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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-15, drawn to a compound of Formula, and the following species:
compound 160 having the structure of:
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as the elected compound species of Formula (I); and
an anti-cancer agent as the elected therapeutically active agent,
are maintained.
Claims 16-19 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected species conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected compound species of Formula (I).
In light of this discovery, the search was expanded to the subject matter of the full scope of the compound of formula (I). The fact that the compound of Formula (I) is also recited in the combination, the comprehensive search of the therapeutically active agents was not burdensome to the Examiner. Therefore, the restriction requirement among the compound species of Formula (I) and the therapeutically active agent species, as set forth in the Office action mailed on March 5, 2025 is hereby withdrawn.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on August 29, 2025, wherein claims 1-2 and 5-14 are amended; claims 3-4 and 15-19 are unchanged; claim 20 is cancelled; and claim 21 is newly added.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-19 and 21 are pending. Claims 16-19 remain withdrawn.
Claims 1-15 and 21 are under examination in accordance with the elected species along with the expanded compound set forth in the Expansion of Species section above.
Priority
The instant application 17/761,902 filed on March 18, 2022 is a 371 of PCT/IB2020/058735 filed
on September 18, 2020, which claims priority to, and the benefits of Foreign Application No.
PCT/CN2019/107010 filed on September 20, 2019 and Foreign Application No. PCT/CN2020/095916 filed on June 12, 2020.
Action Summary
Applicant’s amendment to the claims have overcome each and every objection previously sets
forth in the Non-Final Office Action mailed on May 29, 2025.
Claims 2-4 and 12 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention are withdrawn in view of the claim amendments.
Claims 1-5, 7-8, 10-11 and 13-15 rejected under 35 U.S.C. 103 as being obvious over Deng et al. (WO 2021/026803 A1), in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) are withdrawn in view of the statement pursuant to 35 U.S.C. 102(b)(2)(C) in the reply filed on August 29, 2025. Applicant has provided a submission in this file that the claimed invention and the subject matter disclosed in the prior art reference were owned by, or subject to an obligation of assignment to, the same entity as Novartis AG not later than the effective filing date of the claimed invention.
Claims 1-5, 7-8, 10-11 and 13-15 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,420,970 B1 (referred to herein as ‘970 patent) in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) are maintained.
Claims 1-2, 10, and 13-15 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-41 of copending Application No. 17/739,855 (referred to herein as ‘855 application) in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) are maintained, but revisited and modified in view of the issued U.S. Patent No. 12,312,353 B2 published on May 27, 2025.
Claim Objections
Claim 21 is objected to because of the following informalities (newly applied as necessitated by amendment):
Regarding claim 21, the recitation of “halo,” and the recitation of “-haloC1-6alkyl” are missing a coordinating conjunction –or– in between to connect these two recitations. In addition, the recitation of “-haloC1-6alkyl” and the recitation of “provided at least two of R7, R8, R9 and R10 are not hydrogen” are also missing a coordinating conjunction –and—in between to connect the clauses.
Appropriate correction is required.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7-8, 10-11 and 13-15 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,420,970 B1 (referred to herein as ‘970 patent) in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176).
The claims of ‘970 patent is drawn to a compound of Formula (I) or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof useful for treating a disease or condition mediated by nuclear SET domain-containing protein 2, such as breast cancer; wherein said compound is selected from a compound in the following table, or a pharmaceutically acceptable salt thereof, inter alia,
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. The claims of ‘970 patent is also drawn to a pharmaceutical composition comprising the compound of Formula (I) or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carrier. Please note compound of Ex No. 85 of ’970 patent has a chemical structure of:
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(see e.g., p. 126, Example 85 of ‘970 patent).
The claims of ‘970 patent does not expressly teach a compound species of Formula (I) instantly claimed.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents (see e.g., “introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar biological activity, and have been classified as either classical or nonclassical, wherein the classical bioisosteres are a series of replacements defined by Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres (see e.g., p. 3148-3149). Patani et al. further teaches the use of the classical bioisosteres benzene and pyridine resulted in analogues with retention of biological activity within different series of pharmacological agents (see e.g., p. 3158, “E. Ring Equivalents” section). Patani et al. further teaches the trivalent substitution of -CH= with -N= is commonly used in modern drug design, for example, said substitution in the (benzothiazolylbenzyl)phosphonate derivatives retained vasodilatory activity as shown below:
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(see e.g., page 3159, right column, under “trivalent ring equivalent” to page 3160, left column, table 30). Patani et al. further teaches the replacement of hydrogen with hydroxyl also results analogues, for example, said substitution in N-[2-(Mercaptomethyl)-3-phenylbutanoyl] amino acids as shown below:
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resulting no significant alteration in preferential activity with either of the peptidases, ACE or NEP (see e.g., p. 3152, “4. Fluorine and Hydroxyl, Amino, or Methyl Groups as Replacements for Hydrogen (Grimm’s Hydride Displacement Law)” section, left column to right column, 1st paragraph).
In the present case, the difference between the compound 85 of ‘970 patent and the expanded compound species of instant Formula (I) lies on the pyridine ring attached to the piperidine moiety of the compound 85 of ‘970 patent as shown below (see shaded):
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to select the compound 85 of ‘970 patent, and then modify said compound by replacing the pyridine ring attached to the piperidine moiety with a benzene ring as taught by Patani et al. One would have been motivated to do so, because Patani et al. teaches the replacement of pyridine with benzene, which is a bioisosteric replacement technique based on Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres, can results in analogues with retention of biological activity. One would have a reasonable expectation of success, because one would have reasonably expected that modifying the pyridine ring of compound 85 of ‘970 patent with a benzene ring would have successfully arrive at a compound useful for treating a disease or condition mediated by nuclear SET domain-containing protein 2, and therefore the modified compound 85 of ‘970 patent in view of Patani et al. can successfully incorporate into a pharmaceutical composition and a combination without any appreciable loss of activity.
Please note the modified compound 85 of ‘970 patent in view of Patani et al., in this case, a compound having the structure of:
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, is a compound of Formula (I)
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, wherein A is N; R1 is H; n is 1; R2 is
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, and that meets the limitation of “R2 is … (iv) –(CRaRb)r-C(=O)-NR12R13-(CRaRb)s” (wherein R12 is hydrogen; R13 is a 5-membered monocyclic heterocyclic ring comprises 1 heteroatom selected from oxygen; r and s are independently 0); R3b, R3a, R4a, R4b, R5a, R5b, R6a and R6b are independently hydrogen; R7, R9 and R10 are independently hydrogen; R8 is phenyl, wherein said phenyl is independently substituted with 2 R20, wherein R20 is fluoro and that meets the limitation of “-halo”; and a compound of subgenus Formula (II)
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, wherein A is N; R2 is
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, and that meets the limitation of “R2 is … (ii) –(CRaRb)r-C(=O)-NR12R13” (wherein R12 is hydrogen; R13 is a 5-membered monocyclic heterocyclic ring comprises 1 heteroatom selected from oxygen; r is 0); R7, R9 and R10 are independently hydrogen; R8 is phenyl, wherein said phenyl is independently substituted with 2 R20, wherein R20 is fluoro and that meets the limitation of “-halo”.
With respect to “wherein said compound is a compound of Formula (III):
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” in claim 3 and “wherein said compound is a compound of Formula (IV):
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“ in claim 4, in the absence of showing unobvious results, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention when faced with ‘970 patent and Patani et al. et al to make the instantly claimed derivatives of a known compound. Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). In the present case, the structural difference between the modified 85 of ‘970 patent in view of Patani et al. as set forth above and the claimed compound of Formula (III) is that the prior art compound contains a pyridine ring (see shaded:
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) and the claimed compound of instant Formula (III) contains the pyrrolidine ring (see shaded:
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). The pyrrolidine ring of Formula (III) instantly claimed shares a similar chemical structure with the primary difference being the size of their respective rings, specifically, pyrrolidine is a 5-membered ring comprising 1 nitrogen atom while pyridine is a 6-membered ring comprising 1 nitrogen atom. Therefore, the claimed invention is prima facie obvious to one of the ordinary skilled in the art at the time the application was filed. One would have been motivated to prepare similar compounds that are pharmacologically active compounds useful for treating cancer, including breast cancer. The instant obviousness rejection is based on the close structural similarity of the instantly claimed compounds to the compounds of reference patent in view of Patani et al., and the common utility shared among the compounds. There is an expectation among those of ordinary skill in the art that similar structural compounds will have similar properties and that modification of a known structure is mere experimentation within the means of a skilled artisan. See MPEP 2144.09(I). Please note the fact that ‘970 patent teaches a enantiomeric mixture of compound 85, and therefore the modified compound 85 of ’970 patent in view of Patani et al. meets the limitation of
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recites in the claimed Formula (IV).
With respect to “wherein R2 is
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” in claim 5, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the compound 85 of ‘970 patent in view of Patani et al. as set forth above by replacing
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with
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at the R2 position of Formula (I) of ‘970 patent. One would have been motivated to do so, because ‘970 patent clearly teaches a list of suitable R2, including –(CRaRb)r-C(=O)-NR12R13 and -C(RaRb)p-C(=O)-OR10, that can arrive a compound of Formula (I) useful for treating NSD2 mediated disease or condition; and specifically teaches compound 78 (“
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”) that is a compound of Formula (I) containing
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at R2. One would have a reasonable expectation of success, because one would have reasonably expected that the replacement of
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with a
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at the R2 position of the modified compound 85 of ‘970 patent in view of Patani et al. would have successfully treat NSD2 mediated disease or condition.
With respect to “wherein R2 is
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” in claim 7, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the compound 85 of ‘970 patent in view of Patani et al. as set forth above by replacing
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with
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at the R2 position of Formula (I) of ‘970 patent. One would have been motivated to do so, because ‘970 patent clearly teaches a list of suitable R2, including –(CRaRb)r-C(=O)-NR12R13 with the structure of:
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and those that R12 and R13 can join together to form a 5-6 membered heterocyclic ring that is unsubstituted or substituted with C1-4 alkyl, that can arrive a compound of Formula (I) useful for inhibiting NSD2; and specifically teaches a compound 86 (“
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”) that is a compound of Formula (I) containing
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at R2; and the fact that Patni et al. teaches the replacement of hydrogen with hydroxyl, which is a bioisosteric replacement technique based on Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres, can results in analogues with retention of biological activity. One would have a reasonable expectation of success, because one would have reasonably expected that the replacement of the R12R13 moiety of
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with a R12R13 that is a morpholinyl substituted with methyl (
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) at the R2 position of the modified compound 85 of ‘970 patent in view of Patani et al. would have successfully treat NSD2 mediated disease or condition.
With respect to “wherein R2 is
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, 1H-tetrazolyl, 2H-tetrazoly, pyridyl, trifluoromethylpyridyl or phenyl” in claim 8, , it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the compound 85 of ‘970 patent in view of Patani et al. as set forth above by replacing
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with a pyridyl at the R2 position of Formula (I) of ‘970 patent. One would have been motivated to do so, because ‘970 patent clearly teaches a list of suitable R2, including –(CRaRb)r-C(=O)-NR12R13 and 5-6 membered heterocyclylC0-6alkyl, that can arrive a compound of Formula (I) useful for treating NSD2 mediated disease or condition; and specifically teaches compound 271 (“
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”) that is a compound of Formula (I) containing a pyridyl ring at R2. One would have a reasonable expectation of success, because one would have reasonably expected that the replacement of
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with a pyridyl at the R2 position of the modified compound 85 of ‘970 patent in view of Patani et al. would have successfully inhibits NSD2.
With respect to “wherein at least two of R7, R8, R9 and R10 are not hydrogen” in claim 10, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the compound 85 of ‘970 patent in view of Patani et al. as set forth above by replacing the hydrogen with a C1-4 alkyl at the R10 position of Formula (I) of ‘970 patent. One would have been motivated to do so, because ‘970 patent clearly teaches a list of suitable alternatives, including hydrogen and C1-4 alkyl, at the R10 position that can arrive a compound of Formula (I) useful for treating NSD2 mediated disease or condition. One would have a reasonable expectation of success, because one would have reasonably expected that the replacement of hydrogen with a methyl at the R10 position of the modified compound 85 of ‘970 patent in view of Patani et al. would have successfully treat NSD2 mediated disease or condition.
With respect to claim 11, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the compound 85 of ‘970 patent in view of Patani et al. as set forth above (see rejection with respect to claim 10) by replacing the
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moiety with a cyclopropyl (
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) as the C3-8cycloalkyl(C0-6 alkyl) at the R8 position of Formula (I) of ‘970 patent. One would have been motivated to do so, because ‘970 patent clearly teaches a list of suitable alternatives, including aryl and C3-8 cycloalkyl(C0-6 alkyl), at the R8 position that can arrive a compound of Formula (I) useful for treating NSD2 mediated disease or condition; and specifically teaches a compound 275 (“
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”) that is a compound of Formula (I) containing a cyclopropyl ring at R8. One would have a reasonable expectation of success, because one would have reasonably expected that the replacement of
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with a cyclopropyl at the R8 position of the further modified compound 85 of ‘970 patent in view of Patani et al. would have successfully treat NSD2 mediated disease or condition.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on August 29, 2025 with respect to the rejection of claims 1-5, 7-8, 10-11 and 13-15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,420,970 B1 (referred to herein as ‘970 patent) in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) have been fully considered but they are not persuasive.
In Summary, applicant argues one would not have expected that the claimed compounds are useful for treating or preventing a disease or condition mediated by MLL1, because the compounds of ‘970 patent are inhibitors of the nuclear SET domain-containing protein 2 (NSD2), and said reference patent only discloses the ability of candidate compounds to reduce cellular H3K36me2 level in multiple myeloma cell lines and in thyroid carcinoma cell lines. Applicant further argues Patani et al. provides no teachings or guidance that would motivate one skilled in the art to modify the teachings of the ‘970 patent.
In response, applicant’s argument is not found persuasive. It may well be true that the compounds taught by ‘970 patent are inhibitors of the nuclear SET domain-containing protein 2; However, the compounds of ‘970 patent are taught to be useful for treating breast cancer as the disease or condition mediated by nuclear SET domain-containing protein 2 (see claim 28 of ‘970 patent); and that is also a disease or condition mediated by MLL1 (see e.g., p. 18, line 15-16 of the instant specification). It is noted that the rejection on the record is based on the claims of ‘970 patent and the teachings of Patani et al. In this case, Patani et al. clearly teaches benzene and pyridine are classical bioisosteres based on the Grimm’s Hydride Displacement Law, and they can be interchanged in medicinal chemistry to arrive at analogues with retention of biological activity (see e.g., p. 3148-3149; and p. 3158, “E. Ring Equivalents” section). In other words, even though Patani et al. does not exemplify the classical bioisosteric replacement using the compound 85 of ‘970 patent, said prior art clearly provides the teachings that would motivate one of ordinary skill in the art to substitute the pyridine ring of the compound 85 of ‘970 patent with a benzene ring in order to arrive at a compound that can inhibit the nuclear SET domain-containing protein 2 for the treatment of cancer, such as breast cancer. Since applicant does not present any evidence or showing that substituting the pyridine ring of the compound 85 of ‘970 patent with a benzene ring would lead to unexpected results (e.g., the modified compound loss the ability to inhibit nuclear SET domain-containing protein 2 for the treatment of cancer), the argument is not found persuasive for the reasons set forth herein.
Therefore, the rejection is maintained but revisited and modified in view of the claim amendments.
Claim 1-2, 10, and 13-15 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,312,353 B2 (referred to herein as ‘353 patent) in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176).
Please note this nonstatutory double patenting rejection is the same as the provisional nonstatutory double patenting rejection over copending Application No. 17/739,855 as set forth in the previous office action. Since the copending application is now an issued U.S. Patent No. 12,357,585 B2 published on July 15, 2025, and do not have the same claim numbers, this nonstatutory double patenting rejection are revisited and modified in light of the issued patent; However, this rejection should be interpretated as being the same as corresponding to the provisional nonstatutory double patenting rejection.
The claims of ‘353 patent are drawn to a method for treating multiple myeloma, comprising administering to a subject in need thereof of such treatment a therapeutically effective amount of a compound of Formula (I):
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, or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof, and said compound includes a compound having the following formula:
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. The claims of ‘353 patent teaches the compound of Formula (I)
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, wherein R2 is, inter alia, 5-9 membered heteroarylC0-6 alkyl, wherein said heteroaryl radical is unsubstituted or substituted by, inter alia, halo; R8 is, inter alia, aryl, wherein said R8 is unsubstituted or substituted by 1-3 R17; R17 is, inter alia, halo; and R10 is hydrogen or -C1-4 alkyl (see reference claims indicated above).
The claims of ‘353 patent does not expressly teach a compound species of Formula (I) instantly claimed.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents (see e.g., “introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar biological activity, and have been classified as either classical or nonclassical, wherein the classical bioisosteres are a series of replacements defined by Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres (see e.g., p. 3148-3149). Patani et al. further teaches the use of the classical bioisosteres benzene and pyridine resulted in analogues with retention of biological activity within different series of pharmacological agents (see e.g., p. 3158, “E. Ring Equivalents” section). Patani et al. further teaches the trivalent substitution of -CH= with -N= is commonly used in modern drug design, for example, said substitution in the (benzothiazolylbenzyl)phosphonate derivatives retained vasodilatory activity as shown below:
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(see e.g., page 3159, right column, under “trivalent ring equivalent” to page 3160, left column, table 30).
In the present case, the difference between the compound of ‘353 patent and the expanded compound species of instant Formula (I) lies on the pyridine ring attached to the piperidine moiety and R8 of the compound of ‘353 patent as shown below (see shaded):
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to select the compound of ‘353 patent, and then modify said compound by replacing the pyridine ring attached to the piperidine moiety with a benzene ring as taught by Patani et al., and removing the -O-methyl substituted on the phenyl ring at the R8 position as taught by ‘353 patent . One would have been motivated to do so, because Patani et al. teaches the replacement of pyridine with benzene, which is a bioisosteric replacement technique based on Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres, can results in analogues with retention of biological activity; and ‘353 patent teaches R8 can be unsubstituted or substituted by 1-3 R17. One would have a reasonable expectation of success, because one would have reasonably expected that modifying the pyridine ring of compound of ‘855 application with a benzene ring, and removing the -O-methyl substituted on the phenyl ring at the R8 position as taught by ‘353 patent would have successfully arrive at a compound useful for treating a disease or condition mediated by nuclear SET domain-containing protein 2, and therefore the modified compound of ‘353 patent in view of Patani et al. can successfully incorporate into a pharmaceutical composition with a pharmaceutically acceptable carrier, and combine with another compound species of Formula (I) of ‘353 patent as the anti-cancer agent as it is well-understood, routine, and conventional in the art.
Please note the modified compound of ‘353 patent in view of Patani et al., in this case, a compound having the structure of:
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, is a compound of Formula (I)
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, wherein A is N; R1 is H; n is 1; R2 is
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, and that meets the limitation of “R2 is … (vi) 6 membered heteroaryl… wherein each said…heteroaryl radical is independently…substituted by… halo”; R3b, R3a, R4a, R4b, R5a, R5b, R6a and R6b are independently hydrogen; R7, R9 and R10 are independently hydrogen; R8 is phenyl, wherein said phenyl is independently substituted with 2 R20, wherein R20 is fluoro and that meets the limitation of “-halo”.
With respect to claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the compound of ‘855 application and Patani et al. as set forth above by replacing
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with
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at the R2 position of Formula (I) ‘353 patent . One would have been motivated to do so, because ‘353 patent clearly teaches a list of suitable R2, including 5-9 membered heteroarylC0-6 alkyl, wherein said heteroaryl radical is unsubstituted or substituted by, inter alia, halo, that can arrive a compound of Formula (I) useful for treating multiple myeloma. One would have a reasonable expectation of success, because one would have reasonably expected that the replacement of the substituted pyridine ring
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with an unsubstituted pyridine
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at the R2 position of the modified compound of ‘353 patent in view of Patani et al. would have successfully treat multiple myeloma.
With respect to “wherein at least two of R7, R8, R9 and R10 are not hydrogen” in claim 10, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the compound of ‘353 patent in view of Patani et al. as set forth above by replacing the hydrogen with a C1-4 alkyl at the R10 position of Formula (I) of ‘855 application. One would have been motivated to do so, because ‘353 patent clearly teaches a list of suitable alternatives, including hydrogen and C1-4 alkyl, at the R10 position that can arrive a compound of Formula (I) useful for treating multiple myeloma. One would have a reasonable expectation of success, because one would have reasonably expected that the replacement of hydrogen with a methyl at the R10 position of the modified compound of ‘353 patent in view of Patani et al. would have successfully treat multiple myeloma.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed on August 29, 2025 with respect to the provisional rejection of claims 1-2, 10, and 13-15 on the ground of nonstatutory double patenting as being unpatentable over claims 27-41 of copending Application No. 17/739,855 (referred to herein as ‘855 application) in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) have been fully considered but they are not persuasive.
In Summary, applicant argues one would not have expected that the claimed compounds are useful for treating or preventing a disease or condition mediated by MLL1, because the compounds of ‘855 application are inhibitors of the nuclear SET domain-containing protein 2 (NSD2), and said reference patent only discloses the ability of candidate compounds to reduce cellular H3K36me2 level in multiple myeloma cell lines and in thyroid carcinoma cell lines. Applicant further argues Patani et al. provides no teachings or guidance that would motivate one skilled in the art to modify the teachings of the ‘855 application.
In response, applicant’s argument is not found persuasive. First of all, the Examiner noted that the ‘855 application is now an issued U.S. Patent No. 12,312,353 B2 published on May 27, 2025, which do not have the same claim numbers. Therefore, the previous rejection has been revisited and modified in view of the issued patent for the reasons set forth herein; However, the rejection should be interpretated as being the same as corresponding to the provisional nonstatutory double patenting rejection sets forth in the Non-Final Office Action mailed on May 29, 2025.
Second, it may well be true that the compounds taught by ‘855 application (‘353 patent) are inhibitors of the nuclear SET domain-containing protein 2 in the disclosure; However, the compounds of ‘855 application (‘353 patent) are taught to be useful for treating multiple myeloma in the claims; and that is also a disease or condition mediated by MLL1 (see e.g., p. 14, line 22 of the instant specification). It is noted that the rejection on the record is based on the claims of ‘855 application (‘353 patent) and the teachings of Patani et al. In this case, Patani et al. clearly teaches benzene and pyridine are classical bioisosteres based on the Grimm’s Hydride Displacement Law, and they can be interchanged in medicinal chemistry to arrive at analogues with retention of biological activity (see e.g., p. 3148-3149; and p. 3158, “E. Ring Equivalents” section). In other words, even though Patani et al. does not exemplify the classical bioisosteric replacement using the compound of ‘855 application (‘353 patent), said prior art clearly provides the teachings that would motivate one of ordinary skill in the art to substitute the pyridine ring of the compound of ‘855 application (‘353 patent) with a benzene ring in order to arrive at a compound that can inhibit the nuclear SET domain-containing protein 2. Since applicant does not present any evidence or showing that substituting the pyridine ring of the compound of ‘855 application (‘353 patent) with a benzene ring would lead to unexpected results (e.g., the compound loss the ability to inhibit nuclear SET domain-containing protein 2), the argument is not found persuasive for the reasons set forth herein.
Therefore, the rejection is maintained but revisited and modified in view of the claim amendments.
Free of the Art
Claims 6, 9, 12, and 21 are free of the art.
Claim 6, 9 and 12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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).
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 Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
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