DETAILED ACTION
All rejections and objections not mentioned below are withdrawn.
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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. IT102020000007873, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. A claim by claim analysis indicated a lack of support for formula (I) and the genes of claim 7; thus all claims were given a priority date of 04/14/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/13/2022 and 12/11/2025 are being considered by the examiner.
Claim Rejections - 35 USC § 102- New Due to Amendments and New IDS
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 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)(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.
Claim(s) 1, 6-8, 10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ORTEGA (ORTEGA et al., EP2776394B1, 2018-12-26, IDS) as evidenced by PubChem (PubChem, Iadademstat, 2026) and as evidenced by Heuvel (Heuvel et al., Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine. . Toxins 2022, 14, 138) and as further evidenced by Vielle NJ et al., "The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses", Front Microbiol, 2019, 10:811.
The reference ORTEGA teaches “The compound of claim 1, the compound for use as a medicament according to claim 5 or the pharmaceutical composition of claim 7, wherein said compound is (trans)-N1-((1R,2S)-2-phenylcyclopropyl)cyclohexane-1,4-diamine, or a salt or solvate thereof”(reference claim 30) and “(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS”(title). This is iadademstat drawn below and as demonstrated by the structure, as
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evidenced by PubChem.
The reference ORTEGA teaches “A compound as defined in any of claims 1 to 6, 8, 10 to 30 or 32 or a pharmaceutically acceptable salt or solvate thereof or a compound as defined in claim 31 or the pharmaceutical composition of any of claims 7 to 32 for use in the treatment or prevention a viral infection or for use in the treatment or prevention of viral reactivation after latency” (reference claim 36) and “In still another aspect, the invention provides the use of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for the manufacture of a medicament for the treatment or prevention of a viral infection. In a preferred embodiment, said viral infection is a herpesvirus infection (e.g., a herpesvirus infection caused by and/or associated with a herpesvirus chosen from HSV-1, HSV-2, and Epstein-Barr virus) or a viral infection caused by and/or associated with HIV. In another preferred embodiment, said viral infection is caused by and/or associated with a Hepadnavirus, particularly Hepatitis B virus (HBV). In another embodiment, said viral infection is caused by and/or associated with a Flavivirus, particularly Hepatitis C virus (HCV), yellow fever virus, West Nile virus, Dengue virus or Japanese encephalitis virus, and more preferably HCV”[0047]. The reference Heuvel provides evidence that yellow fever virus, dengue virus and HIV are all RNA viruses. The reference Vielle provides evidence that Flaviviruses are also RNA viruses and that they are viral infections of the respiratory tract This anticipates claim 1, 6 and 10.
On page 6 of the instant specification iadademstat is mention to induce increased expression of inflammatory cytokines while sparing the expression of Interferon and Interferon-Stimulated Genes as in instant claim 7. This means this is inherent to iadademstat whether or not the property was known in the prior art. “Products of identical chemical composition cannot have mutually exclusive properties.” Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F. 2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). This anticipates claim 7.
The reference ORTEGA teaches “The active compounds can also be administered in combination with another active agent that synergistically treats or prevents the same symptoms or is effective for another disease or symptom in the patient treated so long as the other active agent does not interfere with or adversely affect the effects of the active compounds of this invention. Such other active agents include but are not limited to anti-inflammatory agents, antiviral agents, antibiotics, antifungal agents, antithrombotic agents, cardiovascular drugs, cholesterol lowering agents, anti-cancer drugs, hypertension drugs, and the like”[0386]. This anticipates claim 8.
The reference also teaches “Cyclopropylamine containing compounds are known to inhibit a number of medically important targets including amine oxidases like Monoamine Oxidase A (MAO-A; or MAOA), Monoamine Oxidase B (MAO-B; or MAOB), and Lysine Specific Demethylase-1 (LSD1). Tranylcypromine (also known as 2-phenylcyclopropylamine), which is the active ingredient of Parnate® and one of the best known examples of a cyclopropylamine, is known to inhibit all of these enzymes. Since MAO-A inhibition may cause undesired side effects, it would be desirable to identify cyclopropylamine derivatives that exhibit potent LSD1 inhibitory activity while being devoid of or having substantially reduced MAO-A inhibitory activity”[0006] and “The compounds of the invention are unexpectedly potent and selective inhibitors of LSD1. Avoiding inhibition of "off-targets" can avoid unwanted or undesirable side-effects like the cheese effect associated with MAO-A”[0372].
Claim Rejections - 35 USC § 103 - New Due to Amendments and New IDS
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) 1-2 and 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over ORTEGA (ORTEGA et al., EP2776394B1, 2018-12-26, IDS) in view of RAO (RAO et al., WO 2021195723 A1, Effective Filing Date: 04/03/2020, previous provided) as evidenced by PubChem (PubChem, Iadademstat, 2026) and as evidenced by Heuvel (Heuvel et al., Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine. . Toxins 2022, 14, 138) and as further evidenced by Vielle NJ et al., "The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses", Front Microbiol, 2019, 10:811.
The reference ORTEGA has been discussed supra and does not disclose Coronavirus (claims 2 and 11-12).
The reference ROA teaches “A method of treating a coronavirus infection in a subject having a coronavirus infection, the method comprising administering to the subject an agent that inhibits or reduces an activity of a lysine-specific demethylase 1 (LSD1) polypeptide, to thereby treat the coronavirus infection in the subject”(reference claim 1). The instant specification defines the following: “By "coronavirus infection" it is intended an infection caused by or otherwise associated with growth of coronavirus in a subject, in the family Coronaviridae (subfamily Coronavirinae)”(page 10).
The reference ROA teaches “In some embodiments, the agent is a selective LSD1 inhibitor. For example, the selective LSD1 inhibitor can be selected from the group comprising or consisting of GSK-LSD1 , SP-2509, and SP-2577” [0014] and “In some alternative preferred embodiments, the agent is SP-2509, which has the following molecular structure…” [0016]. The
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reference ROA teaches:
The reference ROA teaches “In yet another aspect, the invention provides a method of reducing or preventing entry of a coronavirus into a cell, the method comprising exposing the cell to an agent that inhibits an activity of a lysine-specific demethylase (LSD) polypeptide, to thereby antagonise, or otherwise reduce the level or amount of TMPRSS2 polypeptide present on the surface of the cell” [0010].
The reference ROA teaches “Thus, in accordance with the present invention, methods and compositions are provided that take advantage of an LSD1 inhibitor {e.g., a selective LSD1 inhibitor) to reduce or abrogate the transcription of integral cellular machinery required for a coronavirus entry into a cell. In some embodiments, the LSD1 inhibitor is used in combination with an additional antiviral agent. The methods and compositions of the present invention are thus particularly useful in the treatment or prophylaxis of a coronavirus infection {e.g., a coronavirus infection), as described hereafter” [0113].
The reference ROA teaches “Coronaviruses are enveloped RNA viruses that infect mammals and birds. The severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) are both members of the genus Betacoronavirus, and responsible for hundreds of deaths in Asia and the Middle East, respectively”[ 0003].
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified ORTEGA with ROA because they both teach LSD1 inhibitors for the treatment of RNA viruses. One would be motivated to use the LSD1 inhibitor iadademstat of ORTEGA in replacement of the LSD1 inhibitors of ROA because ORTEGA discloses that iadademstat combines the advantageous properties of a highly potent LSD1 inhibitory activity and a negligible MAO-A inhibitory activity[0372] while the Tranylcypromine as taught by ORTEGA [0006] and the LSD1 inhibitors of ROA [0216] are known to cause MAO-A inhibition which may cause undesired side effects[0006 Ortega]. One would have a reasonable expectation of success because iadademstat is a suggested LSD1 inhibitor for RNA viruses.
Claim(s) 1 and 4-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over ORTEGA (ORTEGA et al., EP2776394B1, 2018-12-26, IDS) in view of Vianello (Vianello et al., J. Med. Chem. 2016, 59, 1501−1517, previously provided) as evidenced by PubChem (PubChem, Iadademstat, 2026) and as evidenced by Heuvel (Heuvel et al., Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine. . Toxins 2022, 14, 138) and as further evidenced by Vielle NJ et al., "The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses", Front Microbiol, 2019, 10:811.
The reference ORTEGA has been discussed supra and does not disclose the compounds of claims 4-5.
The reference Vianello teaches “Discovery of a Novel Inhibitor of Histone Lysine-Specific Demethylase 1A (KDM1A/LSD1) as Orally Active Antitumor Agent”(title) and “In a previous manuscript, we showed that substitutions on the phenyl moiety of TCPA allowed the identification of highly active KDM1A inhibitors”(page 1502).
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This helps to teach claims 4 and 5.
The reference Vianello teaches “In particular three molecules (14d, 14e, and 14g) showing selectivity versus MAO A and remarkably inhibiting colony formation in THP-1 human leukemia cells, were assessed in mouse for their preliminary pharmacokinetic.”(abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified ORTEGA with Vianello because ORTEGA teaches LSD1 inhibitors for treating infections and Vianello also teaches LSD1 inhibitors so it would be obvious to substitute one LSD1 inhibitor for another since they are used for the same purpose of inhibiting LSD1. One would have a reasonable expectation of success because ORTEGA teaches LSD1 inhibitors with similar structures to the starting molecule for Vianello and Vianello teaches highly active derivatives. One would be motivated to do so to have LSD1 inhibitors that have less selectivity towards MAO A which can cause undesired side effects. One would have reasonable expectation of success do to the compound being a known LSD1 inhibitor.
Double Patenting - New Due to Amendments and New IDS
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 1-8 and 10-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. US 10233165 B2 in view of over ORTEGA (ORTEGA et al., EP2776394B1, 2018-12-26, IDS) in view of Vianello (Vianello et al., J. Med. Chem. 2016, 59, 1501−1517, previously provided) in view of RAO (RAO et al., WO 2021195723 A1, Effective Filing Date: 04/03/2020, previous provided) as evidenced by PubChem (PubChem, Iadademstat, 2026) and as evidenced by Heuvel (Heuvel et al., Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine. . Toxins 2022, 14, 138) and as further evidenced by Vielle NJ et al., "The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses", Front Microbiol, 2019, 10:811.
The patent ‘165 claims:
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The patent ‘165 does not teach the compound of claim 12 for the treatment of RNA viral infection (all claims).
The secondary references further teaches that all needed changes would be obvious as outlined in the 103 rejection (which is incorporated herein by reference).
It would have been prima facie obvious to one of ordinary skill in the art to have modified ‘165 with ORTEGA and Vianello because patent ‘165 teaches LSD1 inhibitors for treatment of RNA virus HIV and ORTEGA teaches LSD1 inhibitors for treating HIV infections and Vianello also teaches LSD1 inhibitors of the same structure as the patent ‘165 so it would be obvious to substitute one LSD1 inhibitor for another since they are used for the same purpose of inhibiting LSD1. One would have a reasonable expectation of success because Vianello teaches LSD1 inhibitors with similar structures to the starting molecule for Vianello and Vianello teaches highly active derivatives. One would be motivated to do so to have LSD1 inhibitors that have less selectivity towards MAO A which can cause undesired side effects as taught by ORTEGA.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified patent ‘165 and ORTEGA with ROA because they both teach LSD1 inhibitors for the treatment of RNA viruses. One would be motivated to use the LSD1 inhibitor iadademstat of ORTEGA in replacement of the LSD1 inhibitors of ROA because ORTEGA discloses that iadademstat combines the advantageous properties of a highly potent LSD1 inhibitory activity and a negligible MAO-A inhibitory activity[0372] while the Tranylcypromine as taught by ORTEGA [0006] and the LSD1 inhibitors of ROA [0216] are known to cause MAO-A inhibition which may cause undesired side effects[0006 Ortega]. One would have a reasonable expectation of success because iadademstat is a suggested LSD1 inhibitor for RNA viruses.
Response to Arguments
Applicant’s arguments with respect to claim(s) 12/11/2025 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
As for the unexpected results argument, these arguments are not persuasive because several of the claims are anticipated and thus cannot be overcome by unexpected results. Additionally, unexpected results must be commensurate in scope with the claims which the evidence is offered to support. The claims are not commensurate in scope with the unexpected results. For instance, the unexpected result is only for SARS-COV-2 which is only required by claim 12 and even then other options are given as alternatives. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
The double patenting rejection was rejecting for US 10233165 B2 as well not just the combination and no argument has been made against this specific rejection.
Conclusion
Claims 1-2, 4-8 and 10-12 are rejected.
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 12/11/2025 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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 ALISON AZAR SALAMATIAN whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.S./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627