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 .
DETAILED ACTION
Response to Amendment
The amendment filed 2/27/2026 has been entered. Newly amended Claims 1-21 are pending in the application.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Traversal of Restriction Requirement
Applicant requests that Claim 12 be rejoined for examination. Claim 12 is drawn to a linker which is distinct from the elected species. Therefore, the claim is properly withdrawn and reconsideration of rejoinder will occur when the claim upon which Claim 12 depends is found to be allowable.
Applicant further argues that Groups I-II are improperly restricted based on a misquoting of the examiner: “may instead be conjugated to another antibody moiety”. Examiner stated in the nonfinal action mailed 11/28/2025 “non-antibody moiety”. Based on a misreading, applicant construed the opposite meaning of what had been written in the action. On this basis, applicant’s argument is moot.
Lastly, Applicant states the examination of Groups II and III are not believed to carry an undue burden “in as much as claim 1 is believed to be free of the cited art and in condition for allowance”. Claim 1 is not free of the art or in condition for allowance. The restriction requirement is not withdrawn.
Therefore Claims 1-11, 13-14, and 20-21 are pending in the application and examined herein. Claims 12 and 15-19 remain withdrawn.
Response to Applicant’s Arguments
Regarding double patenting rejections which are both statutory (35 USC 101) and nonstatutory in nature, Applicant expresses the intent to let the copending application go abandoned after receiving a first action. However, the application in question has not received a first action or gone abandoned or been expressly abandoned by applicant. The rejections over extant copending claims will not be held in abeyance and are reissued below, amended appropriately to reflect Applicant’s amendments to the instant claims.
Applicant argues the narrower definition of L to mean a linker containing a reactive moiety (RM) “that is able to conjugate the linker-drug compound via a covalent bond to an amino acid residue…” has overcome the rejections issued over the cited art in the nonfinal action mailed 11/28/2025. Applicant’s new functional definition of L which contains an RM has been considered and new rejections are issued below, citing new compounds or reinterpreting previously cited structures.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 10-11, 13-14, and 20 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of Claims 7, 9-10, and 21-22 of copending Application No. 18725507. The term “preferably” in Application No. 18725507 is interpreted to be exemplary rather than limiting the embodiments of the claim. This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 5-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mishra (Chemistry Letters Vol.34, No.8 (2005) 1098-1099) as evidenced by Hoffman (Synthesis (1986), (7), 557-9).
Mishra teaches compound 6
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in Scheme 1 of Page 1098 in which the following definitions of examined formula (Ib-2) apply: R1 is O; R2’ and R2 are N; R3 is NH; n is 2; Q is CONH; R4 is H; X is C1alkylene; and L is the rest of the portion labeled “chelating unit” containing phosphonic acid. Applicant describes a linker as containing an RM which can be covalently bonded to an amino acid residue. The chelating unit of Mishra contains phosphonic acid moieties which are “able to conjugate the linker-drug compound” via nucleophilic members (-SH, -NH2, -OH, inter alia) of an amino acid to form a phosphonic acid analog.
The capability of a reaction between phosphonic acid and hydroxy, for example (present in Ser or Thr side chains), to yield covalently bonded products is documented in Hoffman. The reaction scheme on Page 558 evidences the ability described in the functional definition of L in the amended Claim 1. Because no explicit structural definition is provided, the Mishra compound still anticipates the genus of Formula (Ib-1) despite amendment.
Claims 1, 5, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vlahov (WO2004069159).
Vlahov teaches the following compound: Pte-Glu-Asp-Arg-Asp-Asp-Cys-OH (
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), in which the following definitions of examined formula (I) apply: R1 is O; R2’ and R2 are N; R3 is NH; R4 is H; R5 is H; R6 is H; R7 is H; W is aryl; n is 1; Q is absent; s is 0; X is C1alkylene; and L is the chain of amino acid residues containing Cys. Cys possesses a thiol which is an RM listed in Claim 21.
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.
Claims 1-2, 4-7, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Lohade (AAPS PharmSciTech, Vol. 17, No. 6, December 2016 (2015) 1298-1311).
Lohade teaches folic acid-modified cholesterol (CPF) for tumor treatment (Abstract) in Figure 3 of Page 1303:
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, in which the following definitions of formula (Ib-2) apply: R1 is O; R2’ and R2 are N; R3 is NH; n is 2; Q is CONH; R4, R5, and R6 are H; X is NH; and L is C(O)O-cholesterol. C(O) is an ester which is able to react with nucleophilic portions of an amino acid residue. Further, the C(O)O- portion is interpreted to be an “active ester” as listed in Claim 21 because the adjacent nitrogen is electronegative and bound to an electron-withdrawing aryl group, further inviting nucleophilic attack at the ester carbon. The resultant product of the attack is bound to the linker-drug via a covalent bond; the cholesterol functions as a leaving group.
Lohade does not teach a CPF homolog wherein n is 3 and Q is N(H)CO (
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vs.
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). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.). See MPEP 2144.09. One of skill in the art seeking to form an antitumor agent would find it obvious to form a close structural homolog wherein the CO and rightmost CH2 of the Lohade structure are switched or wherein the CH2 is positioned to the left of the amide to form a compound with an n of 3. One would expect success in forming the anticancer compound encompassed by the examined claims before the effective filing date thereof because Lohade teaches the use of CPF for treating cancer and “homologs are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties”.
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.
PROVISIONAL:
Claims 1-11, 13-14, and 20-21 are provisionally rejected on the grounds of anticipatory nonstatutory double patenting as being unpatentable over Claims 1-7, 9-10, and 21-22 of copending Application No. 18725507 (hereinafter referred to as Byondis).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to an antifolate linker-drug.
Both teach compounds of formula (I):
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(Claim 1 and Claim 1), wherein specific linkers are the same in dependent claims. Both teach applicant’s elected species:
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(Claim 13 and Claim 9). Both teach antifolate compounds sans linker:
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(Claim 20 and Claim 21).
Since both applications teach the overlapping formulae and the same compounds, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Byondis.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
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 extension fee 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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 7:30am - 4:30pm.
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, Kortney Klinkel can be reached on (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627