DETAILED ACTION
This action is in response to papers filed on 06/27/2025. Claims 1-3, 9-10, 14-17, 19, 39, 40-47 of A. Bordbar 17/830,073 (06/01/2022) are pending examination on the merits: claim 40-48 are newly added, claims 1-2, 9-10, 14-17, and 39 are amended. Claims 1-3, 9-10, 14-17, 19, 39, 40-48 are rejected.
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 .
Priority
This application is a CON of PCT/US2020/062751 (12/01/2020) which claims benefit of 62/942,645 (12/02/2019).
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 06/27/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Applicant’s Amendments
Applicant has amended claims 1-2, 9-10, 14-17, and 39 and claims 40-47 are newly added. Applicant has amended the claims to include that the subject has Parkinson’s disease, schizophrenia, or Attention-Deficit/Hyperactivity Disorder. Applicant has also amended the claims to further include deuterated trapidil. Applicant’s amendment and newly added claims are acknowledged. Applicant’s Remarks at page 5.
Withdrawn Rejections
The following rejections are withdrawn:
The rejection of claims 1-19 under 35 USC § 112 – Scope of Enablement in view of Applicant’s amendment to claim 1. Applicant’s Remarks at pages 5 and 6.
The rejection of Claims 2-3, 5, 7-10, 12-14, and 16-18 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, in view of Applicant’s amendment and cancelations. Applicant’s Remarks at page 6.
The rejection of claim 18 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, in view of Applicant’s cancelation of claim 18. Applicant’s Remarks at 6.
The rejection of claims 1-3, 9-10, 14-17, 19, 39, 40-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33-34, 36-40, 44, and 51 of US 2018/0243307 A1 (‘307), in view of Strassnig and McDaniel. Applicant’s argument that ‘307 has been issued as the ‘212 patent was found to be persuasive.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Currently, there are two claim 42.
Misnumbered claim 42 been renumbered 43;
Claim 43 is renumbered claim 44;
Claim 44 is renumbered claim 45;
Claim 45 is renumbered claim 46; and claim 47 is renumbered claim 48.
Modified 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.
Claims 1-3, 9-10, 14-17, 19, 39, and 40-48 are rejected under 35 U.S.C. 103 as being unpatentable over Bordbar, US 2018/0243307 A1 (Pub: August 30, 2018) (“Bordbar), view of Strassnig et al., CNS Spectrums. 2018;23(6):370-377 (“Strassnig”) and Wu et al., Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:71-7 (“Wu”).
Regarding claim 1, Bordbar teaches methods for the prevention or treatment of extrapyramidal syndromes, for example, tardive dyskinesia (“TD”) or drug-induced Parkinsonism, “with the administration of a therapeutic effective amount of Trapidil, a derivative, a metabolite, a prodrug, an analog, or a pharmaceutically acceptable salt thereof.” Bordbar: Abstract, and para. [0004]. Bordbar also discusses in Example 7: Clinical Study Trapidil in Tardive Dyskinesia, where part of the criteria to be included in the study was that participants had to have a “Diagnosis of schizophrenia / schizoaffective disorder according to DSM-IV criteria…” [para. [0300], further highlighting a clinical association between TD and schizophrenia and the use of trapidil within the cognitive domain. Bordbar also teaches the use of deuterated trapidil as disclosed in para. [0031], similar to the claimed invention’s use of deuterated trapidil.
Strassnig teaches that “Tardive dyskinesia (TD) is a syndrome that subsumes a variety of iatrogenic movement disorders. It is mostly caused by antipsychotic medications to treat schizophrenia and other major mental disorders…”, and thus a known and clinically relevant problem (Strassnig’s Introduction). Strassnig also teaches that, “A large proportion of patients with chronic mental illness suffer from various degrees of TD” (i.e., tardive dyskinesia). More specifically, Strassnig teaches that patients suffering from mental illnesses such as depression, schizophrenia, bipolar disorder, autism, and even attention deficit hyperactivity disorder are likely to develop TD. Strassnig: Abstract. Strassnig also teaches that “There is a plethora of literature available that associates tardive dyskinesia with cognitive impairments…” (page 4). As discussed by Strassnig on page 5, “More recent evidence continues to implicate orofacial TD with greater cognitive impairment as compared to those without TD, including specific memory impairment that was associated with orofacial TD”.
Wu teaches in the Abstract and title that “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia”.
While the prior arts individually do not explicitly disclose the use trapidil to treat cognitive impairment in subjects having schizophrenia or Parkinson’s Disease, or Attention-Deficit/Hyperactivity Disorder (ADHD) per claim 1, one of ordinary skill in the art would be motivated to combine the teachings of Bordbar, Strassnig and Wu, with reasonable expectation of success, and arrive at the claimed invention. Wu teaches that TD is associated with greater cognitive impairment in schizophrenia. Bordbar’s teaches the use of trapidil in treating tardive dyskinesia (“TD”), and drug-induced Parkinsonism (Bordbar’s Abstract). Strassnig teaches that traditive dyskinesia (“TD”) is particularly prevalent in patients suffering from mental illnesses such as schizophrenia, and depression, as newer antipsychotic medications “and their liberal prescription might lead to emergence of new TD in patient populations previously less exposed to antipsychotics…” (Strassnig’s Abstract). Strassnig also teaches that TD is mostly caused by antipsychotic medications to treat not only schizophrenia, but other major mental disorders such as ADHD.
To one of ordinary skill in the art, given that TD is a known neuro/psychiatric movement-disorder indication, treatable with trapidil per Bordbar, and is predominantly most present in patients with schizophrenia and other mental disorders such as ADHD per Strassnig, and that TD is known to be associated with greater cognitive impairment in schizophrenia per Wu, it would be reasonable for one of ordinary skill in the art to use trapidil, already in use to treat TD, and explore using trapidil to treat cognitive impairment in subjects with mental disorders such as schizophrenia. Prior art Wu teaches “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia” and in view of Bordbar and Strassnig suggest that trapidil modulates the pathway through which TD manifests itself in patients with mental disorders such as schizophrenia, thus regulating cognitive impairment. One would therefore reasonably look at treating TD in schizophrenia, and other mental disorders such as Parkinson’s disease, or Attention-Deficit/Hyperactivity Disorder per claim 1 and arrive at the invention. One would have been motivated to do so in order to discover new use of trapidil, in not only treating traditive dyskinesia, but ultimately treat cognitive impairment in patients having schizophrenia or other mental disorders.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to first select Bordbar’s teachings of trapidil’s use, for example, as a treatment for tardive dyskinesia, and combine it with Strassnig and Wu’s teaching and arrive at the claimed method yielding no more than one would expect from such an arrangement. One would have been motivated to do so as a part of repurposing and finding new uses of trapidil based on its effects on treating extrapyramidal symptoms. Moreover, it must be noted that "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). MPEP § 2112(I). Claim 1 is therefore obvious over Bordbar, Strassnig and Wu.
Regarding claims 2-3, and 43, 45, Bordbar, Strassnig and Wu teaches the method of claim 1. Bordbar further teaches that trapidil as part of a combination therapy, including additional therapeutics such as dopamine precursor levodopa, antidepressants, anxiolytic, and antipsychotic agents. Bordbar at page 15, para. [0134]-[0138]. Claims 2-3, 43 and 45 as is claim 1, are also obvious.
Regarding claims 9-10, Bordbar, Strassnig and Wu. On page 5, Strassnig discusses that “More recent evidence continues to implicate orofacial TD with greater cognitive impairment as compared to those without TD, including specific memory impairment that was associated with orofacial TD…”. A deterioration of memory further suggests issues with word-finding, slowed thinking or slow speech. Claims 9-10 are therefore also obvious.
Regarding claim 14, Bordbar, Strassnig and Wu teaches the method of claim 1. Bordbar also teaches “exemplary pharmaceutically acceptable salts of Trapidil include, but are not limited to, salts with hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, ocalic acid, malonic acid, or tartaric acid.” Bordbar at page 11, para [0120]. Claim 14 is also obvious.
Regarding claims 15-17, 19 and 44, 46-48 Bordbar, Strassnig and Wu teaches the method of claim 1. Regarding the administration of trapidil, Bordhar discloses that “In some embodiments, Trapidil, a derivative, a metabolite, a prodrug, an analog, or a pharmaceutically acceptable salt thereof is administered orally. In some embodiments, the oral dose ranges from about 10 mg per day to about 3000 mg per day.” Bordbar at page 13, para [0131].
Bordbar teaches on page 1, para. [0004] that “In some embodiments, Trapidil, a derivative , a metabolite , a prodrug , an analog , or a pharmaceutically acceptable salt thereof and the additional therapeutic agent are administered sequentially…”, where the additional therapeutic agent may include dopamine precursor levodopa, antidepressants, anxiolytic, and antipsychotic agents. Bordbar at page 15, para. [0134]-[0138].
In Example 4 at para [0278] teaches the simultaneous administration of trapidil with haloperidol, an antipsychotic in an animal model. Bordbar discloses that: “Interactions between Trapidil and antipsychotics are determined by measuring plasma concentrations of the two compounds when administered together versus individually (Table 3).”
In Example 5, Bordbar teaches that “For prevention, Trapidil is co-administered with haloperidol over 10 weeks to five groups...”. Bordbar also teaches, a sequential administration process of haloperidol and trapidil, where “Trapidil is administered after rats have been treated with haloperidol for 10 weeks. At this point, Trapidil is co-administered at two doses to haloperidol treated groups for 3 weeks and symptoms are monitored every week during this period…” Bordbar at para [0283].
Regarding claim 19 recitation of “wherein the therapeutically effective dose comprises less than or equal to about 200 milligrams” falls within the range disclosed by Bordbar disclosed above: “from about 10 mg per day to about 3000 mg per day.” Bordbar at page 13, para [0131]. 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). Claims 15-17,19 44, and 46-48 are obvious.
Regarding claim 39, Bordbar, Strassnig and Wu teaches the method of claim 1. As disclosed above, Bordbar, Strassnig and Wu teach that TD, an extrapyramidal symotom, is associated with greater cognitive impairment in schizophrenia and is known to develop from overuse of antipsychotics. Bordbar discloses one such antipsychotic therapeutic haloperidol. In Fig. 1 and para [0010] Bordbar discloses “Trapidil's ability to ameliorate or reverse the expression changes in key genes related to
extrapyramidal syndromes induced by haloperidol, a potent first-generation antipsychotic…”. Claim 39 is therefore also obvious, and meets the limitation of “wherein the cognitive disorder is not caused by administration of levodopa.
Regarding claims 40-42, the claims are obvious over Bordbar, Strassnig and Wu using the same rationale as applied above to claim 1.
Applicant’s Arguments/Examiner’s Response
Applicant argues neither Bordbar or Strassnig alone or in combination teach the claimed invention. Applicant’s Remarks at pages 6. However, Applicant’s arguments are not found to be persuasive in view of the modified rejection above. The claims remain rejected as final in view of the teachings of Bordbar, Strassnig and Wu.
Modified 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, 9-10, 14-17, 19, 39, 40-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10350212 (‘212), in view of Strassnig et al., CNS Spectrums. 2018;23(6):370-377 (“Strassnig”), and Wu et al., Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:71-7 (“Wu”).
Claims 1-19 of ‘212 teaches a method of treatment or preventing a movement disorder in a subject in need thereof, comprising administering to the subject a therapeutic dose of trapidil, a derivative, a metabolite, or a pharmaceutically acceptable salt thereof, and levodopa; where the movement disorder is associated with Parkinson’s disease, and is manifested as a dyskinesia for example.
Similarly, the instant claims teach a method of treating of a cognitive impairment in a subject that has Parkinson’s disease, schizophrenia, or Attention-Deficit/Hyperactivity Disorder, comprising administering to the subject a therapeutically effective dose of: trapidil, deuterated trapidil, or a pharmaceutically acceptable salt thereof.
The difference between the claims of ‘212 and the instant application is that the instant application recites that the treatment of cognitive impairment in a subject that has Parkinson’s disease, schizophrenia, or Attention-Deficit/Hyperactivity Disorder (ADHD).
Strassnig teaches that “Tardive dyskinesia (TD) is a syndrome that subsumes a variety of iatrogenic movement disorders. It is mostly caused by antipsychotic medications to treat schizophrenia and other major mental disorders…”, and thus a known and clinically relevant problem (Strassnig’s Introduction). Strassnig also teaches that, “A large proportion of patients with chronic mental illness suffer from various degrees of TD” (i.e., tardive dyskinesia). More specifically, Strassnig teaches that patients suffering from mental illnesses such as depression, schizophrenia, bipolar disorder, autism, and even attention deficit hyperactivity disorder are likely to develop TD. Strassnig: Abstract. Strassnig also teaches that “There is a plethora of literature available that associates tardive dyskinesia with cognitive impairments…” (page 4). As discussed by Strassnig on page 5, “More recent evidence continues to implicate orofacial TD with greater cognitive impairment as compared to those without TD, including specific memory impairment that was associated with orofacial TD”.
Wu teaches in the Abstract and title that “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia”.
While the prior arts individually do not explicitly disclose the use trapidil to treat cognitive impairment in subjects having schizophrenia or Parkinson’s Disease, or Attention-Deficit/Hyperactivity Disorder (ADHD) per claim 1, one of ordinary skill in the art would be motivated to combine the teachings of ‘212, Strassnig and Wu, with reasonable expectation of success, and arrive at the claimed invention. Wu teaches that TD is associated with greater cognitive impairment in schizophrenia. ‘212 teaches the use of trapidil in treating tardive dyskinesia (“TD”), and drug-induced Parkinsonism (‘212 Abstract). Strassnig teaches that traditive dyskinesia (“TD”) is particularly prevalent in patients suffering from mental illnesses such as schizophrenia, and depression, as newer antipsychotic medications “and their liberal prescription might lead to emergence of new TD in patient populations previously less exposed to antipsychotics…” (Strassnig’s Abstract). Strassnig also teaches that TD is mostly caused by antipsychotic medications to treat not only schizophrenia, but other major mental disorders such as ADHD.
To one of ordinary skill in the art, given that TD is a known neuro/psychiatric movement-disorder indication, treatable with trapidil per ‘212, and is predominantly most present in patients with schizophrenia and other mental disorders such as ADHD per Strassnig, and that TD is known to be associated with greater cognitive impairment in schizophrenia per Wu, it would be reasonable for one of ordinary skill in the art to use trapidil, already in use to treat TD, and explore using trapidil to treat cognitive impairment in subjects with mental disorders such as schizophrenia. Prior art Wu teaches “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia” and in view of ‘212 and Strassnig suggest that trapidil modulates the pathway through which TD manifests itself in patients with mental disorders such as schizophrenia, thus regulating cognitive impairment. One would therefore reasonably look at treating TD in schizophrenia, and other mental disorders such as Parkinson’s disease, or Attention-Deficit/Hyperactivity Disorder and arrive at the invention. One would have been motivated to do so in order to discover new use of trapidil, in not only treating traditive dyskinesia, but ultimately treating cognitive impairment in patients having schizophrenia or other mental disorders.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to first select 212’s teachings of trapidil’s use, for example, as a treatment for tardive dyskinesia, and combine it with Strassnig and Wu’s teaching and arrive at the claimed method yielding no more than one would expect from such an arrangement. One would have been motivated to do so as a part of repurposing and finding new uses of trapidil based on its effects on treating extrapyramidal symptoms. Moreover, it must be noted that "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). MPEP § 2112(I). Claims 1-3, 9-10, 14-17, 19, 39, 40-47 are obvious over claims 1-19 of U.S. Patent No. 10350212 (‘212), in view of Strassnig et al., CNS Spectrums. 2018;23(6):370-377 (“Strassnig”), Wu et al., Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:71-7 (“Wu”).
Claims 1-3, 9-10, 14-17, 19, 39, 40-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11628170 A1 (‘170), in view of Strassnig et al., CNS Spectrums. 2018;23(6):370-377 (“Strassnig”), and Wu et al., Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:71-7 (“Wu”).
Claims 1-23 of ‘170 teaches a method of treatment or preventing Parkinson’s disease in a subject in need thereof, comprising administering to the subject a therapeutic dose of trapidil, a derivative, a metabolite, or a pharmaceutically acceptable salt thereof, and levodopa.
Similarly, the instant claims teach a method of treating of a cognitive impairment in a subject that has Parkinson’s disease, schizophrenia, or Attention-Deficit/Hyperactivity Disorder, comprising administering to the subject a therapeutically effective dose of: trapidil, deuterated trapidil, or a pharmaceutically acceptable salt thereof.
Strassnig teaches that “Tardive dyskinesia (TD) is a syndrome that subsumes a variety of iatrogenic movement disorders. It is mostly caused by antipsychotic medications to treat schizophrenia and other major mental disorders…”, and thus a known and clinically relevant problem (Strassnig’s Introduction). Strassnig also teaches that, “A large proportion of patients with chronic mental illness suffer from various degrees of TD” (i.e., tardive dyskinesia). More specifically, Strassnig teaches that patients suffering from mental illnesses such as depression, schizophrenia, bipolar disorder, autism, and even attention deficit hyperactivity disorder are likely to develop TD. Strassnig: Abstract. Strassnig also teaches that “There is a plethora of literature available that associates tardive dyskinesia with cognitive impairments…” (page 4). As discussed by Strassnig on page 5, “More recent evidence continues to implicate orofacial TD with greater cognitive impairment as compared to those without TD, including specific memory impairment that was associated with orofacial TD”.
Wu teaches in the Abstract and title that “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia”.
While the prior arts individually do not explicitly disclose the use trapidil to treat cognitive impairment in subjects having schizophrenia or Parkinson’s Disease, or Attention-Deficit/Hyperactivity Disorder (ADHD), one of ordinary skill in the art would be motivated to combine the teachings of ‘170, Strassnig and Wu, with reasonable expectation of success, and arrive at the claimed invention. Wu teaches that TD is associated with greater cognitive impairment in schizophrenia. ‘170 teaches the use of trapidil in treating Parkinson’s disease. Strassnig teaches that traditive dyskinesia (“TD”) is particularly prevalent in patients suffering from mental illnesses such as schizophrenia, parkinsonism and depression, as newer antipsychotic medications “and their liberal prescription might lead to emergence of new TD in patient populations previously less exposed to antipsychotics…” (Strassnig’s Abstract). Strassnig also teaches that TD is mostly caused by antipsychotic medications to treat not only schizophrenia, but other major mental disorders such as ADHD.
To one of ordinary skill in the art, given that TD is a known neuro/psychiatric movement-disorder indication, treatable with trapidil per ‘170, and is predominantly most present in patients with schizophrenia and other mental disorders such as ADHD per Strassnig, and that TD is known to be associated with greater cognitive impairment in schizophrenia per Wu, it would be reasonable for one of ordinary skill in the art to use trapidil, already in use to treat TD, and explore using trapidil to treat cognitive impairment in subjects with mental disorders such as schizophrenia. Prior art Wu teaches “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia” and in view of ‘170 and Strassnig suggest that trapidil modulates the pathway through which TD manifests itself in patients with mental disorders such as schizophrenia and Parkinson’s disease, thus regulating cognitive impairment. One would therefore reasonably look at treating TD in schizophrenia, and other mental disorders such as Parkinson’s disease, or Attention-Deficit/Hyperactivity Disorder and arrive at the invention. One would have been motivated to do so in order to discover new use of trapidil, in not only treating traditive dyskinesia, but ultimately treating cognitive impairment in patients having schizophrenia or other mental disorders.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to first select ‘170 teachings, and combine it with Strassnig and Wu’s teaching and arrive at the claimed method yielding no more than one would expect from such an arrangement. One would have been motivated to do so as a part of repurposing and finding new uses of trapidil based on its effects on treating extrapyramidal symptoms. Moreover, it must be noted that "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). MPEP § 2112(I). Claims 1-3, 9-10, 14-17, 19, 39, 40-47 are rejected as obvious over claims 1-23 of U.S. Patent No. 11628170 A1 (‘170), in view of Strassnig et al., CNS Spectrums. 2018;23(6):370-377 (“Strassnig”), and Wu et al., Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:71-7 (“Wu”).
Claims 1-3, 9-10, 14-17, 19, 39, 40-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-28 of U.S. 18/176,962 (US Patent. No. 12268691), in view of Strassnig et al., CNS Spectrums. 2018;23(6):370-377 (“Strassnig”), and Wu et al., Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:71-7 (“Wu”).
Claims 21-28 of ‘962 teaches a method of treatment or preventing levodopa-induced dyskinesia in a subject in need thereof, comprising administering to the subject a therapeutic dose of trapidil or a pharmaceutically acceptable salt thereof.
Similarly, the instant claims teach a method of treating of a cognitive impairment in a subject that has Parkinson’s disease, schizophrenia, or Attention-Deficit/Hyperactivity Disorder, comprising administering to the subject a therapeutically effective dose of: trapidil, deuterated trapidil, or a pharmaceutically acceptable salt thereof.
The difference between the claims of ‘962 and the instant application is that the instant application recites that the treatment of cognitive impairment in a subject that has Parkinson’s disease, schizophrenia, or Attention-Deficit/Hyperactivity Disorder (ADHD).
Strassnig teaches that “Tardive dyskinesia (TD) is a syndrome that subsumes a variety of iatrogenic movement disorders. It is mostly caused by antipsychotic medications to treat schizophrenia and other major mental disorders…”, and thus a known and clinically relevant problem (Strassnig’s Introduction). Strassnig also teaches that, “A large proportion of patients with chronic mental illness suffer from various degrees of TD” (i.e., tardive dyskinesia). More specifically, Strassnig teaches that patients suffering from mental illnesses such as depression, schizophrenia, bipolar disorder, autism, and even attention deficit hyperactivity disorder are likely to develop TD. Strassnig: Abstract. Strassnig also teaches that “There is a plethora of literature available that associates tardive dyskinesia with cognitive impairments…” (page 4). As discussed by Strassnig on page 5, “More recent evidence continues to implicate orofacial TD with greater cognitive impairment as compared to those without TD, including specific memory impairment that was associated with orofacial TD”.
Wu teaches in the Abstract and title that “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia”.
While the prior arts individually do not explicitly disclose the use trapidil to treat cognitive impairment in subjects having schizophrenia or Parkinson’s Disease, or Attention-Deficit/Hyperactivity Disorder (ADHD) per claim 1, one of ordinary skill in the art would be motivated to combine the teachings of ‘962, Strassnig and Wu, with reasonable expectation of success, and arrive at the claimed invention. Wu teaches that TD is associated with greater cognitive impairment in schizophrenia. ‘962 teaches the use of trapidil in treating tardive dyskinesia (“TD”). Strassnig teaches that traditive dyskinesia (“TD”) is particularly prevalent in patients suffering from mental illnesses such as schizophrenia, and depression, as newer antipsychotic medications “and their liberal prescription might lead to emergence of new TD in patient populations previously less exposed to antipsychotics…” (Strassnig’s Abstract). Strassnig also teaches that TD is mostly caused by antipsychotic medications to treat not only schizophrenia, but other major mental disorders such as ADHD.
To one of ordinary skill in the art, given that TD is a known neuro/psychiatric movement-disorder indication, treatable with trapidil per ‘962, and is predominantly most present in patients with schizophrenia and other mental disorders such as ADHD per Strassnig, and that TD is known to be associated with greater cognitive impairment in schizophrenia per Wu, it would be reasonable for one of ordinary skill in the art to use trapidil, already in use to treat TD, and explore using trapidil to treat cognitive impairment in subjects with mental disorders such as schizophrenia. Prior art Wu teaches “Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia” and in view of ‘962 and Strassnig suggest that trapidil modulates the pathway through which TD manifests itself in patients with mental disorders such as schizophrenia, thus regulating cognitive impairment. One would therefore reasonably look at treating TD in schizophrenia, and other mental disorders such as Parkinson’s disease, or Attention-Deficit/Hyperactivity Disorder and arrive at the invention. One would have been motivated to do so in order to discover new use of trapidil, in not only treating traditive dyskinesia, but ultimately treating cognitive impairment in patients having schizophrenia or other mental disorders.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to first select ‘962 teachings of trapidil’s use, for example, as a treatment for tardive dyskinesia, and combine it with Strassnig and Wu’s teaching and arrive at the claimed method yielding no more than one would expect from such an arrangement. One would have been motivated to do so as a part of repurposing and finding new uses of trapidil based on its effects on treating extrapyramidal symptoms. Moreover, it must be noted that "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). MPEP § 2112(I). Claims 1-3, 9-10, 14-17, 19, 39, 40-47 are obvious over claims 21-28 of 18/176,962 (‘962), in view of Strassnig et al., CNS Spectrums. 2018;23(6):370-377 (“Strassnig”), and Wu et al., Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:71-7 (“Wu”).
Applicant’s Arguments/Examiner’s Response
Applicant argues that the prior arts alone or in combination does not teach the claimed invention. Applicant’s Remarks at pages 6, and 9-10. However, Applicant’s arguments are not found to be persuasive in view of the modified 103 rejection above using the same rationale. The claims remain rejected as final in view of the teachings of Strassnig and Wu.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. 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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANTAL ADLAM whose telephone number is (571)270-0923. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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, JAMES HENRY ALSTRUM-ACEVEDO can be reached on (571) 272-5548. 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.
/C A/Examiner, Art Unit 1622 October 28, 2025
/DANAH AL-AWADI/Primary Examiner, Art Unit 1615