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 .
Acknowledgement of Receipt
Applicant’s Response, filed 11/12/2025, in reply to the Office Action mailed 8/12/2025, is acknowledged and has been entered. Claim 1 has been amended. Claims 1, 41-69 and 71-78 are pending, of which claims 46-48, 50, 57-67 and 71-78
are withdrawn from consideration at this time as being drawn to a non-elected invention. Claims 1, 41-45, 49, 51-56 and 69 encompass the elected invention and are examined herein on the merits for patentability.
Response to Arguments
Applicant’s arguments have been fully considered. Any rejection not reiterated herein has been withdrawn as being overcome by claim amendment. The rejection under 35 U.S.C. 103 over Low (WO 20/081522) is withdrawn in view of Applicant’s showing that the Low reference is not applicable as prior art. The Examiner’s response to Applicant’s arguments is incorporated below.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 41-45, 49, 51-56 and 69 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites a compound represented by a structure of formula (X): Am-L-B (X) wherein A is a radical of a fibroblast activation protein alpha (FAPa) ligand comprising a structure of formula (X-A):
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246
362
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, etc.
It is noted that as a result of amendment, a structure according to formula X-A does not appear in the claim, rather X-B as shown in line 6 of claim 1. As such, the metes and bounds of the claims are not clearly set forth and the scope of the invention cannot be distinctly ascertained.
The dependent claims fall therewith.
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 1, 41-45, 49, 51-56, 68, and 69 were provisionally rejected on the ground of non- statutory double patenting as being unpatentable over the claims of co-pending Application No. 17/995,806 (reference application), for reasons set forth in the previous Office Action.
Claims 1, 41-45, 49, 51-56, 68, and 69 were provisionally rejected on the ground of non- statutory double patenting as being unpatentable over the claims of co-pending Application No. 17/759,814 (reference application), for reasons set forth in the previous Office Action.
Claims 1, 41-45, 49, 51-56, 68, and 69 were provisionally rejected on the ground of non- statutory double patenting as being unpatentable over the claims of co-pending Application No. 18/550,964 (reference application), for reasons set forth in the previous Office Action.
Claims 1, 41-45, 49, 51-56, 68, and 69 were provisionally rejected on the ground of non- statutory double patenting as being unpatentable over the claims of co-pending Application No. 18/660,867 (reference application), for reasons set forth in the previous Office Action.
Response to arguments
Applicant requests that the Office hold the subject obviousness-type double patenting rejections in abeyance until such time as the claims at issue are deemed otherwise allowable.
Applicant’s arguments with regard to the ‘806, ‘814, ‘964 and ‘867 Applications have been fully considered. The rejections are maintained at this time as a terminal disclaimer has not been received.
Claims 1, 41-45, 49, 51-56, 68 and 69 were rejected on the ground of non-statutory double patenting as being unpatentable over claims 2+ of U.S. Patent No. 11,426,472, in view of Jiaang (US 2010/0234431), for reasons set forth in the previous Office Action.
Claims 1, 41-45, 49, 51-56, 68 and 69 were rejected on the ground of non-statutory double patenting as being unpatentable over claims 2+ of U.S. Patent No. 11,890,357 in view of Jiaang, for reasons set forth in the previous Office Action.
Response to arguments
Applicant argues that none of the claims of the '472 and ‘357 patents recite a radical of FAPα ligand, much less a FAPα ligand of the structure as claimed. Instead, the claims of the '472 and ‘357 patents recite a particular chemical formula of a PI3K inhibitor conjugated to "a FAP binding ligand" generally. Applicant asserts that Jiaang cannot and does not cure the deficiencies in the claims of the '472 and ‘357 patents and that Jiaang fails to teach or suggest a compound with a formula as claimed that includes a radical of a FAPα ligand linked to a moiety B that is a radical of an optical dye, a photodynamic therapeutic agent, a radio- imaging agent, a radiotherapeutic agent, a chemotherapeutic agent, an antifibrotic agent, or an anticancer agent. Applicant asserts that Jiaang fails to teach or suggest the claimed FAPα ligand having the group J comprising C(R)¹₂, wherein each R¹ is independently H or alkyl, or both R' are taken together to form OXO. Even if a skilled artisan were to modify the '472 patent claims according to Jiaang, they would not arrive at the subject matter falling within the scope of amended claim 1 since Jiaang is silent as to how their FAP inhibitors could be linked to a B as claimed.
Applicant’s arguments have been fully considered but are not found to be persuasive. The claims of the '472 and ‘357 patents claim 2 are generic to the identity of the FAP targeting ligand, as such it would have been obvious to provide a known FAP targeting ligand. The PI-3 kinase inhibitor in the ‘472 and ‘357 patents has the same structure fragment as that of claims 53+ of the instant claims. See also claim 3 of the ‘357 patent showing oxo or CH2 coupling equivalent to the stated J position for linking to the rest of the conjugate. Applicant’s arguments have been fully considered but the rejections are maintained.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claim(s) 1, 41-45, 49, 51-52, 68 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Low et al. (WO 2018/111989) in view of Jiaang et al. (US 2010/0234431), for reasons set forth in the previous Office Action.
Claims 1, 41-45, 49, 51-56, 68 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Low et al. (WO 2018/111989) in view of Jiaang et al. (US 2010/0234431), in further view of Petter et al. (WO 2011/082285), for reasons set forth in the previous Office Action.
Response to arguments
Applicant argues that there is nothing in Low Il or Jiaang that would motivate those of skill in the art to replace Low II's ligands with the Jiaang ligand. After all, Low II's compounds already exhibited excellent activity in the nanomolar range. For example, Tc labeled JFL-L3 displayed low nanomolar binding (KD) of 10.5 nM, citing Low II at paragraph [00309]. Applicant asserts that there is no motivation to replace Low II's ligands from the outset. Beyond the structural differences between the claimed compounds and Jiaang's, there are also functional differences stemming from those structural differences that would dissuade those of skill in the art from modifying the targeting portion of Low II's compounds with Jiaang's compounds, which goes toward establishing a lack of a reasonable expectation of success. Applicant notes that Jiaang discloses compounds that are therapeutically useful in their own right and not as targeting compounds for the delivery of other therapeutic or diagnostic agents. In addition, Jiaang's compounds have IC₅₀ values in the micromolar range, citing Jiaang at paragraph [0081]. Such IC₅₀ values are high (less potent) and those of skill in the art would expect erosion of the nanomolar KD values of the Low II compounds. This alone would not only dissuade the skilled artisan form the switch that the Patent Office suggests but would also remove a reasonable expectation of succeeding at developing more potent compounds at least because, based on the data in Jiaang, the binding constant of the resulting compounds would be inferior.
Applicant’s arguments have been fully considered but are not found to be persuasive. It is respectfully submitted that, with regard to IC50 values, Jiaang states that compounds 1-9, 12, 13, 16-18, and 20 had IC50 values lower than 1 µM. It is respectfully submitted that less than one micromolar is on the order of nanomolar as taught by Low, as such it is considered that the FAP targeting ligands are functionally equivalent, and it would have been obvious to substitute one FAP targeting ligand for another.
Applicant further argues that Petter cannot and does not remedy the defects of Low II and Jiaang. Just because Petter might describe a PI3K inhibitor conjugated to a lysine residue of PI3Kβ or PI3Kγ protein scaffold, and Applicant is not admitting as much, it does not mean that those of skill in the art would be motivated to conjugate a PI3K inhibitor to a FAP ligand via a linker as claimed with the reasonable expectation of obtaining a biologically active compound. There simply is no reason to do so with a reasonable expectation of success. The only reason to do so would be based on impermissible hindsight.
Applicant’s arguments have been fully considered but are not found to be persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Low teaches PI3K inhibitor as a chemotherapeutic agent but does not specifically recite the structure. One of ordinary skill would have been motivated to select a PI3K inhibitor of Formula O for conjugation, with a reasonable expectation of success, because Netter teaches the compounds to be a Pi3K inhibitor which is linked to a targeting ligand.
Conclusion
No claims are allowed at this time.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 LEAH H SCHLIENTZ whose telephone number is (571)272-9928. The examiner can normally be reached Monday-Friday, 8:30am - 12:30pm EST.
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/LHS/
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618