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 present Application, filed October 1, 2024, claims the benefit of U.S. Provisional Patent Application Nos. 63/697,154, 63/566,213, 63/633,660, 63/665,990, 63/546,442, 63/542,051, filed September 20, 2024, March 15, 2024, April 12, 2024, June 28, 2024, October 30, 2023, and October 2, 2023, respectively.
Status of the Claims
Originally filed claims 1-36 are currently pending.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 22 is indefinite:
Claim 22 is 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.
Claim 22 is indefinite for labeling multiple stereocenters on recited compounds with the labels, “abs” or “or1.” Claim 22 recites twenty-three individual compounds, many of which have a stereocenter that is indicated according to standard chemical line drawing convention with one bond having a solid-wedged or dashed-wedged line. Some of the stereocenters are labeled with IUPAC (Cahn-Ingold-Prelog (CIP)) absolute stereochemistry (S) or (R) designations. These designations are understood as labeling the stereocenter according to CIP rules, and also as confirming that the stereochemistry indicated by the drawing is required.
Some stereocenters are instead labeled “abs” or “or1.” These are tentatively understood as being V3000 molfile enhanced stereochemistry designations, where “abs” is an abbreviation for absolute and indicates that the stereocenter must be that which is depicted by the line drawing. That being the case, it would be unclear what difference in meaning, if any is associated with an “abs” label and an appropriate (S) or (R) label. If there is no difference, other than that “abs” doesn’t indicate whether the stereocenter is (S) or (R), but all require the defined stereochemistry, it is unclear why different labeling systems are used. Furthermore, some stereocenters are indicated by line drawing as having a specific stereochemistry, but carry no designation label. As such, at first glance the following labeling schemes appear to carry the same meaning: (i) a CIP label ((S) or (R)), (ii) an “abs” label, and (iii) no label but stereochemistry indicated by drawing. This creates confusion as to whether these three different designations actually do carry the same meaning, or convey some difference in meaning
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Similarly, “or1” is tentatively understood to mean, in V3000 molfile designation, that the
indicated stereochemistry can optionally be inverted. However, unless the claim requires some degree of stereochemical purity that is not indicated, it would be unclear how a stereocenter with drawn stereochemistry but labeled “or1” differs from a stereocenter of unspecified stereochemistry. Further to that point, claim 22 does recite a number of stereocenters of unspecified stereochemistry.
In short, claim 22 is indefinite due to the mixing of conventional CIP stereocenter labeling with what is apparently V3000 molfile enhanced stereochemistry labeling, particularly since it is unclear what differences, if any, the different usages are meant to convey.
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.
Claims 1, 3-5, and 7-17 are obvious over Cheng and Brown:
Claims 1, 3-5, and 7-17 are rejected under 35 U.S.C. § 103 as being unpatentable over International Patent Application Publication No. WO2023/088233 to Cheng et al. (hereinafter, “Cheng”), in view of the non-patent publication, Bioisosteres in Medicinal Chemistry, Wiley-VCH Verlag GmbH & Co., pgs. 7, 9, 17-19, and 131 (2012), edited by Brown (hereinafter, “Brown”).
Claim 1 recites a compound of Formula (I) where Rings A and B and the other variable moieties are as defined.
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Cheng teaches, inter alia, benzisoxazole sulfonamide compounds of formula (III)
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where the variable moieties are as defined (paragraph [00238]). Of note, X is selected from -O- and -N(R7)-. .In a specific example, Cheng teaches 2-methoxy-N-(4-methoxy-6-(thiazol-2-yloxy)benzo[d]isoxazol-3-yl)benzenesulfonamide (Compound 60 – paragraph [00597]), and which is nearly a compound of instant Formula (I) except that the moiety linking the central benzoxazole ring and instant Ring A is oxygen rather than nitrogen.
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Cheng further teaches that Compound 60 is in the category of highest activity (<10 nM IC50 toward KAT6A, Table 2) and has among the highest cellular permeability of the compounds tested (Table 4, pg. 228). As such, compound 60 would have been reasonably selected as a compound for further development. Furthermore, it would have been obvious to modify compound 60 by replacing the linking ether oxygen with a secondary amine, because a secondary amine is known as a classical bioisosteric replacement for an ethereal oxygen group. See, for example, Brown.
Brown teaches that an ethereal oxygen and a secondary amine are classical bivalent bioisosteres (pg. 17, Section 2.3 .2, first several lines).
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Brown further teaches that bioisosteres are structural moieties which fit the broadest definition of isosteres (e.g. groups having the same number and arrangement of electrons) and have the same type of biological properties (pg. 7, final paragraph). Brown further teaches that bioisosteric replacement (e.g. ethereal oxygen with secondary amine) is common in medicinal chemistry, such as for lead optimization (pg. 9, section 1.4) or to avoid patented structural features (pg. 131, first paragraph). Thus, a person of ordinary skill in the art would have had a reasonable expectation of success in maintaining biological activity of the compound while replacing the ether oxygen linker of a highly active Cheng compound (e.g. Cheng Compound 60) with a secondary amine, in order to further develop the molecule as a lead compound and/or to avoid patented structural features.
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Modified Cheng Compound 60 is a compound of instant claim 1, Formula (I), where Ring B is phenyl and any of R6-R9 is 2-methoxy; R1 is hydrogen and R2 is methoxy; R10 is hydrogen; Ring A is C-linked 1,3-thiazole; and R3-R5 is each hydrogen.
With respect to claims 3-4, instant Ring B of modified Cheng compound 60 is phenyl. With respect to claim 5, instant R3 of modified Cheng compound 60 is hydrogen. With respect to claims 7-11, instant R4 and R5 of modified Cheng compound 60 is each hydrogen. With respect to claims 12-16, R6 and R7 of modified Cheng compound 60 can be characterized as hydrogen and methoxy, or vice versa. With respect to claim 17, instant R8 of modified Cheng compound 60 is hydrogen, and all other elements are optional.
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 1-36 are provisionally rejected for nonstatutory double patenting over the ’024 application and Rai:
Claims 1-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/210024 (hereinafter, “the ’024 application”), in view of U.S. Patent Application Publication No. 2023/0303580 to Rai et al. (hereinafter, “Rai”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ’024 application recite compounds that are species of instant Formula (I). Claim 1 of the ’024 application is substantially equivalent to instant claim 21, with the exception that the alternatives for R8 are narrowed and deuterium substitution is expressly permitted. As such, instant claims 1-21 plainly have extensive overlap with claim 1 of the ’024 application. Moreover, many of the individual species recited in claim 11 of the ’024 application are identical to species recited in instant claims 22-31. With respect to instant claim 32, claims 16-18 of the ’024 application recite pharmaceutical compositions comprising the recited compounds. With respect to instant claims 33-36, the claims of the ’024 application do not recite methods for treating cancer, but such methods using the compounds of the ’024 application would have been obvious because it was well-known in the art that administration of KAT inhibitors is potentially useful in the treatment of cancer. See, for example, Rai.
Rai teaches various benzoisoxazole inhibitors of KAT6A, similar in structure to the compounds of the ’024 application (Abstract, paragraph [0573]). Rai further teaches methods for treating cancer, including breast cancer, involving administration of such compounds to a subject afflicted with cancer (paragraphs [0382]-[0383]). It thus would have been obvious to apply such a method to the functionally and structurally similar compounds of the ’024 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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