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 .
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.
This office action is a response to applicant’s election submitted May 12, 2026, claims filed October 6, 2023 wherein claims 3-4, 6, 11, 17, 21, 22, 27, 29, 35, 39, 41-43, 48-49, 52, 54-55, 57, 62, 68, 70, 72-73, 78, 80, 86, 89-90, 92, 99, 103-105, 107 were preliminarily amended, and claims 5, 7-10, 12-16, 18-20, 23-26, 28, 31-34, 37, 38, 40, 44-47, 51, 53, 56, 58-61, 63-67, 69, 71, 74-77, 79, 82-85, 88, 91, 93-98, 100-102, 108-126 were canceled and are examined herein. This application claims benefit of provisional application 63/355,975 filed 06/27/2022.
Claims 1-4, 6, 11, 17, 21, 22, 27, 29, 30, 35, 36, 39, 41-43, 48-50, 52, 54, 55, 57, 62, 68, 70, 72, 73, 78, 80, 81, 86, 87, 89, 90, 92, 99 and 103-107 are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I and claimed compound 101, which has the following structure:
PNG
media_image1.png
348
420
media_image1.png
Greyscale
in the reply filed on May 12, 2026 is acknowledged. The compound includes the chiral variant recited by instant claim 41 (compound 107). The elected species read on claims 1-4, 6, 17, 21, 22, 27, 35, 36, 39, 41, 48-50, 52, 54, 55, 57, 68, 70, 72, 73, 78, 86, 87, 89, 90, 92, and 99. In order to facilitate compact prosecution, the search was expanded to the additional species
PNG
media_image2.png
400
424
media_image2.png
Greyscale
110 (encompasses achiral variant 104) which is encompassed by claims 1-4, 6, 17, 21, 22, 27, 35, 36, 39, 41, 48-50, 52, 54, 55, 57, 68, 70, 72, 73, 78, 86, 87, 89, 90, 92, and 99.
Claims 103-107 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 12, 2026.
Claims 11, 29-30, 42-43, 62, 80, 81 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 12, 2026.
Thus claims 1-4, 6, 17, 21-22, 27, 35-36, 39, 41, 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89, 90, 92, and 99 read on the elected species and are examined herein.
Claim Objections
Claims 49-50, 87, 89, 92, and 99 are objected to because of the following informalities:
In claims 49-50, the phrase “a residue of a second compound” should read “a residue of the second compound”.
Claim 87 has a forward slash (\) after the period.
In claim 89 the acronym EDA should be defined.
In claims 90 and 92 The phrase “the compound is selected from” should read “the conjugate is selected from” for consistency.
In claim 99 the phrase “comprising the compound” should read “comprising the conjugate”.
Appropriate correction is required.
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 1-4, 6, 17, 21-22, 27, 35-36, 39, 41, 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89-90, 92, and 99 are rejected under 35 U.S.C. 103 as being unpatentable over Burke (Mol. Cancer Ther., 2017, IDS filed October 6, 2023) in view of Maderna (WO 2020/252043, cited on PTO-892) and Viricel (WO 2022/207699, cited on PTO-892).
Regarding claims 1-4, 6, 17, 21-22, 27, 35-36, 39, 41, 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89-90, 92, and 99: Burke teaches antibody-drug conjugates (ADC) with incorporation of PEG polymer side chains in beta-glucuronidase-cleavable monomethylauristatin E (MMAE) linker to provide homogeneous DAR 8 conjugates with decreased plasma clearance and increased antitumor activity in xenograft models relative to a non-PEGylated control (abstract). A lead PEGylated glucuronide-MMAE linker was identified incorporating a self-stabilizing maleimide and a PEG12 side chain emerged from these efforts, enabling highly potent, homogeneous DAR 8 conjugates and is under consideration for future ADC programs (abstract). Burke teaches the optimization of the drug linker in ADCs is a routine practice in the art to modify clearance and uptake properties (i.e. result effective, abstract, pg. 116, col. 2, paras. 2-3). Burke teaches the following compounds
PNG
media_image3.png
168
428
media_image3.png
Greyscale
wherein m can be 2, 4, 8, 12, or 24, and n = 1 (pg. 119, figure 2). Burke additionally teaches modifications the maleimidocaproyl group as demonstrated in figure 1
PNG
media_image4.png
207
305
media_image4.png
Greyscale
(pg. 117). Burke teaches the glucuronic linker system represents a hydrophilic alternative to val-cit dipeptide (pg. 117, col. 1, para. 1). Burke teaches the maleimide group is to be conjugated to reducible native antibody cysteine disulfides (i.e. residue of an antibody, pg. 116, col. 2, para. 2, pg. 117, figure 1). Burke teaches glucuronide linker systems has been used to mitigate aggregation issues with lipophilic payloads like camptothecins (pg. 117, col. 1, para. 1). Burke tests the ADCs in PBS solution (i.e. aqueous solution, composition in a carrier, pg. 118, col. 2, para. 2).
The compound of Burke differs from the elected compound 101 in the active drug (MMAE vs exatecan), the conjugating group (maleimide vs cyclooctyne), and the number of carbons joining the conjugating group and the PEG linker (i.e. PEG-connecting group,
PNG
media_image5.png
99
180
media_image5.png
Greyscale
vs
PNG
media_image6.png
73
215
media_image6.png
Greyscale
). The compound of Burke differs from the elected compound 110 in the active drug (MMAE vs exatecan) and the conjugating group (maleimide vs cyclooctyne).
Maderna teaches 5H-Pyrrolo[3,2-d]pyrimidine-2,4-diamino compounds, and/or antibody conjugates thereof; and pharmaceutical compositions comprising the compounds and/or conjugates; methods of producing the compounds and/or conjugates; and methods of using the compounds, conjugates and compositions for therapy (pg. 1, para. 0001). Maderna teaches the following antibody drug conjugate
PNG
media_image7.png
261
423
media_image7.png
Greyscale
(pg. 108, third compound down). Maderna teaches an additional compound which incorporates a PEGylated side chain to the conjugating group
PNG
media_image8.png
251
373
media_image8.png
Greyscale
wherein a methyl amide serves as the branching point (pg. 191, para. 00520). Maderna generally teaches the eliminator group can differ in structure
PNG
media_image9.png
313
148
media_image9.png
Greyscale
(pg. 48, para. 00161). Maderna generally teaches the following conjugating groups which facilitate conjugation of the payloads to an antibody include
PNG
media_image10.png
125
87
media_image10.png
Greyscale
and
PNG
media_image11.png
82
51
media_image11.png
Greyscale
(pg. 54, para. 00181). Maderna teaches conjugation can be formed through a formed through a strain-promoted [3+2] alkyne-azide cycloaddition (SP AAC) reaction:
PNG
media_image12.png
111
220
media_image12.png
Greyscale
(pgs. 54-55, para. 00183).
Additionally, Viricel teaches compounds that are ligand-drug conjugates which when bound to an antibody or antibody fragment are known as antibody-drug-conjugates (abstract, pg. 1, lines 15-25). Viricel teaches the ligand units and drug units are joined via a synthetic linker, which may comprise spacers, connectors, and enzyme-sensitive cleavable moieties (pg. 1, lines 16-20). Said linker may orthogonally bear any moiety that can improve the LDC performance, such as storage stability, plasmatic stability or pharmacokinetics properties (pg. 1, lines 15-22). Viricel teaches MMAE and exatecan are known alternative drug compounds for antibody drug conjugate systems
PNG
media_image13.png
265
313
media_image13.png
Greyscale
(pg. 43, scheme 1.2.1, pg. 45, scheme 1.2.2).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the compound of Burke by modifying the PEG-connecting group length to a single carbon and substituting the conjugating group with the cyclooctyne moiety as taught by Maderna as well as substituting MMAE with exatecan as taught by Viricel and arrive at elected compound 101. It would also have been prima facie obvious to a person of ordinary skill in the art to modify the compound of Burke by substituting the conjugating group with the cyclooctyne moiety as taught by Maderna as well as substituting MMAE with exatecan as taught by Viricel and arrive at elected compound 110. A person of ordinary skill in the art would have had the motivation to modify connector length with a reasonable expectation of success as modification of linker lengths is a known result effective variable, and connector lengths of one carbon are taught in the art of ADCs (See MPEP 2144.05 (II)). A person of ordinary skill in the art would have had the motivation to substitute MMAE with exatecan with a reasonable expectation of success as the art demonstrates camptothecins are commonly used in ADCs, and exatecan is a known alternative to MMAE. Wherein both compounds are known drug molecules to be incorporated into ADCs, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)).
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 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89, 90, 92, and 99 rejected on the ground of nonstatutory double patenting as being unpatentable over the claim of U.S. Patent No. 12,144,869 (cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The patented claims teach the following antibody conjugate
PNG
media_image14.png
285
502
media_image14.png
Greyscale
wherein n2 is 1 (claim 10). The patented claims teach a pharmaceutical composition comprising the conjugate and a pharmaceutically acceptable carrier (claim 20).
Claims 1-4, 6, 17, 21-22, 27, 35-36, 39, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claim of U.S. Patent No. 12,144,869 (cited on PTO-892) as applied to claims 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89, 90, 92, and 99 above in view of Maderna (WO 2020/252043, cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
As discussed above, the patented claims teach the antibody conjugate described above.
They do not explicitly teach the unconjugated compound as recited by instant claims 1-4, 6, 17, 21-22, 27, 35-36, 39, and 41.
However, Maderna teaches 5H-Pyrrolo[3,2-d]pyrimidine-2,4-diamino compounds, and/or antibody conjugates thereof; and pharmaceutical compositions comprising the compounds and/or conjugates; methods of producing the compounds and/or conjugates; and methods of using the compounds, conjugates and compositions for therapy (pg. 1, para. 0001). Maderna teaches the following antibody drug conjugate
PNG
media_image7.png
261
423
media_image7.png
Greyscale
(pg. 108, third compound down). Maderna teaches an additional compound which incorporates a PEGylated side chain to the conjugating group
PNG
media_image8.png
251
373
media_image8.png
Greyscale
wherein a methyl amide serves as the branching point (pg. 191, para. 00520). Maderna generally teaches the eliminator group can differ in structure
PNG
media_image9.png
313
148
media_image9.png
Greyscale
(pg. 48, para. 00161). Maderna generally teaches the following conjugating groups which facilitate conjugation of the payloads to an antibody include
PNG
media_image10.png
125
87
media_image10.png
Greyscale
and
PNG
media_image11.png
82
51
media_image11.png
Greyscale
(pg. 54, para. 00181). Maderna teaches conjugation can be formed through a formed through a strain-promoted [3+2] alkyne-azide cycloaddition (SP AAC) reaction:
PNG
media_image12.png
111
220
media_image12.png
Greyscale
(pgs. 54-55, para. 00183).
Taken together, it would have been prima facie obvious to modify the conjugate of the patented claims to retro synthetically arrive at the unconjugated compound as taught by Maderna. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to further conjugate with other antibodies and the patented claims teach the compound to be conjugated with antibodies.
Claims 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89, 90, 92, and 99 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 12,226,490 (cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The patented claims teach the following antibody conjugate
PNG
media_image14.png
285
502
media_image14.png
Greyscale
wherein n2 is 1 (claim 47). The patented claims teach a pharmaceutical composition comprising the conjugate and a pharmaceutically acceptable carrier (claim 144).
Claims 1-4, 6, 17, 21-22, 27, 35-36, 39, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 12,226,490 (cited on PTO-892) as applied to claims 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89, 90, 92, and 99 above in view of Maderna (WO 2020/252043, cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
As discussed above, the patented claims teach the antibody conjugate described above.
They do not explicitly teach the unconjugated compound as recited by instant claims 1-4, 6, 17, 21-22, 27, 35-36, 39, and 41.
However, Maderna teaches 5H-Pyrrolo[3,2-d]pyrimidine-2,4-diamino compounds, and/or antibody conjugates thereof; and pharmaceutical compositions comprising the compounds and/or conjugates; methods of producing the compounds and/or conjugates; and methods of using the compounds, conjugates and compositions for therapy (pg. 1, para. 0001). Maderna teaches the following antibody drug conjugate
PNG
media_image7.png
261
423
media_image7.png
Greyscale
(pg. 108, third compound down). Maderna teaches an additional compound which incorporates a PEGylated side chain to the conjugating group
PNG
media_image8.png
251
373
media_image8.png
Greyscale
wherein a methyl amide serves as the branching point (pg. 191, para. 00520). Maderna generally teaches the eliminator group can differ in structure
PNG
media_image9.png
313
148
media_image9.png
Greyscale
(pg. 48, para. 00161). Maderna generally teaches the following conjugating groups which facilitate conjugation of the payloads to an antibody include
PNG
media_image10.png
125
87
media_image10.png
Greyscale
and
PNG
media_image11.png
82
51
media_image11.png
Greyscale
(pg. 54, para. 00181). Maderna teaches conjugation can be formed through a formed through a strain-promoted [3+2] alkyne-azide cycloaddition (SP AAC) reaction:
PNG
media_image12.png
111
220
media_image12.png
Greyscale
(pgs. 54-55, para. 00183).
Taken together, it would have been prima facie obvious to modify the conjugate of the patented claims to retro synthetically arrive at the unconjugated compound as taught by Maderna. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to further conjugate with other antibodies and the patented claims teach the compound to be conjugated with antibodies.
Claims 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89, 90, 92, and 99 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/824,772 (US 20250018054, cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending claim teaches the following antibody conjugate wherein n2 can be 1
PNG
media_image15.png
374
543
media_image15.png
Greyscale
(claim 10). The copending claims teach a pharmaceutical composition comprising an antibody conjugate (claim 28).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-4, 6, 17, 21-22, 27, 35-36, 39, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/824,772 (US 2025/0018054, cited on PTO-892) as applied to claims 48-50, 52, 54-55, 57, 68, 70, 72-73, 78, 86-87, 89, 90, 92, and 99 above in view of Maderna (WO 2020/252043, cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
As discussed above, the copending claims teach the antibody conjugate described above.
They do not explicitly teach the unconjugated compound as recited by instant claims 1-4, 6, 17, 21-22, 27, 35-36, 39, and 41.
However, Maderna teaches 5H-Pyrrolo[3,2-d]pyrimidine-2,4-diamino compounds, and/or antibody conjugates thereof; and pharmaceutical compositions comprising the compounds and/or conjugates; methods of producing the compounds and/or conjugates; and methods of using the compounds, conjugates and compositions for therapy (pg. 1, para. 0001). Maderna teaches the following antibody drug conjugate
PNG
media_image7.png
261
423
media_image7.png
Greyscale
(pg. 108, third compound down). Maderna teaches an additional compound which incorporates a PEGylated side chain to the conjugating group
PNG
media_image8.png
251
373
media_image8.png
Greyscale
wherein a methyl amide serves as the branching point (pg. 191, para. 00520). Maderna generally teaches the eliminator group can differ in structure
PNG
media_image9.png
313
148
media_image9.png
Greyscale
(pg. 48, para. 00161). Maderna generally teaches the following conjugating groups which facilitate conjugation of the payloads to an antibody include
PNG
media_image10.png
125
87
media_image10.png
Greyscale
and
PNG
media_image11.png
82
51
media_image11.png
Greyscale
(pg. 54, para. 00181). Maderna teaches conjugation can be formed through a formed through a strain-promoted [3+2] alkyne-azide cycloaddition (SP AAC) reaction:
PNG
media_image12.png
111
220
media_image12.png
Greyscale
(pgs. 54-55, para. 00183).
Taken together, it would have been prima facie obvious to modify the conjugate of the copending claims to retro synthetically arrive at the unconjugated compound as taught by Maderna. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to further conjugate with other antibodies and the copending claims teach the compound to be conjugated with antibodies.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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, Scarlett Y Goon can be reached at 571-270-5241. 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.
/SAMUEL L GALSTER/Examiner, Art Unit 1693
Prosecution Insights