopamine modulating compounds, formed with organic acids:
“Pharmaceutically acceptable acid addition salts of the dopamine modulating compounds are also part of this invention. The salts are prepared by methods well known to the art and are formed with both inorganic or organic acids, for example: maleic, fumaric, benzoic, ascorbic, pamoic, succinic, bismethylenesalicylic, methane sulfonic, ethane di sulfonic, acetic, oxalic, propionic, tartaric, salicylic, citric, gluconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzenesulfonic, hydrochloric, hydrobromic, sulfuric, cyclohexylsulfamic, phosphoric and nitric acids. The hydrohalic salts may be conveniently used.” (Page 4, lines 7-14).
As such, one of skill in the art before the effective filing date of the claimed invention would have reasonably considered preparing a pharmaceutically acceptable acid addition salt of lisuride, with an organic acid, as guided by Sebree, with a reasonable expectation of success.
Thus, claim 7 is prima facie obvious.
Response to Arguments
19. Applicant traverses the previous obviousness rejection of claims 1-3 over Sebree as evidenced by Lord et al., and argues the following:
Applicant references the opinion declaration submitted under 37 CFR 1.132 by Dr. Chan Young Shin (the “Shin Declaration,” see paragraphs 6-8 above), and argues that the Shin Declaration in addition to previous comments of the response filed June 24, 2026 confirm that the obviousness rejection should be withdrawn, as there is no reasonable expectation of success. Applicant alleges that the “discovery that lisuride works to treat autism” was surprising and unexpected.
Applicant goes on to disagree with the Advisory Action, in particular the Office’s position that “...[t]he fact that Applicant cites three references that allegedly "teach away" from administering dopamine agonists for treating autism does not negate the fact that Sebree teaches the same compound instantly recited by Applicant (lisuride) for the treatment of the same condition: autism....”
Applicant references the Shin Declaration and alleges that it provides objective evidence that a person having ordinary skill in the art upon considering Sebree would not expect lisuride to be capable of treating an autism spectrum disorder:
“…the Sebree reference provides no data showing that lisuride treats autism spectrum disorders. Rather, and as explained in Applicant's previous response, Sebree provides no working example, no in vivo or in vitro data, and no mechanistic hypothesis for lisuride treating autism (or, for that matter, for any other specific dopamine-agonist / dopamine-associated-state pairing). The disclosure with respect to the lisuride/autism pairing is, at most, a passing mention in two long parallel lists of compounds.” (Applicant’s Remarks, page 5).
20. Applicant's arguments have been fully considered but they are not persuasive. Regarding Applicant’s argument that Sebree fails to disclose or suggest that lisuride can treat autism spectrum disorder (i.e., “provides no working example, no in vivo or in vitro data, and no mechanistic hypothesis for lisuride treating autism”), Sebree teaches and recites a limited genus of dopamine-associated states and specifically names autism: see Claim 1: “[a] method for treating a subject for a dopamine associated state, wherein said dopamine associated state is autism (Claim 2), comprising administering to said subject a biodegradable implant, wherein said implant comprises an effective amount of a dopamine modulating compound (wherein said dopamine modulating compound is a dopamine agonist (Claim 4) and wherein said dopamine agonist is lisuride (Claim 5), such that said subject is treated for said dopamine associated state.”
21. Sebree teaches a subgenus of 11 “dopamine associated state[s],” specifically naming the dopamine associated state of autism within said small subgenus of dopamine associated states, such that one skilled in the art would have immediately envisaged selecting lisuride for the treatment of autism spectrum disorder. And, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." 27 F.3d at 554, 31 USPQ2d at 1132.). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). In this case, Sebree teaches and recites a method for treating a dopamine associated state in a subject, specifically naming autism (Claim 2), comprising administering to said subject a biodegradable implant comprising an effective amount of a dopamine modulating compound, in particular a dopamine agonist (Claim 4), and specifically naming lisuride in small genus of dopamine agonists (Claim 5).
22. For the sake of argument, even if it was agreed that Sebree taught away from administering lisuride for the treatment of autism spectrum disorder, “[e]ven if a reference discloses an inoperative device, it is prior art for all that it teaches,” (Beckman Instruments v. LKB Produkter AB, 892 F.2d 1547 (Fed. Cir. 1989)). Therefore, “a non-enabling reference may qualify as prior art for the purpose of determining obviousness under 35 U.S.C. 103” (Symbol Techs. Inc. v. Opticon Inc., 935 F.2d 1569 (Fed. Cir. 1991)). Thus, Sebree’s suggestion of treating a dopamine associated state in a subject, specifically naming autism, comprising administering a dopamine modulating compound including lisuride to said subject, constitutes prior art.
23. Regarding the Hellings and Paval publications, referenced in the Shin Declaration, the fact that each reference teaches the use of dopamine antagonists for the treatment of autism spectrum disorder symptoms does not negate the fact that Sebree suggests lisuride in a small genus of compounds for the treatment of autism.
24. While the Hellings reference and the Paval reference each suggest the use of dopamine antagonists for the treatment of autism spectrum disorder symptoms, these teachings do not negate the fact that Sebree also suggests lisuride for the treatment of autism in a subject with autism. And, Newman-Tancredi et al. (The Journal of Pharmacology and Experimental Therapeutics, 2002) teach that antiparkinson agents including lisuride are heterogenous, i.e., they act as mixed agonists and antagonists antagonists of dopamine, demonstrating both agonist and antagonist properties at subtypes of Dopamine D2-Like Receptor and a2-Adrenoceptor (see abstract, Table 1 at page 808, and under Conclusions at page 813).
25. Thus, Applicant has not sufficiently distinguished the recited method of treatment from the prior art of record. One of skill in the art before the effective filing date of the claimed invention, knowing that lisuride demonstrates dopamine antagonist activity as well as agonist activity, and in view of the teachings of Sebree, would have a reasonable expectation of success in the administration of lisuride to treat ASD in a patient in need thereof.
New Claim Rejections - 35 USC § 103
26. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
27. Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Sebree and Siegel, WO 2007/117687 A2, as applied to claims 1-3, above, in view of McDonald and Horowski, (Eur Neurol 1983, cited on Applicant’s IDS of July 7, 2022), and further in view of the WIPO English machine translation of Lee et al., CN 102933107 B (published February 2, 2018).
Claim 1 is addressed in detail, above.
Claim 8 is drawn to claim 1, wherein the lisuride or pharmaceutically acceptable salt thereof is administered to the subject in an amount of 0.01 to 500 mg/day.
Claim 9 is drawn to claim 1, wherein the pharmaceutical composition comprising lisuride further comprises corn starch, lactose hydrate, and magnesium stearate.
28. Sebree teaches and recites the administration of lisuride for a limited genus of dopamine-associated states and specifically names autism: see Claim 1: “[a] method for treating a subject for a dopamine associated state, wherein said dopamine associated state is autism (Claim 2), comprising administering to said subject a biodegradable implant, wherein said implant comprises an effective amount of a dopamine modulating compound (wherein said dopamine modulating compound is a dopamine agonist (Claim 4) and wherein said dopamine agonist is lisuride (Claim 5), such that said subject is treated for said dopamine associated state.”
29. As such, Sebree suggests the administration of lisuride for the treatment of autism, but does not teach a dose amount of 0.01 mg to 500 mg/day.
30. Yet, McDonald summarizes studies demonstrating the successful oral administration of lisuride at dose amounts ranging from 0.4 mg/day up to at least 6 mg/day, see Table II (page 244). A dose range of from 0.4 mg/day up to at least 6 mg/day lies within the range of “an amount of 0.01 to 500 mg/day” required by claim 8. MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). And, "[a] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). >See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).
As such, one of skill in the art before the effective filing date of the claimed invention would have been motivated to orally administer lisuride in the recited dose amount of claim 8, as guided by McDonald, with a reasonable expectation of success.
31. Sebree does not teach a pharmaceutical composition comprising lisuride comprising corn starch, lactose hydrate, and magnesium stearate.
32. Yet, McDonald teaches oral administration of lisuride, and Lee et al. teach oral dosage forms (page 1, first paragraph) comprising lisuride (“lysuride”) (named at page 3, line 14 of the English translation). And, in this case, when the species is clearly named, the compound species is anticipated no matter how many other species are additionally named. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter.1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is described' as that term is used in 35 U.S.C. § 102(a), in that publication."). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982).
Lee et al. go on to teach that the oral dosage form includes or more carriers, including filing agents such as lactose hydrate (see page 6, “(3)”), lubricants such as magnesium stearate (see page 6, “(4)”) and wetting agents such as corn starch (see page 6, “(10)”).
33. Thus, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to administer lirsuride in an oral dosage form, wherein said dosage from comprises the carriers lactose hydrate, magnesium stearate, and corn starch, as guided by McDonald in view of Lee et al., with a reasonable expectation of success.
As such, claims 8 and 9 are prima facie obvious.
Conclusion
34. In conclusion, claims 1-3 and 6-9 are present in the application. Claim 6 is currently withdrawn from consideration as directed to a nonelected invention. Claims 1-3 and 7-9 are rejected. No claim is presently allowable.
35. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
