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 .
Status of Claims
Pursuant to the amendment, filed on June 2, 2025, claims 2, 3, 5-9, 12, 14-16, 19-22, 24-27, 29-48, 50-57, 60-79, 81-86, 90-92, and 94-96 are cancelled and claims 97-99 have been added. Claims 1, 4, 10-11, 13, 17-18, 23, 28, 49, 58-59, 80, 87-89, 93, and 97-99 are pending.
Priority
This application, filed on September 12, 2024, is a National Stage entry from International Application No. PCT/US2023/064231, filed on March 3, 2023, which claims benefit to Provisional Application Nos. 63/363,144, filed on April 18, 2022, and 63/269,329, filed on Mar. 14, 2022.
Claim Interpretation
Claim 1 recites, R1a is selected from hydrogen, unsubstituted C2-4 alkyl, etc. and R1b is hydrogen, unsubstituted C1-4 alkyl, etc. The claim also recites that when R1b is hydrogen, then R1a is selected from deuterium, unsubstituted C2-4 alkyl, etc. The claim does not recite what R1b is when R1a is hydrogen, therefore the claim is construed as R1a encompassing the entire scope of its grouping when R1b is an unsubstituted C1-4 alkyl, i.e., if R1b is an unsubstituted C1-4 alkyl, R1a is hydrogen, deuterium, etc.
Claim Rejections - 35 USC § 112(b)
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 99 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 99 is directed to a method for preparing the compound of claim 1 and the steps are referenced in “Scheme 1,” which is in the instant specification (p. 48). The written description and the claims are separate statutory requirements. Under modern claim practice, claims must stand alone to define an invention. Ex parte Fressola, 27 USPQ2d 1608 (BPAI 1993). As a result, one of ordinary skill in the art must refer back to the specification to understand what the claimed invention is.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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, 10-11, 17-18, 28, 49, 58-59, 80 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO2010111626 (“Brown”).
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Claim 1 recites a compound of Formula (I) having the structure:
wherein;
Ring A is selected from phenyl, pyridine, etc., and is optionally substituted with one or more substituent independently selected from halogen, unsubstituted C1-4 alkyl, unsubstituted C1-4 alkoxy, etc.;
Ring B is selected from 6-membered monocyclic, 7-membered bicyclic, etc., nitrogen containing heterocycle which is optionally substituted with m amount of R3a wherein m is 0-2;
Ring C is selected from pyridine, phenyl, etc., which is optionally substituted with n amount of R3b wherein n is 0-2;
R1a is selected from hydrogen, unsubstituted C2-4 alkyl, etc.,
R1b is hydrogen, unsubstituted C1-4 alkyl, etc.;
Y1 is O, CH2, etc.;
R2 and R3 are each independently hydrogen, deuterium, etc.; and
R4 is -C(=O)NR5R6 (“amide”) wherein R5 is hydrogen or unsubstituted C1-4 alkyl and R6 is hydrogen, unsubstituted C1-4 alkyl, substituted C1-4 alkyl, unsubstituted monocyclic C3-6 cycloalkyl etc.
Claims 4 and 10 specify Ring A is an optionally substituted phenyl. Claim 11 specifies Ring B is a 6-membered monocyclic nitrogen-containing heterocycle. Claim 17 specifies Ring B is piperazine. Claim 18 specifies the amount of substituents on Ring B and Ring C are in the range of 0-1. Claim 28 specifies Ring C is pyridine. Claim 49 specifies the amide is substituted with R5 as hydrogen and R6 is hydrogen, unsubstituted C1-4 alkyl, unsubstituted monocyclic C3-6 cycloalkyl, etc. Claim 58 specifies Ring C is selected from pyridine wherein the N atom is positioned ortho to the bond between Ring C and Ring B, i.e,
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. Claim 59 specifies R1a is hydrogen and R1b is unsubstituted C1-4 alkyl. Claim 80 specifies R2 and R3 are each hydrogen.
Brown teaches compounds 23-406 (pp. 83-234) were tested against PARP for inhibition (pp. 237-247). The compounds taught by Brown overlap wherein R2 and R3 are independently hydrogen, Y1 is O, and R1a and R1b are hydrogen and C1-4 alkyl, respectively. All the compounds discussed herein, except for 390-393, 395-397, have Ring B as piperazine, whereas compounds 390-393, 395-397 have Ring B as piperidine. Below are the species taught by Brown that read on the genus of the instant claims. The compounds are grouped together based on their rings and substitution patterns, relative to the instant claims, and are described in the parenthetical:
161-164, 398 (Ring A is phenyl substituted with C1-4 alkoxy, Ring C is phenyl, and the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
223-225 and 249-250 (Ring A and C are phenyl and the amide is monosubstituted with C1-4 alkyl);
235-236, 238 (Ring A is phenyl, Ring C is pyridine wherein the N atom is ortho to the bond between Ring B and Ring C, and the amide is monosubstituted with C1-4 alkyl);
378-379 (Ring A and C are phenyl and the amide is disubstituted with C1-4 alkyl);
257-262, 305, 356, 358 (Ring A is phenyl substituted with C1-4 alkyl, Ring C is phenyl, and the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
271-273, 308-311, 335-338 (Ring A is phenyl substituted with halogen, Ring C is phenyl, and amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
314-317 (Ring A is phenyl substituted with halogen, Ring C is pyridine wherein the N atom is positioned ortho to the bond between Ring B and Ring C, and the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
360-361, 365-366, 372-373, 399 (Ring A is phenyl substituted with C1-4 alkoxy, Ring C is phenyl substituted with halogen, the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
362-364 (Ring A is phenyl substituted with C1-4 alkoxy, Ring C is phenyl substituted with C1-4 alkyl, the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
371 (Ring A is phenyl, Ring C is phenyl substituted with halogen, and amide is monosubstituted with C1-4 alkyl);
380-383, 387-388 (Ring A is phenyl substituted with C1-4 alkyl, Ring C is phenyl substituted with halogen, the amide substituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
384-386 (Ring A is phenyl substituted with C1-4 alkyl, Ring C is phenyl substituted with C1-4 alkyl, the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
390-393, 395-397 (Ring A is phenyl, Ring B is piperidine, Ring C is phenyl, and the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
400-402 (Ring A is phenyl substituted with C1-4 alkoxy, Ring C is phenyl substituted with C1-4 alkyl, and the amide is monosubstituted with C1-4 alkyl or monocyclic C3-6 cycloalkyl);
403-404 (Ring A is phenyl substituted with C1-4 haloalkoxy, Ring C is phenyl, and the amide is monosubstituted with C1-4 alkyl);
405 (Ring A is phenyl substituted with C1-4 haloalkoxy, Ring C is phenyl substituted with halogen, and the amide is monosubstituted with C1-4 alkyl); and
406 (Ring A is phenyl substituted with C1-4 haloalkoxy, Ring C is phenyl substituted with C1-4 alkyl, and the amide is monosubstituted with C1-4 alkyl).
For example, compound 235 (
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) is a species of the instant claims, because:
Ring A is phenyl (claims 1, 4, and 10);
Ring B is the 6-membered monocyclic piperazine (claims 1, 11, 17-18);
Ring C is pyridine (claims 1, 28, 58);
R1a is hydrogen and R1b is unsubstituted C1-4 alkyl (claims 1, 59);
Y1 is O (claim 1);
R2 and R3 are each independently hydrogen (claim 1 and 80); and
R4 is the amide wherein R5 is hydrogen and R6 is unsubstituted C1-4 alkyl (claims 1 and 49).
Accordingly, claims 1, 4, 10-11, 17-18, 28, 49, 58-59, 80 are anticipated by Brown.
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 87-89 and 93 are rejected under 35 U.S.C. 103 as being unpatentable over Brown.
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Brown teaches compounds 223 and 235 as PARP inhibitors (Abstract, ¶[0008], pp. 83-234) and are shown below.
[AltContent: textbox (235)][AltContent: textbox (223)]
Brown also teaches pharmaceutical compositions of the compounds and a method of treating diseases associated with reduced PARP activity (¶¶ [0017], [0025], [0167], and [0195]; claim 81). The disease state is selected from a group consisting of cancers wherein the cancer is pancreatic, prostate, colon, colorectal, etc. (¶[0178]; claims 84 and 95). The compounds are also tested against a Jurkat cell line, an acute T-cell Leukemia cell line (¶[0727]).
Brown is analogous art to the claimed invention because it is in the same field of preparing compounds that are PARP inhibitors and are useful for treating cancer. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) to modify compounds 223 and 225 and arrive at the compounds instantly claimed. Compounds 223 and 235 are homologs of the species in instant claims 87 (Claims, p. 12, 1st column, 1st and 3rd compounds) and 88 (Claims, p. 21, 1st and 2nd columns, 3rd and 7th compounds), and are therefore of sufficiently close structural similarity that there is a presumed expectation that the compounds possess similar properties (MPEP §2144.09(II)). Accordingly, claims 87-88 are prima facie obvious.
Regarding claim 89, Brown teaches compositions that include a predetermined quantity of the therapeutically active compound in association with the required pharmaceutical carrier, vehicle, diluent, or excipient (vide supra).
Regarding claim 93, Brown teaches a method for treating a cancer by administering a composition including a compound to a subject (vide supra).
Allowable Subject Matter
Claims 13 and 97-98 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.
Claim 13 specifies that Ring B is a bicyclic 7-membered or 8-membered nitrogen-containing heterocycle. Claim 97 recites compound
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, and claim 98 recites the stereoisomers of the same compound. Brown is close prior art which teaches compound 314
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, which is substituted with a fluorine substituent on Ring A, but the fluorine substituent is not in the same position as the compound recited in instant claim 97. Additionally, Ring C of 314 is an unsubstituted pyridine, and the N atom is positioned ortho to the bond between Ring B and Ring C. There is no teaching, suggestion, or motivation to reposition the fluorine substituent of Ring A, or the pyridine of Ring C, wherein the N atom is positioned meta to the bond between Ring B and Ring C, similar to the compound recited in instant claims 97-98. Additionally, there is no teaching, suggestion, or motivation to further substitute the pyridine of Ring C with a fluorine positioned meta to the amide.
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, 4, 10-11, 17-18, 23, 28, 49, 58-59, 80, 87-89, 93, and 99 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,054,479 (“ ‘479 “) in view of Brown. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over ‘479 in view of Brown.
Claims 1-4 of ‘479 recite compound
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and a composition comprising the same compound and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.
‘479 does not teach a method of administering the compound to treat cancer in a subject.
Brown teaches pharmaceutical compositions of the compounds and a method of treating diseases associated with reduced PARP activity (¶¶ [0017], [0025], [0167], and [0195]; claim 81). The disease state is selected from a group consisting of cancers wherein the cancer is pancreatic, prostate, colon, colorectal, etc. (¶[0178]; claims 84 and 95). The compounds are also tested against a Jurkat cell line, an acute T-cell Leukemia cell line (¶[0727]).
It would have been prima facie obvious to a PHOSITA to obtain the compound recited in ‘479 and include it in a composition to include with a pharmaceutically acceptable carrier and administer the composition to treat a subject having cancer, based on the teachings of Brown.
Conclusion
Claims 1, 4, 10, 11, 17, 18, 23, 28, 49, 58, 59, 80, 87-89, 93, and 99 are rejected.
Claims 13 and 97-98 contain allowable subject matter over the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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