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
The instant application, filed 11/19/2024, is the national stage entry of PCT/US2023/023202, filed 05/23/2023, which claims priority to U.S. Provisional Patent Application No. 63/344,803, filed on 05/23/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR § 1.55. However, see Assessment of Effective Filing Date section below.
Information Disclosure Statement
The four Information Disclosure Statement received of record are acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. One reference struck from the 7 page IDS received 02/21/2025 for lack of a translation. Accordingly, the Information Disclosure Statements have been considered.
Status of Claims
Claims 1-34 were originally presented on 11/19/2024. Applicant’s preliminary amendments to the claims received on 05/20/2025 are acknowledged and entered. Applicant states:
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Preliminary Amendments received on 05/20/2025 at 21.
Accordingly, claims 1, 4-8, 11-13, 18-23, 26-28, 31, and 34 are pending.
Claim Objections
Claims 1, 4-8, 11-13, 18-23, 26-28, 31, and 34 objected to because of the following informalities:
The preliminary amendments to the claims received on 05/20/2025 do not comply with 37 CFR § 1.121. See 37 CFR § 1.121(c)(1), which states in part:
The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
37 CFR § 1.121(c)(1) (emphasis added).
The preliminary amendments do not comply with the rule because the claim listing contains the text of other parts of the amendment (the Remarks). See Preliminary Amendments received on 05/20/2025 at 2, Remarks preceding claim 1:
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…
Preliminary Amendments received on 05/20/2025 at 2.
The Remarks preceding claim 1 are improper on the same sheet of paper. Further, they are duplicative of the Remarks section on page 21. When presenting claim amendments, Applicant is required to comply with the “Manner of making amendments in applications” as set forth in 37 CFR § 1.121. Failure to comply with the rule will result in delays in processing.
Appropriate correction is required.
Assessment of Effective Filing Date
The examiner finds that the effective filing date of the claimed invention is the filing date of PCT/US2023/023202, filed 05/23/2023. Applicant’s priority document, U.S. Provisional Patent Application No. 63/344,803, filed on 05/23/2022, hereinafter “the ’803 application”, represents a prophetic disclosure of compounds I-1 – I-20 and II-1 – II-30. The compounds are drawn in the ’803 application at 37-50. Applicant speculates in the ’803 application at 51 that these compounds may be synthesized by “SCHEME 1”:
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The ’803 application at 51.
No evidence of actual possession of these compounds is demonstrated in the ’803 application. For example, Applicant presents no 1H NMR data for the prophetic compounds drawn in the ’803 application. Compare the ’803 application at entire document to Instant Specification at 70-71, presenting the synthesis and 1H NMR for compound I-1:
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Instant Specification at 70-71.
Because the compounds drawn in the ’803 application are prophetic, Applicant presents no biological data enabling their use. For example, while the Instant Specification at 83 provides the following data from an NSD2 inhibitory assay for the compounds I-1, I-6, and II-2, no such data is reported in the ’803 application:
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I-1
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I-6
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II-2
Biological data from the Instant Specification at 83, compounds from id. at 37, 38, and 42.
Accordingly, the examiner finds the effective filing date of the claimed invention is the filing date of the PCT, 05/23/2023. The PCT is where Applicant first demonstrates possession of the claimed invention and presents an enabling disclosure.
Claim Rejections - 35 USC § 102(a)(2)
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 person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 5, 6, 11, 12, 13, 18, 23, 27, 28, 31 and 34 Anticipated by WO’283 as evidenced by US’100
Claim(s) 1, 4, 5, 6, 11, 12, 13, 18, 23, 27, 28, 31 and 34 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO’283 as evidenced by US’100.1
The instant claims are drawn to methods of treating NSD2 diseases or conditions (e.g., cancers) comprising administering:
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wherein
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…
Ring A may be (note dashed box added by examiner):
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,
Such as
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.
WO’283 claims priority to U.S. Provisional Patent Application No. 63/377,100, hereinafter “US’100”, which was filed 2022-09-26. Reference will be made to the pages of US’100.
US’100 teaches methods of treating NSD2 diseases or conditions comprising administering multiple compounds of claim 1. See biological data from US’100 at 35, and compounds from pages 24 and 30-32:
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at 24,
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US’100 at 35, and compounds from pages 24 and 30-32.
See also, US’100 at 37-44, claims 1 and 34-41:
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US’100 at 37-44, claims 1 and 34-41.
The example compound 9 of US’100
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is a compound of instant claims 1 (R1 = H, R2 =
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, m, p, q=0, n=2, R6 = halo (F)), 4, 5, 12, 13, 18, and 23. US’100 teaching its administration for treating NSD2 diseases or conditions such as leukemia (US’100 at claim 38) as the compound, salt, or pharmaceutical composition forms, as well as in assays (Table 3 of US’100 at 35), anticipates claims 1, 4, 5, 12, 13, 18, 23, 27, 28, 31 and 34.
Accordingly, claims 1, 4, 5, 12, 13, 18, 23, 27, 28, 31 and 34 are anticipated by US’100.
Regarding claim 6, it recites:
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Claim 6.
The example compound 1 of US’100
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corresponds to a compound of claim 6 wherein R1 is
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.
If Applicant does not intend claim 6 to encompass the US’100 Example compound 1, it needs to amend the text of the claim so that it is clear what compounds are claimed for the R1 variables. The examiner reads claim 6 as stating wherein “R1 is C1-6 alkyl substituted with … halo … and hydroxyl, C1-6 alkoxy, C1-6 haloalkoxyl, O-(C3-5 cycloalkyl), oxo, -C(O)OR3,” as separate from “R1 is …, or -C(O)N(R4)2.”
Accordingly, claim 6 is anticipated by US’100.
Regarding claim 11, it recites:
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Claim 11.
The example compounds 5-8 of US’100
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correspond to a compound of claim 11 wherein m is 0.
Accordingly, claim 11 is anticipated by US’100.
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.
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.
Claims 1, 4, 5, 6, 7, 8, 11, 12, 13, 18, 23, 26, 27, 28, 31 and 34 were obvious over WO’283 as evidenced by US’100 in view of WO’854
Claim(s) 1, 4, 5, 6, 7, 8, 11, 12, 13, 18, 23, 26, 27, 28, 31 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO’283 as evidenced by US’1002 in view of WO’854.3
The rejections of claims 1, 4, 5, 6, 11, 12, 13, 18, 23, 27, 28, 31 and 34 under 35 U.S.C. 102(a)(2) as being anticipated by WO’283 as evidenced by US’100 are fully incorporated herein.
WO’283 as evidenced by US’100 does not expressly teach the administration of compounds of instant claim 1 wherein the piperidine portion
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is attached to R1 of
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such as the following compounds recited in claim 26:
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However, one of ordinary skill in the art at the time of filing would have a reasonable expectation of success in replacing the amide R1
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of US’100 example 4
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with a
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because WO’854 teaches preferrable attachments for the piperidine ring in its structural activity relationship study about NSD2 receptors.
WO’854
WO’854 at 215-220, claims 1, 7, 10, and 20-26 teach methods of treating diseases and conditions mediated by NSD2 comprising administering
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,
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wherein exemplary compounds include the following active pharmaceutical ingredients (“API”s):
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The diastereomers 160 and 161 of WO’854 represent preferrable attachments for piperidine ring. See, e.g., Table 2 of WO’854 at 183, which teaches a structural activity relationship study (a “SAR study”, or just a “SAR”) about NSD2 receptors.
See Table 2 Caption at 181,
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and Table 2 at 183-215, with data for compounds 160 and 161 at 199:
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The diastereomers 160 and 161 of WO’854 had an R1 of
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connected with (R) configuration to the piperidine and exhibited sub 0.01 μM activity in NSD2 inhibition assays, both of which were very good. Therefore, in its SAR study, WO’854 teaches a preferrable R1 of
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when preparing an API effective for treating diseases and conditions mediated by NSD2.
Accordingly, one of ordinary skill in the art at the time of filing would have a reasonable expectation of success in replacing the amide R1
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of US’100 example 4
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with a
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because WO’854 explained in its SAR study that such attachments were preferrable to select for the piperidine ring. Both compounds prepared in such a manner are compounds of the general formulas of US’100 as well as the instant claims. Further, both are recited in claim 26,
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Accordingly, claims 1, 4, 5, 6, 7, 8, 11, 12, 13, 18, 23, 26, 27, 28, 31 and 34 were obvious at the time of filing.
Claims 1, 4, 5, 6, 7, 8, 11, 12, 13, 18, 19, 20, 21, 22, 26, 27, 28, 31 and 34 were obvious over WO’854 in view of Patani 1996
Claim(s) 1, 4, 5, 6, 7, 8, 11, 12, 13, 18, 19, 20, 21, 22, 26, 27, 28, 31 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO’8544 in view of Patani 1996.5
WO’854 is relied upon as above.
The above claims encompass the following compounds, their diastereomers, and their use in treating diseases and conditions mediated by NSD2:
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As discussed, WO’854 teaches methods of treating diseases and conditions mediated by NSD2 comprising administering exemplary compounds including the following APIs:
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As discussed, the diastereomers 160 and 161 of WO’854 exhibited sub 0.01 μM activity in NSD2 inhibition assays, both of which were very good. As discussed, WO’854 teaches a SAR study about NSD2 receptors.
Applicant’s exemplified compounds are classical bioisosteres of the above diastereomers of WO’854. The only difference between the compounds is the classical bioisosteric exchange of CH for N. WO’854 suggests that one of ordinary skill in the art at the time of filing would have a reasonable expectation of success in administering the above compounds I-1, I-6, I-12, and I-17 in methods of treating diseases and conditions mediated by NSD2 because Patani 1996 teaches that there was a reasonable expectation that the classical bioisosteres would affect the same pharmacological targets in the same way and thereby have related properties.
Patani 1996
The exchange of the CH for N represents a classical bioisosteric exchange “according to Grimm”. See Patani 1996 at 3148, right column, Table 2, discussed below.
Patani 1996 has been cited thousands of times by numerous authors for its review of “Bioisosterism: A Rational Approach in Drug Design”. See Patani 1996 at Title. On the first page, it explains that “Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents.” Patani 1996 at 3147. The approach was considered “intuitive”, id., and had its roots back to 1919, id. at 3148. Bioisosteres are “Compounds or groups that possess near-equal molecular shapes and volumes, approximately the same distribution of electrons, and which exhibit similar physical properties...”. Id. “The critical component for bioisosterism is that bioisosteres affect the same pharmacological target as agonists or antagonists and, thereby, have biological properties which are related to each other.” Id.
“Bioisosteres have been classified as either classical or nonclassical.” Id. One such group of classical bioisosteres were those “according to Grimm”, see Patani 1996 at 3148, Table 2 and surrounding text (second column shows the CH for N exchange):
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Patani 1996 at 3148, Table 2.
See also, Patani 1996 at 3158, “E. Ring Equivalents” section, teaching simple of examples commonly employed in medicinal chemistry such as phenyl and pyridine swaps. See also, Patani 1996 at 3159-3160, “2. Trivalent Ring Equivalents” section, which expressly states at 3159 (“The trivalent substitution of –CH= with –N= is commonly used in modern drug design.”).
Compounds I-1, I-6, I-12, and I-17 were obvious at the time of filing
Accordingly, one of ordinary skill in the art at the time of filing would have a reasonable expectation of success in performing the trivalent substitution of –CH= with –N=, and vise versa, when modifying the central pyridine scaffold of the compounds of WO’854, such as its example 160 and 161 compounds, because there was a reasonable expectation that the resulting classical bioisosteres would affect the same pharmacological targets in the same way and thereby have related properties.
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Therefore, the person of ordinary skill in the art at the time of filing had a reasonable expectation that the following compounds would be effective in methods of treating diseases and conditions mediated by NSD2:
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It would take only ordinary and routine experimentation to determine effective amounts of each classical bioisostere to administer in the methods by following the assays taught explicitly in WO’854. WO’854 taught the indications for these compounds when administered either alone or in a pharmaceutical composition with one or more pharmaceutically acceptable carriers. See, e.g., WO’854 at 219-220, claims 18-26 (e.g., leukemias).
Accordingly, claims 1, 4, 5, 6, 7, 8, 11, 12, 13, 18, 19, 20, 21, 22, 26, 27, 28, 31 and 34 were obvious at the time of filing.
Prior Art Cited but not Applied
The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
U.S. Patent Application No. US 20240417401 A1. Presently unclear if this application is a Potential NSDP reference.
International Application No. WO 2021026803 A1. In family with WO’854.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christopher Evan Redwood whose telephone number is (571) 272-8882. The examiner can normally be reached Monday - Friday 6:15 AM - 4:45 PM.
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/C.E.R./ Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629
1 LE KANG, et al., “HETEROCYCLES AS MODULATORS OF NSD ACTIVITY”, International Publication No. WO 2024073283 A1, published 2024-04-04, filed 2023-09-20, priority to 2022-09-26, Board of Regents, The University of Texas System Applicant, hereinafter “WO’283”. WO’283 claims priority to U.S. Provisional Patent Application No. 63/377,100, hereinafter “US’100”, which is attached hereto and was made public with the publication of WO’283.
2 WO’283 and US’100 are the same reference(s) used in the section regarding anticipation.
3 DENG HAIBING, et al., “PIPERIDINYL-METHYL-PURINEAMINES AS NSD2 INHIBITORS AND ANTI-CANCER AGENTS”, International Publication No. WO 2021028854 A1, published 2021-02-18, NOVARTIS AG Applicant, hereinafter “WO’854”.
4 Same reference as in the preceding 103 rejection.
5 Patani, George A., and Edmond J. LaVoie. "Bioisosterism: a rational approach in drug design." Chemical reviews 96.8 (1996): 3147-3176, hereinafter “Patani 1996”.
Prosecution Insights