DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 38, 40, 43-44 and 46-47 are pending. Claims 38, 40, 43-44 and 46-47 are rejected.
Response to Arguments
In the remarks filed September 19th, 2025 Applicant traverses the obviousness rejection of claims 38-40, 43-44 and 46-47 stating that the claims have been amended and that “neither Reinhoff nor Carobbio teach or suggest a ‘method for maintaining leukocyte levels within a therapeutically beneficial range in a subject with myeloproliferative neoplasm,… wherein the periodically assessing and adjusting is at least as frequently as monthly’.” This argument is unpersuasive. While neither of the cited references explicitly teach a step wherein the platelet count of the subject is assessed and the dosage is adjusted accordingly as frequent as monthly, Reinhoff does teach a method of treating myeloproliferative neoplasms in a subject in need thereof, and for effecting specific clinically relevant endpoints (abstract). Additionally, Reinhoff states that dose level for a particular patient will depend on factors such as severity of the indication or condition being treated (paragraph [0171]) and teaches a once a week dosing frequency for the therapeutic regimen (paragraph [0170]). Carobbio teaches that prognostic risk of thrombosis in patients with essential thrombocythemia, a myeloproliferative neoplasm, is driven by a patient’s combination of white blood cell and platelet count. Accordingly, a person of ordinary skill performing the method of treating a myeloproliferative neoplasm, such as essential thrombocythemia, to maintain a leukocyte count within a therapeutically beneficial range by administering the LSD1 inhibitor as frequently as the once a week in the regimen disclosed by Rienhoff would have been motivated to monitor platelet count in the subject and adjust the dose appropriately prior to weekly re-administration to minimize the risk of thrombosis and optimize treatment outcomes. Such periodic assessment and adjusting would be routine to a person of ordinary skill performing a method of treatment to achieve particular clinically relevant levels for platelet counts and the like.
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.
Claims 38, 40, 43-44 and 46-47 are rejected under 35 U.S.C. 103 as being unpatentable over WO2017079753A1 by Rienhoff in view of Carobbio et al. Blood (2008) 112 (8): 3135–3137.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Rienhoff teaches “lysine-specific histone demethylase as a novel therapeutic target in myeloproliferative neoplasms” (title) and disclose (abstract):
methods for treating or preventing myeloproliferative neoplasms in a subject in need thereof, and for effecting specific clinically relevant endpoints, comprising administering a therapeutically effective amount of an LSD1 inhibitor.
Rienhoff discloses the LSD1 inhibitor of the instant claims (page 67):
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The prior art lists myeloproliferative neoplasms including essential thrombocythemia (paragraph [0294]). Rienhoff states that dose level for a particular patient will depend on factors such as severity of the indication or condition being treated (paragraph [0171]). Additionally, in paragraph [0170], the prior art discloses that the LSD1 inhibitor may be formulated for administration at any frequency of administration including once a week, and states:
[s]uch dosing frequency is also maintained for a varying duration of time depending on the therapeutic regimen. The duration of a particular therapeutic regimen may vary from one-time dosing to a regimen that extends for months or years.
Instant claim 47 requires that the patient’s hemoglobin level remains essentially unchanged during the period of maintenance. A person of ordinary skill treating patients would have been motivated to optimize dosing to minimize unwanted side effects such as changes in hemoglobin level.
Regarding instant claims 43-44 and 46, the prior art discloses methods of treatment comprising administering the LSD1 inhibitor in combination with at least one additional agent for the treatment of said disorder that is known in the art (paragraph [0175]). Rienhoff suggests additional agents such as the cytoreductive agent hydroxyurea (paragraph [0174]).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Rienhoff teaches methods of treating myeloproliferative neoplasms in a subject in need thereof, and for effecting specific clinically relevant endpoints in subjects by administering an LSD1 inhibitor but do not specify that the method is for maintaining leukocyte levels within a therapeutically beneficial range. The instant claims are generic to administering the LSD1 inhibitor of claim 38 at an unspecified therapeutic dose where maintenance of a desired leukocyte level is another advantage which would flow naturally from following the suggestion of the prior art. However, the prior art does not suggest maintaining the leukocyte count by periodically assessing a platelet count in the subject and adjusting the dose accordingly.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Carobbio et al. discuss “[t]hrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia” and report (abstract):
We found that a platelet count at diagnosis greater than 1000 × 109/L was associated with significantly lower rate of thrombosis in multivariable analysis and, if combined with leukocytes less than 11 × 109/L, pointed to a “low-risk” category with a rate of thrombosis of 1.59% of patients/year. On the contrary, the highest risk category (thrombosis rate, 2.95% of patients/year) was constituted of patients with leukocytosis, lower platelet count, and a JAK2V617F mutated genotype in most cases (77% vs 26% in the low-risk group), independently from standard risk factors.
Carobbio et al. suggest that prognostic risk of thrombosis is driven by a patient’s combination of white blood cell and platelet count. Accordingly, a person of ordinary skill performing the method of treating a myeloproliferative neoplasm, such as essential thrombocythemia to maintain a leukocyte count within a therapeutically beneficial range as disclosed by Rienhoff would have been motivated to monitor platelet count in the subject and adjust the treatment dosage to minimize the risk of thrombosis and optimize therapeutic outcomes as required by instant claim 38.
Regarding the limitations of instant claims 38 and 40 which require periodically assessing platelet count and adjusting the dosage as frequently as monthly or biweekly, Rienhoff teaches a dosing frequency of once a week. A person of ordinary skill treating a subject to maintain a suitable balance of platelets and leukocytes would have been motivated to reassess various risk factors such as platelet count and adjust the dose appropriately prior to weekly re-administration to optimize treatment.
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 38, 40, 43-44 and 46-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10519118 in view of WO2017079753A1 by Rienhoff and Carobbio et al. Blood (2008) 112 (8): 3135–3137.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patents disclose methods of treating KDM1A-mediated diseases by administering pharmaceutical salts of following compound:
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Lysine-Specific Histone Demethylase (LSD1) is also known as KDM1A therefore a person of ordinary skill would have been motivated to apply the method of the patents to treat LSD1 mediated myeloproliferative neoplasms by maintaining a leukocyte count within a therapeutically beneficial range which is the basis of subject matter rendered obvious relative to claims 38, 40, 43-44 and 46-47. The teachings of Rienhoff and Carobbio et al. relative to claims 38, 40, 43-44 and 46-47 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of patent No. 10519118 for the same reasons as under 35 USC 103.
Claims 38, 40, 43-44 and 46-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11230534 in view of WO2017079753A1 by Rienhoff and Carobbio et al. Blood (2008) 112 (8): 3135–3137.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patents disclose methods of treating KDM1A-mediated diseases by administering a genus of compounds that embrace the following LSD1 inhibitor of Rienhoff:
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Lysine-Specific Histone Demethylase (LSD1) is also known as KDM1A therefore a person of ordinary skill would have been motivated to apply the method of the patents to treat LSD1 mediated myeloproliferative neoplasms by maintaining a leukocyte count within a therapeutically beneficial range which is the basis of subject matter rendered obvious relative to claims 38, 40, 43-44 and 46-47. The teachings of Rienhoff and Carobbio et al. relative to claims 38, 40, 43-44 and 46-47 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of patent No. 11230534 for the same reasons as under 35 USC 103.
Claims 38, 40, 43-44 and 46-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11655226 and claims 1-58 of U.S. Patent No. 9790195 in view of WO2017079753A1 by Rienhoff and Carobbio et al. Blood (2008) 112 (8): 3135–3137.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patents disclose a genus of compounds that embrace the following LSD1 inhibitor of Rienhoff which is identical to the LSD1 inhibitor of instant claim 1:
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A person of ordinary skill would have been motivated to apply the compound of the patent to treat LSD1 mediated myeloproliferative neoplasms by maintaining a leukocyte count within a therapeutically beneficial range which is the basis of subject matter rendered obvious relative to claims 38, 40, 43-44 and 46-47. The teachings of Rienhoff and Carobbio et al. relative to claims 38, 40, 43-44 and 46-47 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of patent Nos. 11655226 and 9790195 for the same reasons as under 35 USC 103.
Claims 38, 40, 43-44 and 46-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 9981922 in view of WO2017079753A1 by Rienhoff and Carobbio et al. Blood (2008) 112 (8): 3135–3137.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 5 of the patent discloses the LSD1 inhibitor, N-[(2S)-5-{[(1R, 2S)-2-(4-fluorophenyl)cyclopropyl]amino}-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-yl]-4-(1H-1,2,3-triazol-1-yl)benzamide ditosylate which is identical to the LSD1 inhibitor of instant claim 1. A person of ordinary skill would have been motivated to apply the compound of the patent to treat LSD1 mediated myeloproliferative neoplasms by maintaining a leukocyte count within a therapeutically beneficial range which is the basis of subject matter rendered obvious relative to claims 38, 40, 43-44 and 46-47. The teachings of Rienhoff and Carobbio et al. relative to claims 38, 40, 43-44 and 46-47 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of patent No. 9981922 for the same reasons as under 35 USC 103.
Claims 38, 40, 43-44 and 46-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9-13, 16-25, 27, 31-53 and 55 of copending Application No. 17805130 in view of WO2017079753A1 by Rienhoff and Carobbio et al. Blood (2008) 112 (8): 3135–3137.
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 and 41 of the copending application disclose a method of treating essential thrombocythemia (ET) in a subject by administering the following compound in an amount sufficient to maintain a particular platelet count:
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The instant claims are generic to administering the LSD1 inhibitor of claim 1 at an unspecified therapeutic dose where maintenance of a desired leukocyte level is another advantage which would flow naturally from following the suggestion of copending claim 1. Rienhoff discloses methods of treating ET in a subject in need thereof, and for effecting specific clinically relevant endpoints in subjects by administering the copending LSD1 inhibitor. Carobbio et al. provide a motivation to consider platelet counts and leukocyte counts when treating patients with ET to minimize the prognostic risk of thrombosis. A person of ordinary skill would have been motivated to administer the compound of the copending claims to treat ET by maintaining a leukocyte count within a therapeutically beneficial range and additionally considering platelet count which is the basis of subject matter rendered obvious relative to claims 38, 40, 43-44 and 46-47. The teachings of Rienhoff and Carobbio et al. relative to claims 38, 40, 43-44 and 46-47 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of copending claims for the same reasons as under 35 USC 103.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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.
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/A.A.C./Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626