DETAILED ACTION
Notice of 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 in the reply filed on 7/29/2026 is acknowledged. The requirement is still deemed proper and is therefore made FINAL.
Claims 20-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election without traverse of a single species in the reply filed on 7/29/2026 is also acknowledged.
As indicated by Applicant, the elected species reads upon claims 1-10, 13-14 and 16-19. However, Applicant’s elected species, a compound of Example 6 having the following structure:
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entails a compound of formula (I) wherein o is 0 and, as such, R1 is absent. Although each of claims 2 and 11-12 further limit R1, the claims do not further limit o, which can still be 0 and, as such, R1 can still be absent in each of claims 2 and 11-12. Similarly, while claim 18 further limits R3 as recited by claim 7, claim 18 does not further limit p, which can still be 0 and, as such, R3 can still be absent in claim 18.
Accordingly, the elected species is determined to read on claims 1-14 and 16-19.
Expansion of Election of Species Requirement
As indicated above, the elected species reads upon claims 1-14 and 16-19.
The elected species has been searched and is deemed to be free of the prior art and non-obvious.
Accordingly, the search has been expanded as called for under current Office Markush practice – a compound-by-compound search – to include at least a single additional species (M.P.E.P. § 803.02), which identified several prior art compounds differing from the instantly claimed compounds in comprising a thienopyridine core as opposed to a thienopyrimidine core, namely:
(a) Dai et al (US 2013/0129677) compounds 84, 145, 189 and 484;
(b) Attaby et al (Curr Bioactive Compounds 9:167-181, 2013) compounds 30a-c and 32a-c;
(c) Wang et al (Bioorg Med Chem Lett 24:1581-1588, 2014; of record) compound 12q;
(d) Ichijo et al (US 2019/0177336) compounds 4, 14 and 41; and
(e) Ahmed et al (Frontiers in Pharmacology 12:790583, 2021) compound TPN-0073027/compound 36.
While the replacement of a thienopyridine core with a thienopyrimidine core is considered a prima facie obvious modification, the Federal Circuit has established a two-prong analysis in determining whether a new chemical compound is prima facie obvious over particular prior art wherein one must first determine whether a chemist of ordinary skill in the art would have selected the asserted prior art compound or compounds as lead compounds, or starting points, for further development efforts (Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280 (Fed. Cir. 2012)). That is, “a prima facie case of obviousness for a chemical compound still, in general, begins with a reasoned identification of a lead compound” (Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353 (Fed. Cir. 2008)). In particular, the Federal Circuit has defined the lead compound as the “compound in the prior art that would be most promising to modify in order to improve upon its… activity and obtain a compound with better activity” (Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350 (Fed. Cir. 2007)) or which would be “a natural choice for further development efforts” (Altana Pharma AG v. Teva Pharms. USA, Inc., 566 F.3d 999 (Fed. Cir. 2009)).
In the instant case, the majority of the prior art compounds comprising a thienopyridine core as opposed to a thienopyrimidine core would not reasonably be considered as lead compounds, or starting points, for further development efforts. Only the following prior art compounds meet this threshold:
Ichijo et al (US 2019/0177336) compound 41 having the following structure:
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; and
Ahmed et al (Frontiers in Pharmacology 12:790583, 2021) compound TPN-0073027/compound 36 having the following structure:
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.
Rejections based on the above compounds follow.
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.
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 1-2, 5-6, 11-12, 14, 17 and 19 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ichijo et al (US 2019/0177336) in view of Williams et al (Foye’s Principles of Medicinal Chemistry, 5th Edition, Pages 59-63, 2002) and Sasaki et al (J Med Chem 46:113-124, 2003).
Claim 1 is drawn to a compound of formula (I), which embraces the following compound species:
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wherein ring A is an aromatic heterocycle; ring B is a ring formed by a 5-12 membered saturated aliphatic heterocycle fused with a benzene ring, wherein ring B is substituted with two C1 alkyl groups; and R1 is absent (i.e., o is 0) – which reads on claims 1-2, 5-6, 11-12, 17 and 19.
Ichijo et al teach “a compound that inhibits the binding between ALS-related mutant SOD1 and Derlin-1” (Paragraph 0001), specifically disclosing 47 inhibitory compounds of which Example 41 is identified as the most potent (i.e., the only compound exhibiting an “activity value (score)” of 3 representing “a compound having higher inhibitory activity than the compound of Example 1” (Paragraph 0192)), having the following structure:
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(Page 34, Example 41),
which differs from the instantly claimed compound in comprising a thienopyridine core as opposed to the instantly claimed thienopyrimidine core, as indicated by arrow.
Yet, as taught by Williams et al “[w]hen a lead compound is first discovered for a particular disease state, it often lacks the required potency and pharmacokinetic properties suitable for making it a viable clinical candidate… The medicinal chemist therefore must modify the compound to reduce or eliminate these undesirable features without losing the desired biological activity. Replacement or modification of functional groups with other groups having similar properties is known as isosteric or bioisosteric replacement” (Page 59). Although it is clear that "the use of bioisosteric replacement (classical or nonclassical) in drug development is highly dependent upon the biological system being investigated” and that “[n]o hard and fast rules exist to determine what bioisosteric replacement is going to work with a given molecule” it is also clear that “some generalizations have been possible” (Page 60). Notably, one such generalization is that –CH= and –N= (which are classic trivalent biosteric groups) can replace each other (Page 61, Table 2.9).
Indeed, Sasaki et al specifically teach the modification of T-98475, a “non-peptide antagonist for the human luteinizing hormone-releasing hormone (LHRH) receptor” (Abstract), in an effort “to identify small-molecule LHRH antagonists with improved efficacy” (Page 114, Column 1) comprising “[s]tarting from T-98475, we... replaced the thieno[2,3-b]pyridine-4-one core with a thieno[2,3-d]pyrimidine-2,4-dione scaffold” (Page 118, Column 2).
Accordingly, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to replace the –CH= group of Example 41 taught by Ichijo et al with an -N= group (i.e., to replace the thienopyridine core taught by Ichijo et al with a thienopyrimidine core) to arrive at the instantly claimed compound. The person of ordinary skill in the art at the time the invention was made would have been motivated to make the bioisosteric modifications to synthesize similar compounds that retain biological activity, but have improved physiochemical properties and better pharmacokinetic behavior, with a reasonable expectation of success.
As such, claims 1-2, 5-6, 11-12, 17 and 19are rejected as prima facie obvious.
Claim 14 is drawn to a pharmaceutical composition, comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.
Ichijo et al further teach that “[t]he present invention still further relates to a... pharmaceutical composition, which comprises the above-described ALS-related mutant SOD1-Derlin-1 binding inhibitor” (Paragraph 0035) further comprising “one or two more pharmaceutical additives” (Paragraph 0114) such as “an excipient component” (Paragraph 0119).
As such, claim 14 is also rejected as prima facie obvious.
Claims 1-2, 5-6, 11-12, 14, 16-17 and 19 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ahmed et al (Frontiers in Pharmacology 12:790583, 2021) in view of Williams et al (Foye’s Principles of Medicinal Chemistry, 5th Edition, Pages 59-63, 2002) and Sasaki et al (J Med Chem 46:113-124, 2003).
Claim 1 is drawn to a compound of formula (I), which embraces the following compound species:
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wherein ring A is an aromatic ring; ring B is a 5 membered saturated aliphatic heterocycle; and R1 is absent (i.e., o is 0) – which reads on claims 1-2, 5-6, 11-12, 16-17 and 19.
Ahmed et al teach “novel inhibitors of M. tuberculosis” (Abstract) specifically identifying TPN-0073027 (aka compound 36) as being “of interest for further development” (Page 7, Column 2), having the following structure:
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(Page 4, Figure 3; see also Page 11, Figure 8),
which differs from the instantly claimed compound in comprising a thienopyridine core as opposed to the instantly claimed thienopyrimidine core, as indicated by arrow.
Yet, as taught by Williams et al “[w]hen a lead compound is first discovered for a particular disease state, it often lacks the required potency and pharmacokinetic properties suitable for making it a viable clinical candidate… The medicinal chemist therefore must modify the compound to reduce or eliminate these undesirable features without losing the desired biological activity. Replacement or modification of functional groups with other groups having similar properties is known as isosteric or bioisosteric replacement” (Page 59). Although it is clear that "the use of bioisosteric replacement (classical or nonclassical) in drug development is highly dependent upon the biological system being investigated” and that “[n]o hard and fast rules exist to determine what bioisosteric replacement is going to work with a given molecule” it is also clear that “some generalizations have been possible” (Page 60). Notably, one such generalization is that –CH= and –N= (which are classic trivalent biosteric groups) can replace each other (Page 61, Table 2.9).
Indeed, Sasaki et al specifically teach the modification of T-98475, a “non-peptide antagonist for the human luteinizing hormone-releasing hormone (LHRH) receptor” (Abstract), in an effort “to identify small-molecule LHRH antagonists with improved efficacy” (Page 114, Column 1) comprising “[s]tarting from T-98475, we... replaced the thieno[2,3-b]pyridine-4-one core with a thieno[2,3-d]pyrimidine-2,4-dione scaffold” (Page 118, Column 2).
Accordingly, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to replace the –CH= group of Example 41 taught by Ichijo et al with an -N= group (i.e., to replace the thienopyridine core taught by Ahmed et al with a thienopyrimidine core) to arrive at the instantly claimed compound. The person of ordinary skill in the art at the time the invention was made would have been motivated to make the bioisosteric modifications to synthesize similar compounds that retain biological activity, but have improved physiochemical properties and better pharmacokinetic behavior, with a reasonable expectation of success.
As such, claims 1-2, 5-6, 11-12, 17 and 19 are rejected as prima facie obvious.
Claim 14 is drawn to a pharmaceutical composition, comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.
Ahmed et al further teach high content screening of compounds in plates having a “final concentration of 10 uM compound, 1% DMSO)” (Page 2, Column 2; see also Cytotoxicity, Page 3, Column 1) – which entails a pharmaceutical composition, comprising the compound and at least one pharmaceutically acceptable excipient (i.e., DMSO).
As such, claim 14 is also rejected as prima facie obvious.
Claim Objections
Since the search has not been expanded beyond the additional species identified above, claims 3-4, 7-10, 13 and 18, which are directed to the elected species but which do not include the single additional species, are objected to, and have not been further examined.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-14 and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16-34 of copending Application No. 18/992,307 in view of Williams et al (Foye’s Principles of Medicinal Chemistry, 5th Edition, Pages 59-63, 2002).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘307 claims are drawn to structurally related compounds of formula (I) (claim 1) and compositions thereof (claim 32), including the following compound species:
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(claim 31), which differs from the instantly claimed compounds in comprising a hydroxy substituent as opposed to the instantly claimed amino substituent, as indicated by arrow.
Yet, as taught by Williams et al “[w]hen a lead compound is first discovered for a particular disease state, it often lacks the required potency and pharmacokinetic properties suitable for making it a viable clinical candidate… The medicinal chemist therefore must modify the compound to reduce or eliminate these undesirable features without losing the desired biological activity. Replacement or modification of functional groups with other groups having similar properties is known as isosteric or bioisosteric replacement” (Page 59). Although it is clear that "the use of bioisosteric replacement (classical or nonclassical) in drug development is highly dependent upon the biological system being investigated” and that “[n]o hard and fast rules exist to determine what bioisosteric replacement is going to work with a given molecule” it is also clear that “some generalizations have been possible” (Page 60). Notably, one such generalization is that -OH and –NH can replace each other (Page 61, Table 2.9).
Accordingly, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to replace the -OH substituent the ‘307 compound with an -NH substituent to arrive at the instantly claimed compound. The person of ordinary skill in the art at the time the invention was made would have been motivated to make the bioisosteric modifications to synthesize similar compounds that retain biological activity, but have improved physiochemical properties and better pharmacokinetic behavior, with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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