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
Claims 92-100, 102, 106-109, 116-124, and 129-135 are pending.
Claims 116-124 and 129-131 remain withdrawn.
Claims 134-135 are new.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/28/2026 has been entered.
Objections and Rejections Withdrawn
The objections and rejections to claims 101, 103-105, and 110-115 are moot in view of claim cancelation.
The rejections to claim 98 under 35 USC §112(b) are withdrawn in view of claim amendment.
The rejections to claims 92-95, 97-100, and 132 under 35 USC §103 are withdrawn in view of claim amendment.
Claim Status
Applicant previously elected Group I and the drug linker:
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in the reply filed on 7/21/2025.
Claims 92-100, 102, 106-109, and 132-133 are pending for the Applicant elected species.
The Applicant elected species is free of prior art except for non-statutory double patenting issues.
The Applicant has amended the Application to remove the Examiner elected species of:
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and
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The next Examiner elected species is:
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Claims 134 and 135 contain the next Examiner elected species.
Claim Rejections – 35 USC § 112(d)
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.
Claim 102 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. Amended independent claim 92 contains two structures for T and claim 102 does not further limit T. Thus, claim 102 does not further limit parent claim 92 . 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.
Regarding the Examiner elected species of
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and instant claims 134-135.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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.
Claims 92-95, 97-100, and 132 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/092804 (Govindan SV et al. IDS reference), WO 2018/025168 (Dushin RG et al. IDS reference), Kline T et al. (Pharm Res (2015) 32:3480–3493), WO 2010/106341 (Yahioglu G et al.), and Oliveira BL et al. (Chem. Soc. Rev., 2017, 46, 4895-4950).
Govindan taught an effective method of treating cancer comprising administering a pharmaceutical composition comprising of the ADC hRS7-CL2A-SN-38 (page 89, [0232] and Fig. 2), wherein the antibody was conjugated to the CLA2A-SN-38 linker of
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(page 85 and pages 87-88 [0231]).
Govindan did not teach the species of:
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, but this is obvious in view of Dushin, Kline, Yahioglu, and Oliveira.
Dushin taught non-maleimide-based ADC linkers and linker components, their preparation, and their use in preparing ADCs more stable than corresponding maleimide-based ADCs (page 3-4, bridging paragraph). Dushin taught this improved stability will result in ADCs having improved therapeutic indices and/or other advantageous properties (page 3-4, bridging paragraph). Dushin taught antibodies conjugated to maleimide linker comprising ADCs H-(380C)-mcMMAD and H-(380C)-mcValCitPABC-Aur0101 were less stable in the presence of GSH compared to an antibody conjugated to a pyrimidylene linker comprising ADC of H-(380C)-#26 (pages 115-116, Table 3), wherein the #26 pyrimidylene comprising linker comprised a methylsulfonyl substituent attached to the pyrimidylene
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prior to antibody conjugation
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(page 71, Scheme for Compound #26). Dushin taught an ADC comprising an antibody conjugated to a pyrimidylene linker #26 was effective against cancer cells expressing the antibody target (pages 117-118, Table 4). Thus, antibody conjugation via pyrimidylene is known to be stable and effective.
Kline taught conjugation chemistries for antibody drug conjugates (Title). Kline taught Sonogashira cross coupling of a terminal alkyne to an aryl iodide is in principle a promising bioorthogonal chemistry for ADCs, since either an iodoPhe or an alkynyl amino acid could be used as the site of conjugation (page 3488, right column, second paragraph). Kline taught the Sonogashira coupling maintains the alkyne
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(Fig. 12).
Yahioglu taught site specific attachment of drug conjugates to cysteine residues on antibodies via a thiol coupling group of maleimide (page 85, lines 1-14). Yahioglu taught conjugation of a thiol coupling group to a drug via a Sonogashira coupling wherein
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for attachment of meso 5-brominated derivatives (page 85, lines 15-20).
Oliveira taught Sonogashira coupling reactions effectively connect cyclic 6 member rings with nitrogens to alkynes to produce a product of
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(page 4903, left column, first paragraph and Fig. 10)
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(Fig. 10).
Regarding instant claims 134-135, it would have been obvious for a person having ordinary skill in the art to take the effective drug linker of Govindan comprising the CL2A-SN-38 linker compound of
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– and modify it to:
Exchange the maleimide moiety which can be used for cysteine conjugation to an antibody for a methylsulfonyl substituent attached to a pyrimidylene moiety
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which can be used for cysteine conjugation to an antibody; and
Exchange the
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moiety conjugating the thiol conjugating moiety to the linker drug for
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in view of Kline, Yahioglu, and Oliveira.
This is obvious because:
1) Dushin taught antibodies conjugated to a pyrimidylene linker comprising ADC of H-(380C)-#26 was more stable in the presence of glutathione (GSH) and an ADC comprising an antibody conjugated to a pyrimidylene linker #26 was effective against cancer cells expressing the antibody target. Thus, exchange of maleimide with
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would beneficial.
2a) Kline taught conjugation chemistries useful for antibody drug conjugates included Sonogashira coupling of a terminal alkyne to an aryl iodide, wherein Sonogashira coupling maintains the alkyne.
2b) Yahioglu taught site specific attachment of drug conjugates to cysteine residues on antibodies via a thiol coupling group, wherein conjugation of a thiol coupling group to a drug is accomplished via a Sonogashira coupling.
2c) Oliveira taught Sonogashira coupling reactions effectively connect cyclic 6 member rings with nitrogens to alkynes to produce a product of
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.
There is a reasonable expectation of success because:
1) Dushin taught antibodies conjugated to a pyrimidylene linker comprising ADC of H-(380C)-#26 was more stable in the presence of glutathione (GSH) and an ADC comprising an antibody conjugated to a pyrimidylene linker #26 was effective against cancer cells expressing the antibody target. Thus, exchange of maleimide with
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would beneficial.
2a) Kline taught conjugation chemistries useful for antibody drug conjugates included Sonogashira coupling of a terminal alkyne to an aryl iodide, wherein Sonogashira coupling maintains the alkyne.
2b) Yahioglu taught site specific attachment of drug conjugates to cysteine residues on antibodies via a thiol coupling group, wherein conjugation of a thiol coupling group to a drug is accomplished via a Sonogashira coupling.
2c) Oliveira taught Sonogashira coupling reactions effectively connect cyclic 6 member rings with nitrogens to alkynes to produce a product of
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. Thus, it would be obvious with a reasonable expectation of success to exchange
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with
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to conjugate the antibody to the drug conjugate.
This would produce a linker compound of:
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which meets the claim limitations of instant claims 134-135.
Response to arguments
Applicant has amended the claims to exclude the previous Examiner’s elected species. The updated rejection is above for the next Examiner’s elected species.
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.
Regarding the Applicant elected species of
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The provisionally rejected claims 92-100, 102, 106-109, and 132-133 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, 21, and 23-26 of copending Application No. 18/558,201 are maintained. Although the claims at issue are not identical, they are not patentably distinct from each other because:
‘201 taught an antibody-drug conjugate that binds ROR1 with the formula Ab-[M-L-E-Dx] in claims 1-15, 18, and 23-26. ‘201 claim 16 taught a drug-linker of M’-L-E-D. ‘201 claim 17 taught a drug linker with the structure of the elected species of
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which anticipates the Applicant elected species in instant claims 92-100, 102, 106-109, and 132-133.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicant respectfully points out that according to MPEP Section 1490(VI)(D)(2)(a), "[i]f a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent ... ".
In response, Applicant's arguments filed 5/28/2026 have been fully considered but they are not persuasive. While the instant application has an earlier patent term filing date, there are still rejections remaining in the instant application. Thus, the rejection is maintained.
The provisionally rejected claims 92-100, 102, 106-109, and 132-133 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 11, 16, 20-21, 30, 32, 36-37, 40, 44-47, 50-52, and 72-76 of copending Application No. 18/859,078 are maintained. Although the claims at issue are not identical, they are not patentably distinct from each other because:
‘078 taught an antibody-drug conjugate that binds HER3 with the formula Ab-[M-L-E-Dx] in claims 1-2, 6, 11, 16, 20-21, 30, 32, 36, 45-47, 50, 52, and 72-76.
‘078 claims 37 and 40 taught a drug-linker of M’-L-E-D, wherein a pharmaceutical composition of the drug linker with a pharmaceutically acceptable excipient is taught in claim 51. Claim 44 taught a drug linker with the structure of the elected species of
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, which anticipates the Applicant elected species in instant claims 92-100, 102, 106-109, and 132-133.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicant respectfully points out that according to MPEP Section 1490(VI)(D)(2)(a), "[i]f a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent ... ".
In response, Applicant's arguments filed 5/28/2026 have been fully considered but they are not persuasive. While the instant application has an earlier patent term filing date, there are still rejections remaining in the instant application. Thus, the rejection is maintained.
The provisionally rejected claims 92-100, 102, 106-109, and 132-133 a on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 18/688,265 are maintained. Although the claims at issue are not identical, they are not patentably distinct from each other because:
‘265 claims 1-29 taught a method of improving the product quality of an antibody drug conjugate which includes a drug-linker in claims 3 and 16 that comprises the Applicant elected species of:
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which anticipates the Applicant elected species in instant claims 92-100, 102, 106-109, and 132-133.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicant respectfully points out that according to MPEP Section 1490(VI)(D)(2)(a), "[i]f a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent ... ".
In response, Applicant's arguments filed 5/28/2026 have been fully considered but they are not persuasive. While the instant application has an earlier patent term filing date, there are still rejections remaining in the instant application. Thus, the rejection is maintained.
Conclusion
Claims 92-100, 102, 106-109, and 132-135 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN J SKOKO III whose telephone number is (571)272-1107. The examiner can normally be reached M-F 8:30 - 5:00.
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, Julie Z Wu can be reached at (571)272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.J.S./Examiner, Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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