DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
This application is a divisional application of U.S. Application No. 16/836,832,
filed March 31, 2020, which is a divisional application of U.S. Application No. 16/195,550, filed November 19, 2018, now U.S. Patent No. 10,669,257, which is a divisional application of U.S. Application No. 15/786,334, filed October 17, 2017, now U.S. Patent No. 10,189,814, which is a divisional application of U.S. Application No. 15/040,980, filed February 10, 2016, now U.S. Patent No. 9,822,094, which is a divisional application of U.S. Application No. 13/952,386, filed July 26, 2013, now U.S. Patent No. 9,309,219, which is a divisional application of U.S. Application No. 13/025,105, filed February 10, 2011, now U.S. Patent No. 8,518,972, which
claims priority to U.S. Provisional Application No. 61/303,618, filed February 11, 2010.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 6 November, 2025, in the matter of Application N° 17/867,294. Said documents have been entered on the record.
Claims 26, 29, and 32 are canceled. No new matter was introduced.
Thus, Claims 24-25, 26-28, and 30-31 represent all claims currently under consideration. Response to Arguments
Applicant’s arguments, see Remarks section I, filed 6 November, 2025, with respect to the rejections of Claims 25, 28, and 31 have been fully considered and are persuasive. The rejection of Claims 25, 28, and 31 under 35 U.S.C. 112(d) has been withdrawn.
Applicant's arguments for Claims rejected under 35 U.S.C. § 103 and Double Patenting have also been fully considered but they are not persuasive.
The prior art of record (Ruchelman, sharing the same Assignee and several of the same inventors) constitutes highly relevant evidence of the state of the art at the time of filing. As such, the reference provides a natural starting point for assessing obviousness and nonstatutory double patenting. Applicant’s position that a “lead compound” must be formally identified is not consistent with controlling precedent. Where the reference itself teaches structurally close analogs and provides explicit motivation to vary substituents within a common scaffold, an express lead-compound designation is unnecessary. The proper analysis is whether a person skilled in the art would have been motivated to select or modify the prior art compounds with a reasonable expectation of achieving predictable results.
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Applicant asserts that the prior art “focused” on di-oxo-isoindoline systems and therefore would not have led a person skilled in the art to the mono-oxo-isoindoline core of the instant claims (Remarks, Pg. 7.) This is not persuasive. Although the reference includes numerous exemplary di-oxo species, the reference expressly discloses both di-oxo (e.g., Example 1 species) and mono-oxo variants (e.g., Example 2 species) within its broader genus. The fact that the majority of exemplified species employ the di-oxo core does not negate the clear teaching – within the same reference and by the same inventors – that mono-oxo isoindoline structures were expressly suggested and suitable.
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Furthermore, the prior art exemplifies a species shown top left, differing from an instantly claimed compound shown bottom left, by the inclusion of a methyl off the linking carbon. The presence of this methyl is only exemplified in these two examples demonstrating that non-methylated analogs were well within the expected scope of the genus. Where the genus teaches both options and the claimed invention merely selects one permitted alternative (i.e., hydrogen instead of methyl), the claimed species constitutes an obvious variant of the prior art.
It is also well-established that substitution or removal of small alkyl groups (e.g., methyl/de-methyl variants) constitutes routine optimization in the chemical arts, particularly where the core scaffold remains unchanged. A person skilled in the art would have understood that removing a single methyl and hydrogen as permissible substituents – would represent an expected, routine modification to optimize physicochemical or pharmacokinetic features. Applicant provides no evidence that such modification would yield unpredictable or unexpected results.
Accordingly, the rejections under 35 U.S.C. § 103 and Double Patenting are maintained.
Claim Rejections - 35 USC § 103 (MAINTAINED)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 24-25, 27-28, and 30-31 are rejected under pre-AIA 35 U.S.C. 103(a) as being obvious over Ruchelman, Muller, and Man (WO 2008/115516 A2, published 25 September, 2008, cited in the IDS), hereinafter Ruchelman.
The applied reference has a common Assignee and Inventors with the instant application.
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Regarding Claim 24, Ruchelman teaches Formula I (‘516, Pg. 5, Para 22), shown top right, wherein Y is CH2, and R1 can be an aryl, heteroaryl, or heterocyclyl, which encompasses the instantly claimed Formula II (instant Claim 24), shown bottom right, wherein R4 is benzothiazole, quinoline, isoquinoline, naphthalene, 2,3-dihydro-1H-indene, benzo[d][1,2,3]triazole, imidazo[1,2- a]pyridine, benzofuran, 2,3-dihydrobenzofuran, benzothiophene, benzo[d]oxazole, isoindoline, or chroman.
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Regarding Claim 25, Ruchelman teaches the naphthalene compound (‘516, Pg. 10, Para 38, Row 5) shown top left. This differs from the instantly claimed compound (instant Claim 25, Row 4, Structure 1) shown bottom left, with the inclusion of a methyl off the linking carbon.
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Furthermore, Ruchelman teaches the benzofuran compound (‘516, Pg. 10, Para 38, Row 4, Structure 3) shown top left. This differs from the instantly claimed compound (instant Claim 25, Row 1, Structure 2) shown bottom left, with the inclusion of a methyl off the linking carbon.
Ruchelman discloses a genus encompassing both methylated and non-methylated linkers. Among the 72 exemplified species, only these two examples exhibit a methyl substituent at the linking carbon, all others lack such methylation or any other substitution. This strongly suggests that non-methylated linkers were well within the ordinary and expected scope of the genus. Therefore, a person of ordinary skill in the art would have found it obvious to omit the methyl group, consistent with both routine optimization and what is highly suggested by the exemplified species of Ruchelman.
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Additionally, Ruchelman teaches the following species (‘516, Pg. 10, Para 38, Row 3, Structure 3, and Row 4, Structure 1), shown to the left, wherein the phenyl substituents are all hydrogen or wherein chlorine atoms are positioned at the 3-and 4-positions, respectively. The proviso of the instant claims excludes such arrangements; however, modification of phenyl ring substitution patterns (e.g., exchanging a hydrogen atom for a halogen, altering halogen position, or introducing a different substituent) is a common and routine optimization in the chemical arts. A person of ordinary skill would have found it obvious to adjust the substituents on the phenyl ring of the reference species to produce a non-proviso embodiment falling within the scope of the claims, motivated by well-known structure activity relationship studies aimed at tuning electronic and steric properties.
Regarding Claims 27-28, Ruchelman teaches pharmaceutical compositions and dosage forms can further comprise one or more excipients (‘516, Pg. 39, Para 124.)
Regarding Claims 30-31, Ruchelman teaches a method of treating, managing or preventing a disease or disorder comprising administering to a patient a compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the disease or disorder is cancer, a disorder associated with angiogenesis, pain, macular degeneration or a related syndrome, a skin disease, a pulmonary disorder, an asbestos-related disorder, a parasitic disease, an immunodeficiency disorder, a CNS disorder, CNS injury, atherosclerosis or a related disorder, dysfunctional sleep or a related disorder, an infectious disease, hemoglobinopathy or a related disorder, or a TNFα. related disorder. (‘516, Pg. 87, Claim 19.)
Accordingly, the modification necessary to arrive at the presently claimed compounds – whether through omission of a small alkyl substituent or minor adjustment of aromatic substituents – represent routine optimization strategies well within the skill of the ordinary artisan. These variations are expressly permitted or suggested within the disclosed genus of Ruchelman, which encompasses both the methylated and non-methylated linkers, as well as a range of aromatic substitution patterns. Given the close structural similarity between the exemplified species of Ruchelman and the claimed compounds, and the well-established motivation to explore minor structural variants to fine-tune chemical properties, there would have been a reasonable expectation of success. Thus, the claimed subject matter is rendered prima facie obvious.
Double Patenting (MAINTAINED)
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 24-25, 27-28, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-3, 5-6, 12, 14, and 16-17 of U.S. Patent No. 8,153,659 (linked to the above referenced WO 2008/115516 A2, both cited in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed compounds and methods of use are suggested and/or exemplified within the patent and are therefore anticipated or an obvious variation of the reference claims.
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Patent ‘659 teaches the formula shown top right (‘659, Claim 1) , wherein Y is CH2 (‘659, Claims 1 and 3), and R1 is a heteroaryl (‘659, Claims 1 and 5-6), and the formula shown middle right, (‘659, Claim 12) wherein, n1 is 1 (‘659, Claims 12 and 14), Y is CH2 (‘659, Claims 12 and 14), and R5 is a heteroaryl. Both patented formulas encompasses the instantly claimed Formula II (instant Claim 24), shown on the previous page, bottom right.
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Patent ‘659 teaches the benzofuran compound (‘659, Claims 1 and 16) shown top left, which is identical to the instantly claimed compound (instant Claim 25, Row 1, Structure 2.)
Patent ‘659 teaches pharmaceutical compositions and dosage forms can further comprise one or more excipients (‘659, Claim 17, and Col 37, final paragraph.)
Patent ‘659 teaches a method of treating, managing or preventing a disease or disorder comprising administering to a patient a compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the disease or disorder is cancer, a disorder associated with angiogenesis, pain, macular degeneration or a related syndrome, a skin disease, a pulmonary disorder, an asbestos-related disorder, a parasitic disease, an immunodeficiency disorder, a CNS disorder, CNS injury, atherosclerosis or a related disorder, dysfunctional sleep or a related disorder, an infectious disease, hemoglobinopathy or a related disorder, or a TNFα. related disorder. (‘659, §4.2 Methods of Treatment, Prevention, and Management, Col 20-28.)
Conclusion
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 Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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/D.M.N./Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627