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 .
Claims Status
Claims 28-32 and 35-41 are pending in the application.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Terminal Disclaimer
The terminal disclaimers were approved on 9/15/25.
Declaration/Affidavit
The declaration under 37 CFR 1.132 filed 9/5/25 is insufficient to overcome the rejection of claims 28-32 and 35-41 based upon 35 U.S.C. 103 as set forth in the last Office action because: the declaration is not directed to the instant application but is labeled for Application No. 18/354,282.
The declaration addresses the 35 U.S.C. 102 rejection of claim 29 over Dvořáková et al. and the 35 U.S.C. 103 rejection of claim 29 over Jansen et al. (US2014/0357650A1) in view of Zimmerman et al. (US2010/0098633A1) and Jensen et al. (ACS Med. Chem. Lett. 2013, 14, 491-496) that was used in the office action of Application No. 18/354,282.
Therefore, the assertions are not used to address the rejection of the office action of the instant application mailed 6/5/25.
Response to Arguments
Applicant's arguments filed 9/5/25 have been fully considered but they are not persuasive.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 28-32 and 35-41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jansen
et al. (US2014/0357650A1) in view of Zimmerman et al. (US2010/0098633A1) and Jensen et al. (ACS Med. Chem. Lett. 2013, 14, 491-496) and in further view of Dennis Wertz Chemistry - A Molecular Science (eBook) 3rd edition: Custom Labs (2014) https://www.webassign.net/question_assets/wertzcams3/bond_lengths/manual.html and Dvořáková et al. (J. Med. Chem. 2017, 60, 8385-8393) as stated in the office action mailed 6/5/25.
Applicant asserts that the Office Action allegedly discloses the linker
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encompasses the linker
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v = 0 of the instant claims when n is 0 which appears to take the position that this portion of the molecule makes up both a portion of “A” and a portion of the linker “L” as presently claimed.
The Examiner did not assert that the linker
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encompasses the linker “L” of the instant claims but merely stated that the linker
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encompasses the linker portion of “A” which has the structure
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v = 0.
Applicant asserts that the portion of Jansen relied on by the Office action cannot encompass the linker as it does not have “bifunctionalization adapted to form a chemical bond with B and A.”
The Examiner asserts that the quinoline moiety of the compound
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of Jansen I may be substituted with halogenated -C1-6alkyl, -O-C1-6alkyl substituents wherein the -C1-6alkyl, -O-C1-6alkyl groups encompass the linkers of the instant claims that bind a halogen to the
quinoline moiety of
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. Each embodiment does not need to be exemplified.
Further, the instant claims have been amended to cancel the radiohalogens.
With regards to the chelating group the reference Dvořáková et al. was used to teach of the anti-FAP iBody FAP inhibitor comprising
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wherein a linker moiety is attached to the quinoline moiety.
The reference of Zimmerman et al. was used to teach of the FAP- α radiopharmaceuticals
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wherein U is -CN, etc.; G is H, alkyl, etc.; V is a bond, NH, etc. and m is an integer from 0 to 6. The metal chelating moiety comprises DOTA that chelates a radionuclide/metal including a radionuclide for PET, SPECT, such as 99mTc, 64Cu, 67Cu, etc.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the linker of Dvořáková et al. to bind the FAP-specific inhibitors of Jansen I to a DOTA chelator via the linker for the advantage of radioimaging and/or radiotherapy of tumors as Dvořáková et al. examined various PEG linkers to determine the most effective for site specific FAP targeting for tumor imaging.
Applicant asserts that -C1-6alkyl and the -O-C1-6 alkyl are among a wide variety of alternative functional groups that may optionally be attached to the heterocyclic group of generic structure of the FAP inhibitor compounds in Jansen I. Furthermore, among 43 representative compounds disclosed in Jansen I and 39 representative compounds in Jansen II, only a single compound with a halogenated -C1-6alkyl or -O-C1-6alkyl is disclosed. See Pomper Affidavit, Para. 24. Thus, the prior art provides no motivation or indication to select -C1-6alkyl or the -O-C1-6alkyl from a large group of functional groups as a substituent group on the FAP inhibitors disclosed in Jansen I or Jansen II. In fact, in most of the halogenated compounds disclosed in Jansen I and Jansen II, the halogen is directly attached to the heterocyclic group, instead of via a -C1-6alkyl or the -O-C1-6alkyl.
The Examiner asserts that the declaration is not directed to the instant application but labeled for Application No. 18/354,282.
The declaration addresses the 35 U.S.C. 102 rejection of claim 29 over Dvořáková et al. and the 35 U.S.C. 103 rejection of claim 29 over Jansen et al. (US2014/0357650A1) in view of Zimmerman et al. (US2010/0098633A1) and Jensen et al. (ACS Med. Chem. Lett. 2013, 14, 491-496) that was used in the office action of Application No. 18/354,282.
The Examiner asserts that the quinoline moiety of the compound
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of Jansen I may be substituted with halogenated -C1-6alkyl, -O-C1-6alkyl substituents wherein the -C1-6alkyl, -O-C1-6alkyl groups encompass the linkers of the instant claims that bind a halogen to the
quinoline moiety of
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. Therefore, Jansen I envisioned multiple halogenated -C1-6alkyl, -O-C1-6alkyl substituents with varying alkyl chain length and each embodiment does not need to be exemplified.
Further, the instant claims have been amended to cancel the radiohalogens.
The Examiner’s assertions with regards to the references Dvořáková et al. and Jensen II are stated above.
Applicant asserts that one of ordinary skill in the art would not select the single FAP inhibitor substituted with the halogenated -C1-6alkyl or the -O-C1-6alkyl disclosed in Jansen I and Jansen II as a starting point or a lead compound to modify, because this compound has mediocre bioactivities compared with the other compounds disclosed in the prior art. In particular, many other FAP inhibitors of Jansen I and Jansen II have more favorable affinity and specificity properties than Example 11 of
Jansen I or Compound 28 of Jansen II, which is substituted with a trifluoromethoxy group. See Pomper Affidavit, Para. 26. For example, compound 11 of Jansen I with the trifluoromethoxy substitution has a IC50 of 0.012 µm and a selectivity index of 59, which do not compare favorably to a number of compounds including compound Example 15, which has an IC50 of 0.0062 µm and a selectivity index of 193.
The Examiner asserts that the declaration is not directed to the instant application but labeled for Application No. 18/354,282.
The declaration addresses the 35 U.S.C. 102 rejection of claim 29 over Dvořáková et al. and the 35 U.S.C. 103 rejection of claim 29 over Jansen et al. (US2014/0357650A1) in view of Zimmerman et al. (US2010/0098633A1) and Jensen et al. (ACS Med. Chem. Lett. 2013, 14, 491-496) that was used in the office action of Application No. 18/354,282.
The Examiner asserts that the quinoline moiety of the compound
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of Jansen I may be substituted with halogenated -C1-6alkyl, -O-C1-6alkyl substituents wherein the -C1-6alkyl, -O-C1-6alkyl groups encompass the linkers of the instant claims that bind a halogen to the
quinoline moiety of
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. Therefore, Jansen I envisioned multiple halogenated -C1-6alkyl, -O-C1-6alkyl substituents with varying alkyl chain length and each embodiment does not need to be exemplified.
Further, the instant claims have been amended to cancel the radiohalogens.
The Examiner’s assertions with regards to the references Dvořáková et al. and Jensen II are stated above.
Applicant asserts that the Office Action appears to correlate the substitution of a -C1-6alkyl or -O-C1-6alkyl on the quinoline ring of the FAP inhibitors as a “linker” to the fact the quinoline-containing FAP inhibitors have 60 times more FAP-affinity than N-(1-naphthaoyl) FAP inhibitors. Applicant points out that Jansen II merely discloses that quinoline-containing FAP inhibitors have a 60 times higher FAP-affinity than the N-(1-naphthaoyl) FAP inhibitors. See Pomper Affidavit, Para. 27. Jansen II does not suggest that substitution of the quinoline ring of the quinoline-containing FAP inhibitors would, let alone could, improve the FAP affinity or selectivity of the FAP inhibitors. See Pomper Affidavit, Para. 27.
The Examiner did not assert that the substitution of a -C1-6alkyl or -O-C1-6alkyl on the quinoline ring of the FAP inhibitors as a “linker” to the fact the quinoline-containing FAP inhibitors have 60 times more FAP-affinity than N-(1-naphthaoyl) FAP inhibitors. The Examiner stated that the radiohalogenated quinoline FAP inhibitor for imaging FAP provides 60 times more FAP-affinity than the naphthoyl derivative. Therefore, the quinoline-containing FAP inhibitors provides a more advantageous FAP-affinity than the naphthoyl-containing FAP inhibitors.
Applicant asserts that the FAP imaging agents of Zimmerman most likely would not function well because of the poor specificity associated with the compounds of Zimmerman. See Pomper Affidavit, Para. 32-35. In particular, a representative compound disclosed in Zimmerman, namely MIP-1232, was extensively investigated as a potential medical imaging agent for atherosclerotic plaque, and was determined as not suitable for the application. See Pomper Affidavit, Para. 32-35.
The Examiner asserts that the declaration is not directed to the instant application but labeled for Application No. 18/354,282.
The declaration addresses the 35 U.S.C. 102 rejection of claim 29 over Dvořáková et al. and the 35 U.S.C. 103 rejection of claim 29 over Jansen et al. (US2014/0357650A1) in view of Zimmerman et al. (US2010/0098633A1) and Jensen et al. (ACS Med. Chem. Lett. 2013, 14, 491-496) that was used in the office action of Application No. 18/354,282.
The reference of Zimmerman was not explicitly used to teach of FAP imaging with the compounds having the structure
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but was used to teach that bonding a metal-chelate to FAP inhibitors allows for the advantage of imaging via PET, SPECT, etc.
Applicant asserts that Meletta pronounced binding of [125I]MIP-1232 to carotid plaques was observed, but did not observe any difference in average specific binding between stable and vulnerable plaques and between plaques and normal arteries. See Pomper Affidavit, Para. 34. Based on these data, Meletta could not conclude on the selectivity of [125I]MIP-1232 for FAP. Accordingly, because of the low specificity MIP-1232 displayed in the investigation, Meletta concluded that MIP-1232 was not suitable for medical imaging for the medical condition. The unexpected specificity/selectivity of XY-FAP-01 and XY-FAP-02 imaging agents and compounds falling under the scope of the pending claims of the current application are generally several orders of magnitude higher than that of other small molecule FAP inhibitors. See Pomper Affidavit, Para. 42. MIP-1232, which is a representative compound of Zimmerman, has a PREP/FAP ratio of 32, compared to the lowest value of 779 and highest value of 1,418,440 for representative compounds of the pending claims. It is also notable that the other reference compounds which share the same FAP moieties but do not have a linker also have a significantly lower PREP/FAP ratio in the range from 3 to 403. The difference in specificity between the reference compound of the prior art and the compounds of the pending claims are surprising and unexpected.
The Examiner asserts that the declaration is not directed to the instant application but labeled for Application No. 18/354,282.
The declaration addresses the 35 U.S.C. 102 rejection of claim 29 over Dvořáková et al. and the 35 U.S.C. 103 rejection of claim 29 over Jansen et al. (US2014/0357650A1) in view of Zimmerman et al. (US2010/0098633A1) and Jensen et al. (ACS Med. Chem. Lett. 2013, 14, 491-496) that was used in the office action of Application No. 18/354,282.
Therefore, the surprising and unexpected results address the incorrect Application No. 18/354,282 and not the instant application.
Further, the instant claims have been amended to cancel the radiohalogens.
The Examiner’s assertions with regards to the references Dvořáková et al. and Jensen II are stated above.
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 28-32 and 35-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42-46,53-62 and 64-67 of copending Application No. 18/553,092 as stated in the office action mailed 6/5/25.
Applicant request that this rejection be held in abeyance until the claims are otherwise found allowable.
The rejection is maintained and not held in abeyance.
Conclusion
No claims are allowed at this time.
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 MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MELISSA J PERREIRA/ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618