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 71-72,76-77,80-84,88-89 and 92-93 are pending in the application. Claims 73-75,78,79,85-87,90 and 91 are cancelled in the amendment filed 11/24/25.
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 12/3/25.
Drawings
The petition to accept colored drawings was accepted on 6/17/25.
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 71-72,76-77,80-84,88-89 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 6/2/25.
The Applicant asserts that the instant Application has the earlier term filing date with respect to Application No. 18/553,092. Applicant request withdrawal of the nonstatutory double patenting rejection at this time as they believe the claims are in condition for allowance.
The instant claims are not in condition for allowance at this time and therefore, the rejection is maintained.
New Grounds of Objection/Rejection
Claim Objections
Claim 76 is objected to because of the following informalities: the instant claim 76 is a duplicate of the instant claim 72. Appropriate correction is required.
Claim 88 is objected to because of the following informalities: the instant claim 88 is a duplicate of the instant claim 84. Appropriate correction is required.
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) 71-72,76-77,80-84,88-89 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.
Jansen et al. (US2014/0357650A1) discloses FAP inhibitors having the structures
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(abstract; p3, [0024]; p9, [0102]) that encompasses the FAP-α targeting moiety A of the instant claims.
The
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moiety comprises a 5 to 10-membered N-containing aromatic ring, etc., such as
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(p4, [0032]; p6, [0088]; p9, [0101]; p12, [0173]). The 4-quinolinoyl ring displays the best results with regards to FAP-affinities and reveals the pivotal importance of the nitrogen’s position (p41, [0633]) that encompasses the quinoline ring having a point of attachment to the remainder of the FAP-α targeting moiety at the 4-position of the quinolinyl ring of the instant claims.
The R1 and R2 moieties comprise H, halogen, etc. (p3, [0025]; p5, [0070-0071]; p9, [0103]).
The term halogen is generic for fluoro, etc. (p11, [0150]; p9, TABLE 2) that encompasses the fluoro of the instant claims.
The R1 and R2 comprise H and fluoro that encompass the corresponding R1x and R2x are H and
fluoro of the instant claims.
The R3 moiety comprises -CN, etc. (p4, [0026]; p5, [0072]; p9, [0104]; p14, [0194-0195]) that encompasses the corresponding R3x is -CN of the instant claims.
The R4 is H, etc. (p4, [0027]; p6, [0073]; p9, [0105]; p15, [0197]) that encompasses the corresponding R4x is H of the instant claims.
The n is 0,1,2, or 3 (p4, [0032]; p6, [0078],[0087]; p10, [0111],[0122]; p11, [0132],[0144]; p15, [0202]).
The
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moiety (n is 0) encompasses the moiety
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moiety when v = 0 of the FAP-α targeting moiety of the instant claims.
The R5-R7 are H, etc. (p4, [0028],[0038]; p6, [0074]; p9, [0106]) that encompass the
corresponding R5x-R7x are H of the instant claims.
The inhibitors may comprise stereoisomers, salts, etc. (p3, [0024]; p10, [0113]) and encompass the stereoisomers and salts of the instant claims.
Jansen et al. does not disclose a chelating group, optionally comprising a radionuclide.
Zimmerman et al. (US2010/0098633A1) discloses small radiopharmaceutical seprase inhibitors
(α-FAP) comprising a complex containing a proline moiety and a metal chelate to chelate a radionuclide (abstract; p1, [0002],[0007]).
The radiopharmaceuticals have a functionalized proline moiety structure
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adapted for radioimaging and/or radiotherapy (abstract; p1, [0008]; p6, [0087]).
The U comprises -CN, etc. (p1, [0010]; p6, [0089]).
The G comprises G is H, etc. (p1, [0011]; p6, [0090]).
The V is a bond, a group of formula
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, etc. (p1, [0012]; p6, [0091]).
The m is an integer from 0 to 6 (p1, [0018]; p6, [0096]).
The n is an integer from 0 to 6 (p1, [0017]; p6, [0095]).
The metal chelate is a chelating moiety that coordinates with a radionuclide/metal including a radionuclide for PET, SPECT, such as 99mTc, 64Cu, 67Cu, etc. (p1, [0019-0020]; p2, [0029]; p3, [0048-0049]; p6, [0098-0099]).
The chelating moiety comprises tetra-azacyclododecanetetra-acetic acid (DOTA), for example
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(p7, [0100]; p43, compounds 22,23).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to attach a DOTA derivative to the FAP inhibitors of Jansen et al. by binding a carboxyl moiety of DOTA to an amine moiety of the FAP-α targeting moiety to form an amide bond as Zimmerman et al. teaches of bonding a DOTA derivative chelating moieties, such as
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to a FAP-α targeting moiety to yield a FAP-α inhibitor. A 99mTc, 64Cu, 67Cu DOTA-substituted FAP-α targeting moiety provides the advantage of radioimaging and/or radiotherapy via PET or SPECT, with a reasonable expectation of success, as the expression of FAP-α on tumors makes it an attractive target to exploit for imaging and targeted radiotherapy Zimmerman et al. (p1, [0005]).
Jansen et al. does not disclose low molecular weight or that the linker is bound to the carbon atom 6 of the quinolinyl ring.
Pomper et al. (US2012/0009121A1) discloses targeting therapeutic compounds and imaging
agents for prostate cancer and cancer angiogenesis (p2, [0012]). The therapeutic compounds and imaging agents have low molecular weight (p2, [0012] wherein the 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 and (p1, [0008]; p2, [0012]; p44, [0242]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare low molecular weight DOTA-substituted FAP inhibitors with high affinity and selectivity for FAP to yield imaging agents and/or therapeutic agents with the advantage of increased uptake in tumors and improved cellular retention with a reasonable expectation of success.
Jansen et al. further discloses that the quinolinyl moiety may be substituted at the position 6,7,8 or 9
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(p12, [0172]; p16, [0215]).
Dvořáková et al. (J. Med. Chem. 2017, 60, 8385-8393) discloses anti-FAP iBody FAP inhibitors
comprising
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wherein R is H or F and n is 5 or 15 (Figure 2).
The anti-FAP iBody is for imaging of FAP-expressing cells (p8387, left column, first full paragraph; p8387, Use of Anti-FAP iBody 1 for detection and visualization of FAP; p8387, Application of Anti-FAP iBody 1 for imaging of FAP-expressing cells).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to examine the linker of Dvořáková et al. comprising a terminal amine for binding FAP-specific inhibitors to a metal chelating moiety for radiolabeling the FAP-α targeting moiety as FAP is a promising target for the diagnosis and treatment of cancer (Dvořáková et al. abstract). Also, Dvořáková et al. examined various PEG linkers to bind FAP-α targeting moieties for successful site specific targeting wherein Pomper et al. teaches that low molecular weight FAP inhibitors have the benefits of high affinity and selectivity for FAP and are advantageous as imaging and/or therapeutic agents due to increased uptake in tumors and improved cellular retention.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to attach the linker of Dvořáková et al. at the position 6 of the quinoline moiety
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of Jansen et al. with a reasonable expectation of success as Jansen et al. teaches that the quinolinyl moiety may be substituted at the position 6.
Jansen et al. does not disclose the linker L has the length of greater than lysine to [Symbol font/0x7E]33Å.
Dennis Wertz Chemistry - A Molecular Science (eBook) 3rd edition: Custom Labs (2014)
https://www.webassign.net/question_assets/wertzcams3/bond_lengths/manual.html discloses
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It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention 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, comprises a length of 26.19 Å when n is 5 and is greater than lysine as the length of the
linker can be calculated via the bond lengths of the table of Dennis Wertz.
Response to Arguments
Applicant asserts that the point of attachment of the FAP-α targeting moiety to the linker is through carbon atom 6 of the quinolinyl ring.
The reference of Jansen et al. teaches that the quinolinyl moiety may be substituted at the position 6,7,8 or 9
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(p12, [0172]; p16, [0215]).
Conclusion
No claims are allowed at this time.
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