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 .
Priority
This Application filed on 03/31/2025 is a continuation of U.S. Application No. 19/114,480, filed on 03/24/2025, which is a National Stage of International Application PCT/JP2024/038683, filed on 10/30/2024, which claims the benefits of priority to U.S. Provisional Applications No. 63/594,442, filed on 10/31/2023, No. 63/604,527, filed on 11/30/2023, No. 63/645,182, filed on 05/10/2024, No. 63/658,920, filed on 06/12/2024, and No. 63/709,204, filed on 10/18/2024.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 10/23/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
DETAILED ACTION
Applicant’s amendment and arguments filed on 10/23/2025 have been received and have been carefully considered. Claims 55-57,61-62, 65-83 were amended, claims 58-60, 63-64, and 84 were canceled, and claims 1-54 were previously canceled. Claims 55-57, 61-62, and 65-83 are pending.
Withdrawn Claim objections
Objection to claim 65 for reciting “he” instead of “The”, is withdrawn in view of applicant’s amendment to claim 65 filed on 10/23/2025.
Objection to claims 67-84 for reciting abbreviations instead of the actual terms, is withdrawn in view of applicant’s amendment to claim 67-83 filed on 10/23/2025 that recites the term at first instance in claim 67.
Withdrawn Rejections 35 U.S.C. 112(b)
Rejection of claims 55-84 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for reciting “an active ingredient comprising”, is withdrawn in view of applicant’s amendment to claim 55 filed on 10/23/2025 that amended claim 55 with “consisting of” in place of “comprising”.
Withdrawn Claim Rejections - 35 USC § 112 (a)
Rejection of claims 55-84 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating leukemia, does not reasonably provide enablement for the treatment and prevention of the claimed scope of every type of cancer, is withdrawn in view of applicant’s amendment to claim 55 filed on 10/23/2025 that amended the claim with “wherein the cancer is leukemia”.
Withdrawn Claim Rejections - 35 USC § 102
Rejection of claims 55-57, 63-69, and 83-84 under 35 U.S.C. 102(a)(1) as being anticipated by K. Eguchi, et al. (Blood 2021; 138 (Supplement 1): 3339, is withdrawn in view of applicant’s amendment to claim 55 filed on 10/23/2025 that amended the claim with “wherein one dose of the active ingredient is 200 mg or 300 mg converted to the free form”.
Rejection Maintained/Modified
Claim Rejections - 35 USC § 103
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 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.
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.
§ 103 Rejection over Kamioka
Claims 55, 56, 57, 61, 62, 65, 66, 67, 68, 69, 71, 73, 75, 77, 79, 81, and 83 are rejected under 35 U.S.C. 103 as being unpatentable over S. Kamioka et al. (US PG Pub 2022/0288072 A1, 09/15/2022, “Kamioka” cited in the PTO-892 dated 07/24/2025).
Kamioka teaches an optically active azabicyclo ring derivative useful as a medicament, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising it, or a medicament comprising the composition for treating or preventing conditions related to the binding between menin and MLL, and a method for using the medicament for treating cancer. [Pg. 1, [0002], [0005]].
Kamioka teaches A method for treating a tumor comprising administrating the compound of formula (I), wherein the tumor is involved in Menin-MLL, [Pg. 12, [0337], [0338]]:
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wherein R1-4, R5A-5B, R6A-6D, U, Y, Z, X, a-d, and p are defined [Pg. 2].
Kamioka teaches species of compound (I) including 5-fluoro-2-[(4-{7-[(1S,3S,4R)-5-methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2-yl}pyrimidin-5-yl)oxy]-N,N-di(propan-2-yl)benzamide (Example 6), [Pg. 10, [0285], Pg. 59, [0905]]:
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Kamioka teaches that the above compound is used in a method of treating tumor, wherein the tumor is acute leukemia (including MLL acute leukemia, MLL partial tandem duplicate acute leukemia, NPM mutated acute leukemia, MOZ acute leukemia, NUP98 acute leukemia, and CALM acute leukemia), chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, polycythemia vera, malignant lymphoma (including B-cell lymphoma), myeloma (including multiple myeloma), etc. [Pg. 12, [0330]]. Kamioka teaches that the tumor is accompanied by high expression of HOXa gene cluster, or MEIS gene cluster. [Pg. 12, [0335]].
In view of the foregoing discussion, Kamioka teaches a method of treating MLL leukemia comprising administering species of compound of formula (I). Kamioka only differs from the instant claim 55 to the extent that one of ordinary skill in the art would have to specifically select the compound of Example 6 above from the list of formula (I) species.
However, Kamioka provides motivation to one of ordinary skill in the art to specifically select compound 6 for the treatment of cancer because Kamioka provides many biological test and studies that showed that effectiveness of compound of Example 6 above:
Kamioka teaches a test for evaluating the Inhibition of the Menin – MLL binding, wherein compounds of Example 3, 6, 7, and 10 are the most effective with an IC50 of less than 3.0 nM. [Pg. 60, [0913]- [0916]].
Kamioka teaches a test for evaluating the inhibition of cell proliferation, wherein compounds of Example 1, 5, 6, 7, 10, 11, 15 and 19 are the most effective with an IC50 (RS4) of between ˂0.01 and 0.02 nM, and compounds of Example 1, 3, 5, 6, 7, 10, 11, 15 and 19 are the most effective with an IC50 (MOLM-13) of between ˂0.01 and 0.03 nM. [Pg. 61, [0917]- [0920]].
Kamioka teaches a test for the inhibition of mRNA transcription with test compounds in MEIS1 and HOXA9 wherein compounds of Examples 1, 3, 4, 5, 6, 7, 8, 9, 10, and 11 showed the mRNA transcription inhibition activity which is caused by the binding inhibition of Menin and a MLL fusion protein. [Pg. 61, [0921]- [0923]].
Kamioka teaches a test for the hERG inhibition, wherein the results showed that there is a more than 1000 - fold excellent gap between the concentration at which 50 % of the proliferation of RS4; 11 cells were inhibited and the concentration at which 50 % of the hERG current was inhibited in the compounds of Examples 6, 7, 15, 16, and 18. [Pg. 62, [0924]- [0926]].
In view of Kamioka’s testing results, set forth above, it appears that compounds of Example 6 and 7 are the most effective compounds of the species of formula (I), (note the structure similarity between 6 and 7):
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Thus, it would have been prima facie obvious prior to the effective filing date of instantly claimed invention to select compound of Example 6 (or 7) for the treatment of acute leukemia by administering the compound orally to a subject with acute leukemia.
With regard to claim 55 amendment “wherein one dose of the active ingredient is 200 mg or 300 mg converted to the free form”, one of ordinary skill in the art would have been motivated with reasonable expectation of success to administer compound of Example 6 once or twice in a dose of 200 mg or 300 mg because Kamioka teaches that the compound is administered in one or several times in a concentration of 0.01 mg-300 mg, and the dose depends on administration method, the condition or age of patients, and the like. As guided by MPEP 2144.05, 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). "[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). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Therefore, Kamioka meet each and every limitation of claims 55, 61, and 62.
With regard to claims 56, and 57, Kamioka teaches that the administration route of the compound of formula (I) is oral, parenteral, intrarectal, or ophthalmic administration, and the daily dose depends on the type of compounds, administration methods, the condition or age of patients, and the like. For example, in the case of oral administration, the compound is administrated in one to several portions. [0704].
With regard to claims 65, 66, 67, 68, 69, and 83, Kamioka teaches that the above compound, e.g., compound of Example 6, is used in a method of treating tumor, wherein the tumor is acute leukemia (including MLL acute leukemia, MLL partial tandem duplicate acute leukemia, NPM mutated acute leukemia, MOZ acute leukemia, NUP98 acute leukemia, and CALM acute leukemia), chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, polycythemia vera, malignant lymphoma (including B-cell lymphoma), myeloma (including multiple myeloma), etc. [Pg. 12, [0330]]. Kamioka teaches that the tumor is accompanied by high expression of HOXa gene cluster, or MEIS gene cluster, or p53 gain-of-function mutation. [Pg. 12, [0335], [0336]]. Claims 71, 73, 75, 77, 79, and 81 are also met because administering 200 or 300 mg is established above.
Response to Argument
Applicant argues:
The efficacy, safety, pharmacokinetics, etc. of the claimed compound at various doses is fully verified in the present specification. In addition, the effectiveness of the 200 mg and 300 mg doses is also supported by the results of a Phase I/II clinical trial of DSP-5336, an internal name for the compound recited in the claims. The results have been published through New Releases of Sumitomo Pharma (December 9, 2024, (Submitted herewith as Exhibit A and in IDS filed herewith). An ASH literature (2024) accompanying the released information provides additional relevant information (submitted herewith as Exhibit B and in IDS filed herewith). As reported, DSP-5336 was administered to 84 relapsed/refractory AML patients with NPMI mutation (NPMlm)/MLL rearrangement (KMT2Ar), who were heavily pretreated. In KMT2Ar patients, administration of 300 mg twice daily resulted in an objective response rate (ORR) of 73.3% (11/15 cases) and a complete remission (CR/CRh) rate of 40% (6/15 cases). In NPM Im patients, administration of 200 mg or 300 mg twice daily resulted in an ORR of 58.8% (10/17 cases) and a CR/CRh rate of 47.1% (8,17 cases). Furthermore, as of June 2024. no dose-limiting toxicities had been reported in 81 patients. In light of the above, while Kamioka describes the compound of the present invention, there is no description suggesting that the compound should be selected from among many other compounds and administered orally at 200 mg or 300 mg for the purpose of treating leukemia.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive for the following reasons. Applicant provided News Releases of Sumitomo Pharma and an Oral Abstracts of ASH Annual Meeting as evidence of criticality of the claimed does of 200 mg and 300 mg. The News Releases of Sumitomo Pharma is published by the Applicant of the instant claims. MPEP § 716.02(b) explains, the evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). "[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). The presented Sumitomo’s data to support criticality of the claimed doses stated that:
Enzomenib was administered twice daily in continuous 28-day study cycles at dose levels from 40 mg BID up to 300 mg BID. Also presented were clinical activity results from the dose optimization cohorts at the dose levels of 200 mg BID and 300 mg BID. In 23 patients with KMT2Ar, the Objective Response Rate (ORR} using ELN 2017 criteria was 65.2% (15/23) and the proportion to achieve CR+CRh was 30.4% (7/23). In the subset of patients with KMT2Ar to receive 300 mg BID (n = 15), the ORR was 73.3% (11/15) and CR+CRh was 40% (6/15). In the 17 total patients with NPM1 mutation (NPM1im) who received 200 mg BID or 300 mg BID, the ORR was 58.8% (10/17) and the proportion to achieve CR+CRh was 47.1% (8/17}. The 400 mg BID dose optimization cohort is ongoing, with 21 patients enrolled as of the clinical cut-off and data planned for presentation at a future conference.
This provided data is not sufficient to support the criticality of the claimed doses for the following reasons: The data showed that administered doses are 40-300 mg without explicitly stating that doses 200 and 300 found to provide unexpected results. As provided in MPEP 716 (d), “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." However, the data stated that the doses are twice a day, whereas the claim does not recite the dose frequency and dose interval.
The data stated that the Objective Response Rate (ORR} was 65.2% (15/23) and the proportion to achieve CR+CRh was 30.4% (7/23) without providing the doses that produces these results. The provided data further stated that with 300 mg BID (n = 15), the ORR was 73.3% (11/15) and CR+CRh was 40% (6/15). Thus, these results are incomplete and are insufficient to support the criticality of the 300 mg dose. Note that the data does not explain how 73.3% is significant over 65.2%.
The data does not show criticality based on comparison with other doses, however, the data stated that 400 mg dose optimization is ongoing. Thus, without having the complete data, one cannot consider the results of 300 mg dose significant. ASH Annual Meeting does not provide criticality for 200 mg or 300 mg doses because the Abstract stated that a wide therapeutic range of 140 to 300 mg was observed. Therefore, while Applicant asserted that 200 mg and 300 mg provide unexpected results, it is still stand that the claims are obvious over Kamioka for the above reasons.
§ 103 Rejection over Burrows in view of Eguchi
Claims 55-57, 61-62, 65-83 are rejected under 35 U.S.C. 103 as being unpatentable over F. Burrows et al. (WO 2022/086986 A1, 04/28/2022, “Burrows” cited in the PTO-892 dated 07/24/2025) in view of K. Eguchi, et al. (Blood 2021; 138 (Supplement 1): 3339, “Eguchi” cited in the PTO-892 dated 07/24/2025).
Burrows teaches a method for treating hematological malignancies, using a menin inhibitor, wherein the hematological malignancy is acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or mixed phenotype acute leukemia (MP AL), [0013], wherein the methods are useful for treating diseases dependent on the activity of menin, MLL. The menin inhibitor can inhibit the protein-protein interaction of menin with an MLL protein, [0006], wherein in some embodiments, the menin inhibitor is a compound of Formula (VIIIа), R1-4, a-d, and p are defined, [Pg. 27-29, [0046]]:
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Burrows teaches species of Formula (VIIIa), for example, compound IX-6, [Pg. 203, Table 9b]:
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Burrows teaches that in some embodiments, the subject exhibits an overexpression or increased activity of MEIS1 protein, and overexpression or increased activity of H0XA9 protein. [0013]
Burrows teaches that a mutation in nucleophosmin (NMP) gene, a rearranged mixed-lineage leukemia (MLL-r) gene, or a combination thereof are identified in a tissue sample or cell of the subject with the hematological malignancy. [0016]. Burrows teaches that in some embodiments, the subject exhibits a mixed-lineage leukemia-partial tandem duplication (MLL-PTD). In some embodiments, a mutation in NPM1 gene, a rearranged mixed-lineage leukemia (MLL-r) gene, or a combination thereof, has been identified in a tissue sample or cell of the subject. [00299-00300]. Burrows teaches that hematological malignancy is relapsed and/or refractory acute myeloid leukemia (AML). [00292].
In view of the foregoing discussion, Burrows teaches a method of treating mixed-lineage leukemia (MLL), comprising administering species of compound of formula (I). Burrows only differs from the instant claim 55 to the extent that one of ordinary skill in the art would have to specifically select compound of IX-6 above from the list of Formula (VIIIa) species.
Eguchi teaches the use of DSP-5336, a novel, potent, and orally bioavailable MENIN-MLL interaction inhibitor for the treatment of acute leukemia patients with MLL-r or NPM1 mutation. [Abstract]. DSP-5336 with the chemical structure bellow, is the same claimed compound:
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Eguchi teaches that DSP-5336 directly bound to the MENIN protein (Kd = 6.0 nM) and inhibited the MENIN-MLL interaction (IC 50 = 1.4 ± 0.058 nM). DSP-5336 selectively inhibited the cell growth of human leukemia cell lines including MV-4-11, MOLM-13, KOPN-8, and OCI-AML3 (IC 50 = 10, 15, 31 and 15 nM, respectively). These DSP-5336-sensitive cell lines possess an MLL-r or NPM1 mutation. Eguchi teaches that that DSP-5336 exhibited a significant antitumor activity at the doses of 25 mg/kg and 50 mg/kg, administered twice daily (BID) for 20 days. DSP-5336 induced a significant prolongation of survival at the doses of 200 mg/kg once daily (QD).
Eguchi teaches that DSP-5336 significantly reduced the gene expression of MEIS1 and HOXA9, representative leukemic genes.
Eguchi teaches that DSP-5336 has a potential as an antitumor drug that provides survival advantages in acute leukemia patients with MLL rearrangement or NPM1 mutation. [Abstract]
It would have been prima facie obvious prior to the effective filing date of instantly claimed invention to select compound of IX-6 from Burrows’s list of menin inhibitors in view of the teachings of Eguchi. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Eguchi teaches that DSP-5336 exhibited significant antitumor activity, DSP-5336 has potential as an antitumor drug that provides survival advantages in acute leukemia patients with MLL rearrangement or NPM1 mutation, DSP-5336 strongly inhibited blast colony formation and changed the gene expression of the pharmacodynamics markers (HOXA9, MEIS1 and ITGAM), and DSP-5336 also induced a significant prolongation of survival compared to the vehicle control.
With regard to the claim 55 amendment “wherein one dose of the active ingredient is 200 mg or 300 mg converted to the free form”, Burrows teaches that compounds of Formula (VIIIa) are effective over a wide dosage range. For example, in the treatment of adult humans, dosages from 0.01 to 1000 mg per day, from 0.5 to 100 mg per day, from 1 to 50 mg per day, and from 5 to 40 mg per day are examples of dosages that may be used in some embodiments. The exact dosage will depend upon the route of administration, the form in which the compound is administered, the subject to be treated, the body weight of the subject to be treated, and the preference and experience of the attending physician. [Pg. 262, [00250]]. One of ordinary skill in the art would have been motivated to administer compound IX-6 (DSP-5336) in a dose of 200 mg or 300 mg in view of the teachings of Burrows. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Burrows teaches that the compound is administered at a range of 0.01-1000 mg. As guided by MPEP 2144.05, 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). "[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). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Therefore, Burrows in view of Eguchi meet each and every limitation of claims 55, 61, 62.
With regard to claims 56 and 57, Burrows teaches the compounds of Formula (VIIIa) are administered orally or intraperitoneal injection in an appropriate amount and frequency at the dosage indicated (e.g., 50 mg/kg, bid (twice a day); 50 gm/kg, qd (once a day); 100 mg/kg, bid; 100 mg/kg, qd; 200 mg/kg, qd.; or 200 mg/kg, bid). [Pg. 305-306, [00398]]. Eguchi also teaches that DSP-5336 is administered once or twice a day. [Abstract].
With regard to claims 65, 66, 67, 68, 69, 70, 72, 76, 78, 82, and 83, Burrows teaches that the hematological malignancy may be acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or mixed phenotype acute leukemia (MPAL). Burrows teaches that in some embodiments, the subject exhibits an overexpression or increased activity of MEIS1 protein, and overexpression or increased activity of H0XA9 protein. [Pg. 3, [0013]]. Burrows teaches that the hematological malignancy subject has a mutation in nucleophosmin (NMP) gene, a rearranged mixed-lineage leukemia (MLL-r) gene, a mutation in NPM1 gene, a mixed-lineage leukemia-partial tandem duplication (MLL-PTD), or a combination thereof. [[Pg. 4, [0016], pg. 276, [00299], pg. 277, [00300]]. Burrows teaches that hematological malignancy is relapsed and/or refractory acute myeloid leukemia (AML). [Pg. 273, [00292]]. Claims 71, 73, 75, 77, 79, and 81 are also met because administering 200 or 300 mg is established above.
With regard to claims 74, 80 directed to relapsed or refractory acute lymphoid leukemia, Burrows teaches that the hematological malignancy may be acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL). [Pg. 3, [0013]]. Burrows teaches that the mixed-lineage leukemia (MLL) protein is a histone methyltransferase critical for the epigenetic regulation of gene transcription. Many acute leukemias, including acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) and mixed-lineage leukemia (MLL), are characterized by the presence of chimeric MLL fusion proteins that result from chromosomal translocations of the MLL gene. [Pg. 1, [0002]]. Burrows teaches that the hematological malignancy is acute myeloid leukemia (AML) (e.g., relapsed and/or refractory AML), acute lymphocytic leukemia (ALL), or mixed phenotype acute leukemia (MPAL). [Pg. 273, [00292]]. In view of the foregoing, one of ordinary skill in the art would have been motivated to use compound DSP-5336 in the treatment of relapsed or refractory acute lymphoid leukemia.
Response to Arguments
Applicant argues:
Burrows disclose formulas that encompass the present compound in the context of a vast disclosure of alternative compounds and without providing any indication or suggestion that the present compound has unique properties or any other basis to select it. Eguchi provides certain information relating to certain data derived from use of DSP-5336. However, Eguchi does not describe the structure of DSP-5336. Moreover, nothing in Eguchi or any other prior art provided a person of skill in the art with any indication or suggestion of what DSP-5336 is or how to make it. In the absence of any indication in Eguchi of what compound is administered a skilled artisan had no reason to turn to Burrows to find DSP-5336.
Examiner response:
Applicant’s argument with respect to DSP-5336 is unclear. Applicant appears to inquire about the well-known compound DSP-5336, which is also known as Enzomenib by questioning “what DSP-5336 is or how to make it?”. Examiner attached herewith an evidentiary document for DSP-5336 form NIH, PubChem: 06/27/2020, https://pubchem.ncbi.nlm.nih.gov/compound/Enzomenib. Eguchi discloses “Preclinical Evaluation of a Novel Orally Bioavailable Menin-MLL Interaction Inhibitor, DSP-5336, for the Treatment of Acute Leukemia Patients with MLL-Rearrangement or NPM1 Mutation” Title. Thus, Applicant's arguments have been fully considered but they are not persuasive.
Applicant argues:
In addition, the present claims recite a method of administering a dosage of DSP-5336 of 200 mg or 300 mg orally to a human. In contrast, Eguchi reports on administering 25, 50, and 100 mg/kg of DSP-5336 to a mouse. Those doses are all at least five times as high as the doses recited in the amended claims. There is no reason of record that would have led a skilled artisan to attempt to do so. And then, even if a skilled artisan had for an unknown reason decided to select DSP-5336 and administer it to a human, the evidence of record provided no basis whatsoever for the skilled artisan to have expected success.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive for the following reasons. Applicant argues that Eguchi administered the claimed compound to mice, whereas the instant claims are drawn to a method of administering a dosage of DSP-5336 to a human. However, the instant claims are directed to a method for treating a cancer comprising” orally administering, to a subject in need thereof, …”. The instant specification describes the term “subject” as: “in some embodiments, the subject treated by the above methods is a mammal. The present compound can be used to mammals, and the term "mammal" is used herein in its normal biological meaning. Accordingly, it includes, for example, humans, cows, horses, dogs, cats, rats, mice, but also many other species. In some further embodiments, the subject is a human.” [0186]. Applicant’s argument that the dose of Eguchi is higher than the claimed doses, is not persuasive when the teachings of Eguchi is combined with Burrows. One of ordinary skill in the art would have been motivated to administer compound IX-6 (DSP-5336) in a dose of 200 mg or 300 mg because Burrows teaches that compound is effective over a wide dosage range, e.g., in the treatment of adult humans, dosages from 0.01 to 1000 mg per day, and from 0.5 to 100 mg per day, and the exact dosage will depend upon the route of administration, the form in which the compound is administered, the subject to be treated, the body weight of the subject to be treated, and the preference and experience of the attending physician. [Pg. 262, [00250]]. As guided by MPEP 2144.05, 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). "[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). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
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 55-57, 61-62, 65-69, 71, 73, 75, 77, 79, 81, and 83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of US Patent No. 11,369,605 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims recite a method for treating a cancer, comprising: orally administrating, to a subject in need thereof, a therapeutically effective amount of an active ingredient consisting of 5-fluoro-2-[(4-{ 7-[(1 S,3S,4R)-5- methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2- yl}pyrimidin-5-yl)oxy]-N,N-di(propan-2-yl)benzamide in free form or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, wherein one dose of the active ingredient is 200 mg or 300 mg converted to the free form, and wherein the cancer is leukemia, wherein the acute leukemia is MLL acute leukemia or NPM1 mutated acute leukemia, acute myeloid leukemia with MLL rearrangement, acute lymphoid leukemia with MLL rearrangement, acute myeloid leukemia with NPM1 mutation, or leukemia accompanied by high expression of HOXa gene cluster or MEIS gene cluster.
US Patent No. 11,369,605 B2 recites in claims 1-39 a compound of formula (Ia), wherein the claimed compound, 5-Fluoro-2-[(4-{7-[(1S,3S,4R)-5-methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2-yl}pyrimidin-5-yl)oxy]-N,N-di(propan-2-yl)benzamide, recited in claim 34 as one of formula (Ia) species, wherein the compound used in a method for treating a tumor comprising administrating the compound or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the tumor is involved in Menin-MLL. US Patent No. 11,369,605 B2 does not recite the types of cancer or the dosing amounts.
However, MPEP 804 states: The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
With regard to claims 56, 57, 61, 62, US Patent No. 11,369,605 B2 teaches that the compound of formula (I) can be administered orally, and the daily dose depends on the type of compounds, administration methods, the condition or age of patients, and the like. [Col. 53, ln. 41-45]. For example, in the case of oral administration, about 0.01 to 1000 mg, more preferably about 0.1 to 500 mg per kg body weight of a human or mammal can be usually administrated in one to several portions, in about 0.01 mg to 300 mg, more preferably about 1 mg to 100 mg per kg body weight of a human or mammal. [Col. 53, ln. 45-52]. One of ordinary skill in the art would have been motivated to administer compound of Example 6 once or twice in a dose of 200 mg or 300 mg because US Patent No. 11,369,605 B2 teaches that the compound is administered in one or several times in a concentration of 0.01 mg-300 mg, depends on administration method, the condition or age of patients, and the like. As guided by MPEP 2144.05, 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). "[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). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to claims 65, 66, 67, 68, 69, and 83, US Patent No. 11,369,605 B2 teaches that the menin inhibitor i.e., 5-fluoro-2-[(4-{7-[(1S,3S,4R)-5-methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2-yl}pyrimidin-5-yl)oxy]-N,N-di(propan-2-yl)benzamide, is used in a method of treating tumor, wherein the tumor is acute leukemia (including MLL acute leukemia, MLL partial tandem duplicate acute leukemia, NPM mutated acute leukemia, MOZ acute leukemia, NUP98 acute leukemia, and CALM acute leukemia), chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, polycythemia vera, malignant lymphoma (including B-cell lymphoma), myeloma (including multiple myeloma), etc. [Col. 20, ln. 49-67]. US Patent No. 11911381B2 teaches that the tumor is accompanied by high expression of HOXa gene cluster, or MEIS gene cluster, or p53 gain-of-function mutation. [Col. 27, ln. 53-59]. Claims 71, 73, 75, 77, 79, and 81 are also met because administering 200 or 300 mg is established above.
Claims 55-57, 61-62, 65-83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 11, 16, 28-40 of Copending Application No. 19/114,480. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims recite a method for treating a cancer, comprising: orally administrating, to a subject in need thereof, a therapeutically effective amount of an active ingredient consisting of 5-fluoro-2-[(4-{7-[(1S,3S,4R)-5-methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2- yl}pyrimidin-5-yl)oxy]-N,N-di(propan-2-yl)benzamide in free form or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, wherein one dose of the active ingredient is 200 mg or 300 mg converted to the free form, and wherein the cancer is leukemia, wherein the acute leukemia is MLL acute leukemia or NPM1 mutated acute leukemia, acute myeloid leukemia with MLL rearrangement, acute lymphoid leukemia with MLL rearrangement, acute myeloid leukemia with NPM1 mutation, or leukemia accompanied by high expression of HOXa gene cluster or MEIS gene cluster.
Copending Application No. 19/114,480 recites in claim 1 a medicament comprising 5-fluoro-2-[(4- {7-[(1S,3S,4R)-5- methylidene-2-azabicyclo[2.2.2] octane-3-carbonyl]-2,7-diazaspiro[3.5] nonan-2-yl} pyrimidin-5-yl)oxy] -N,N- di(propan-2-yl)benzamide or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof as an active ingredient, for treating or preventing a cancer, which is orally administered to a subject in need thereof. Dependent claims of Copending Application No. 19/114,480 recite “wherein the medicament administered once or twice a day, one dose of the active ingredient is 200 mg or 300 mg converted to the free form, and wherein the cancer is leukemia, wherein the acute leukemia is MLL acute leukemia or NPM1 mutated acute leukemia, acute myeloid leukemia with MLL rearrangement, acute lymphoid leukemia with MLL rearrangement, acute myeloid leukemia with NPM1 mutation, or leukemia accompanied by high expression of HOXa gene cluster or MEIS gene cluster. Therefore, combination of claims 1-3, 11, 16, 28-40 of copending Application No. 19/114,480 meets the limitation of the instant claims 55-57, 61-62, 65-83.
Response to Arguments
Applicant argues:
The claims are amended and thus this rejection is moot. Applicant respectfully submits that the rejection should be reconsidered and withdrawn.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive because US Patent No. 11,911,381 B2 still reads on the amended claims. See the above Non-statutory double patenting rejection.
Conclusion
Claims 55-57, 61-62, 65-83 are rejected. No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622