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 and Previous Objections/Rejections Status
Claims 71-72,77,80-84,89 and 92-93 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.
Response to Arguments
Applicant's arguments filed 6/11/26 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) 71-72,77,80-84,89 and 92-93 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), Pomper et al.
(US2012/0009121A1) and Dvořáková et al. (J. Med. Chem. 2017, 60, 8385-8393) 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 as stated in the office action mailed 12/11/25.
Applicant asserts that Jansen et al. does not disclose low molecular weight or the claimed linker bound to the 6-position of the quinolinyl ring. While Applicant recognizes that the portion of Jansen cited by the Office Action does disclose possible substitution of Jansen's quinolinyl ring at the 6, 7, 8, or 9 position, this disclosure would not have motivated a person of ordinary skill in the art ("POSA") to include a bi-functional linker bound to the 6-position of Jansen's quinolinyl ring. Rather, Jansen's quinolinyl substitution is limited to the disclosed R5,R6, and R7 substituents, including "-H, -OH, -oxo, halo, -C4alkyl, -O-C1-6alkyl, -S-C1-6alkyl, -NR8R9, -OR12, -Het2 and -Ar2; each of said C1-6alkyl being optionally substituted with from 1 to 3 substituents selected from -OH, -halo" and not a linker having a length of greater than lysine to [Symbol font/0x7E]33Å. Thus, while Jansen does disclose that the quinolinyl ring of Jansen's compounds can be substituted with certain substituents, none of Jansen's enumerated R5/R6/R7 options is, or suggests, a "linker having bi- functionalization adapted to form a chemical bond with B and A." The Office Action has not pointed to anywhere in Jansen or Dvořáková et al. that would have provided the requisite motivation to modify Jansen's compounds with a bi-functional linker at the 6-position of the quinolinyl ring.
The reference of Jansen et al. was not used to teach of a bi-functional linker bound to the 6-position of the quinolinyl ring but was used to teach of the core structure of the FAP-α targeting
moiety
PNG
media_image1.png
124
250
media_image1.png
Greyscale
comprising a 4-quinolinoyl ring
PNG
media_image2.png
98
96
media_image2.png
Greyscale
; R1
and R2 comprise H, fluoro and R3 moiety comprises -CN. The core structure of Jansen et al. is analogous to the core structure of the FAP-α targeting moiety
PNG
media_image3.png
208
282
media_image3.png
Greyscale
of the instant claims.
Jansen et al. further discloses that the quinolinyl moiety point of attachment * is at the 4-position and the quinolinyl moiety may be further substituted at the position 6,7,8 or 9
PNG
media_image4.png
114
102
media_image4.png
Greyscale
.
The FAP inhibitors of Jansen et al. are used to treat and/or prevent FAP-related disorders, such as cancer.
The reference of Dvořáková et al. was used to teach of FAP inhibitors comprising the FAP targeting moiety
PNG
media_image5.png
145
305
media_image5.png
Greyscale
having a bi-functional linker comprising a terminal amino moiety bound to the quinolinyl ring. The bi-functional linker is used to bind to a polymer backbone via an amide bond for in vivo imaging and selective drug delivery into a tumor microenvironment.
The reference of Zimmerman et al. was used to teach of FAP proline compounds bound to a
metal chelator
PNG
media_image6.png
90
282
media_image6.png
Greyscale
via an amide bond, such as the chelator
PNG
media_image7.png
218
264
media_image7.png
Greyscale
. The chelator chelates a radionuclide for radioimaging and/or radiotherapy.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the substituents at any of the 6,7,8 or 9 -positions of the quinolinyl ring of Jansen et al. for the bi-functional linker of Dvořáková et al. to bind a metal chelator via an amide bond for the advantage of site selective FAP targeting and allow for radioimaging and/or radiotherapy of cancer as FAP is a promising target for the diagnosis and treatment of cancer (Dvořáková et al. abstract).
Applicant asserts that the linker of Dvořáková et al. of the FAP-specific inhibitor is at the carbon 7 of the quinolinyl ring and is used for binding a chelating moiety for the advantage of radioimaging and/or radiotherapy." The Office Action recognizes that Dvořáková et al. linkers are attached at the 7-position of a quinolinyl ring, not the 6-position. Additionally, in stark contrast to the presently claimed low molecular weight compounds, Dvořáková et al. compounds are large molecular weight compounds that include a polymeric linker. Applicant respectfully submits that Dvořáková’s large molecular weight compounds that include a polymeric linker at a different position on a quinolinyl ring would not have motivated a POSA to make the necessary modifications to Jansen to synthesize the presently claimed
low molecular weight compounds.
The reference of Dvořáková et al. was not used to teach of low molecular weight compounds or binding of the FAP targeting moiety to the polymer via the amine moiety. Dvořáková et al. was used to teach of binding the bi-functional linker comprising a terminal amino moiety to the quinolinyl ring of the FAP-α targeting moiety as well as that stated above. The terminal amine moiety of the bi-functional linker is available for coupling with other moieties and not only to the polymer.
The reference of Jansen et al. discloses that the quinolinyl moiety point of attachment *
is at the 4-position and the quinolinyl moiety may be further substituted at the position 6,7,8 or 9
PNG
media_image4.png
114
102
media_image4.png
Greyscale
as well as that stated above.
Therefore, it would have been obvious to one of ordinary skill in the art to attach a linker to the FAP-α targeting moiety of Jansen et al. at any of the positions 6,7,8 or 9
PNG
media_image4.png
114
102
media_image4.png
Greyscale
as the core structure of the FAP-α targeting moiety is not altered.
The reference of Zimmerman et al. teaches of the chelator stated above.
It would have been predictable to one of ordinary skill in the art to bind a linker, such as the a bi-functional linker of Dvořáková et al. to the FAP-α targeting moiety of Jansen et al. in order to bind different moieties, such as the metal chelator of Zimmerman et al. via an amide linkage for the advantage of radioimaging and/or radiotherapy as the FAP-α targeting moiety will control the site specific targeting for the delivery of any bound moiety.
Applicant asserts that with respect to low molecular weight compounds, the Office Action cites
to Pomper for the proposition that "low molecular weight inhibitors show promise in pre-clinical
imaging studies, may have better access to tumors than larger antibodies, and have greater cellular retention." Applicant does not dispute that low molecular weight compounds and imaging agents were known in the art. However, this general knowledge does not supply the requisite motivation to modify Jansen's compounds in the particular manner required to arrive at the claimed compounds.
The reference of Dvořáková et al. was used to teach of binding the bi-functional linker comprising a terminal amino moiety to the quinolinyl ring of the FAP-α targeting moiety as well as that stated above. The terminal amine moiety of the bi-functional linker is available for coupling with other moieties and not only to the polymer.
The reference of Jansen et al. discloses that the quinolinyl moiety point of attachment *
is at the 4-position and the quinolinyl moiety may be further substituted at the position 6,7,8 or 9
PNG
media_image4.png
114
102
media_image4.png
Greyscale
as well as that stated above.
Therefore, it would have been obvious to one of ordinary skill in the art to attach a linker to the FAP-α targeting moiety of Jansen et al. at any of the positions 6,7,8 or 9
PNG
media_image4.png
114
102
media_image4.png
Greyscale
as the core structure of the FAP-α targeting moiety is not altered.
The reference of Zimmerman et al. teaches of the chelator stated above.
It would have been predictable to one of ordinary skill in the art to bind a linker, such as the a bi-functional linker of Dvořáková et al. to the FAP-α targeting moiety of Jansen et al. in order to bind different moieties, such as the metal chelator of Zimmerman et al. via an amide linkage for the advantage of radioimaging and/or radiotherapy as the FAP-α targeting moiety will control the site
specific targeting for the delivery of any bound moiety.
The binding of the metal chelator to the FAP-α targeting moiety of Jansen et al. via the bi-functional linker of Dvořáková et al. yields a low molecular weight compound that encompasses the low molecular weight compound of the instant claims, has the same properties and is capable of the same functions.
Applicant asserts that that Zimmerman discloses compounds that include chelating groups, this
disclosure alone does not establish the requisite motivation. "It does not suffice to simply be known. Applicant respectfully submits that the Office Action's conclusions can only be reached through hindsight. The Office Action has established, at most, that individual features of the claimed compounds may have been independently known across the five cited prior art references. The Office Action has not established why a POSA would have been motivated to modify Jansen's FAP inhibitors in the particular manner required to arrive at the claimed compounds: namely, by appending a chelator via a bi-functional linker to the 6-position of Jansen's quinolinyl ring. Jansen itself does not supply the requisite motivation, and none of the other four cited references bridge the gaps.
The reference of Zimmerman et al. was used to teach of FAP proline compounds bound to a metal chelator
PNG
media_image6.png
90
282
media_image6.png
Greyscale
via an amide bond, such as the chelator
PNG
media_image7.png
218
264
media_image7.png
Greyscale
that chelates a radionuclide for radioimaging and/or radiotherapy.
The reference of Dvořáková et al. was used to teach of binding a bi-functional linker comprising
a terminal amino moiety bound to the quinolinyl ring of the FAP-α targeting moiety as well as that stated above.
The reference of Jansen et al. discloses that the quinolinyl moiety point of attachment *
is at the 4-position and the quinolinyl moiety may be further substituted at the position 6,7,8 or 9
PNG
media_image4.png
114
102
media_image4.png
Greyscale
as well as that stated above.
Therefore, it would have been obvious to one of ordinary skill in the art to attach a linker the FAP-α targeting moiety of Jansen et al. at any of the positions 6,7,8 or 9
PNG
media_image4.png
114
102
media_image4.png
Greyscale
as the core structure of the FAP-α targeting moiety is not altered.
It would have been predictable to one of ordinary skill in the art to bind a linker, such as the a bi-functional linker of Dvořáková et al. to bind different moieties, such as the metal chelator of Zimmerman et al. to the FAP-α targeting moiety of Jansen et al. via an amide linkage for the advantage of radioimaging and/or radiotherapy as the FAP-α targeting moiety will control the site specific targeting for the delivery of any bound moiety.
The binding of the metal chelator to the FAP-α targeting moiety of Jansen et al. via the bi-functional linker of Dvořáková et al. yields a low molecular weight compound that encompasses the low molecular weight compound of the instant claims, has the same properties and is capable of the same functions.
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 71-72,77,80-84,89 and 92-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42-46,53-55,58-62 and 64-67 of copending Application No. 18/553,092 as stated in the office action mailed 12/11/25.
Applicant respectfully maintains that the instant Application has the earlier term filing date with respect to the 18/553,092 application. As Applicant believes that the claims in the instant Application are in condition for allowance and that the nonstatutory double patenting over the 18/553,092 application is the only rejection remaining in the Application, Applicant respectfully requests that the Examiner withdraw the nonstatutory double patenting rejection over the 18/553,092 application at this time.
The nonstatutory double patenting over the 18/553,092 application is not the only rejection remaining in the Application and therefore, the nonstatutory double patenting over the 18/553,092 application is maintained.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MELISSA J PERREIRA/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Prosecution Insights