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 6/15/2026 has been entered. Newly amended Claims 1, 3, 8-9, 12-13, 15-17, 23, 26-29, 31, 33, 40-44, and 48 are pending in the application. Applicant’s amendments to the Claims have overcome every rejection previously set forth in the Non-Final Office Action mailed 2/13/2026.
Claims 3, 16, 28-29, 33, 40-44, and 48 remain withdrawn. Claims 1, 8-9, 12-13, 15, 17, 23, 26-27, and 31 are examined on the merits herein.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Claim Objections
Claims 1 and 23 are objected to because “a1 and a2 are an integer of 1” should instead read “a1 and a2 are each an integer of 1”.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The limitations of Claim 23 broaden those of Claim 1 upon which it depends. For example, E1 is still allowed to be a bond and E2 may still be a C1alkylene despite Claim 1 removing such groups upon amendment. All such broadening limitations of Claim 23 should be made to comport with and further limit Claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 § 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, 8-9, 12-13, 15, 17, 23, and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Damayanthi (Conjugates. J. Org. Chem. 1999, vol. 64, pp. 290-292; 6/30/2026 IDS) in view of Kim (WO2017089894) and Gregson (European Journal of Medicinal Chemistry 179 (2019) 591-607).
Damayanthi teaches “Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs)…are of considerable interest because of their potential as antitumor agents… Although some efforts to date have been directed at different modifications on the PBD ring system, no attempt has been made to link the PBD ring system with other well-established DNA groove binders such as distamycin (1) and netropsin (2)” (Page 290). In particular, Compounds 5b and 6b, wherein n=2, are shown on Page 291:
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209
662
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,
in which the following definitions of examined Formula II apply to Compound 5b: Q1, Q2, Q3, Q5, and Q7 are H; Q4 is ORm, wherein Rm is C1alkyl; Y’ is O; Q6 is absent; and
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24
101
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is as appears in Compound 23 of Claim 31:
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84
287
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. However, X’ is not Linker I of Formula IV
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164
295
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as required.
Kim teaches a pyrrolobenzodiazepine modified with a glucuronic acid derivative moiety:
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219
468
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; the linker is the same as Linker I of the elected species Compound 29:
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118
330
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(Page 199). Kim teaches the PBD component may be hydrolyzed enzymatically (Page 26 and Figures 1-2, and 10).
Gregson teaches regarding the particular glucuronic acid prodrug moiety “PBD drug-linker design has focused on the inclusion of additional tumor selective triggers and use of lower-potency PBDs. b-Glucuronidase is a well-known target for discovery prodrugs due to increased presence in tumor cells and microenvironment” (Abstract).
One of skill in the art seeking to optimize the delivery of the antitumor PBD compounds of Damayanthi, motivated by Gregson teaching glucuronidase-cleavable prodrugs are specifically used for targeting tumors with PBD therapy wherein the enzyme presence is elevated, would therefore find it obvious to select the glucuronic acid prodrug moiety of Kim and attach it to the PBD compound of Damayanthi to achieve the targeted therapy as described in Gregson. The same artisan would expect success in doing so before the effective filing date of the instant claims because the attachment point of the prodrug moiety in Kim and the instant claims is at the same nitrogen atom of the PBD core and all three references are directed to anti-proliferative therapy.
Conclusion
No claim is allowable. Claim 31 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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