RESPONSE TO APPLICANT’S AMENDMENT
1 Applicant's amendment, filed on 05/13/2026, is acknowledged.
2. Claims 1, 8, 12 and 18-30 are pending and under examination.
3. The provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18910550 is hereby withdrawn in view of the Terminal Disclaimer filed 05/13/2026.
4. The following new ground of rejection(s) is (are) necessitated by the amendment submitted 05/13/2026.
5. 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.
5. Claims 1, 8, 12 and 18-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of US Pat. 12655199 (previously 17604735) in view of WO/2016/165762.
The claims of the `199 patent are directed to anti-human Claudin 18.2 comprising the VH of SEQ ID NO: 231 and VL of SEQ I DNO: 261 comprising the claimed CDRs (see sequence alignment below). The `735 applicant also claims a conjugate comprising the antibody attached to a cytotoxic drug (see referenced claims 5 14-17). The specification of the `199 patent discloses the coupling (i.e., physically linking) to conjugate the antibody to a detectable substance (see page 31 top ¶).
Alignment of VH of referenced/claimed SEQ ID NO: 231/41 and 65 comprising claims SEQ ID NO: 24-43-44.
Qy 1 GGSISSNYAWN--------------YIYYSGNTNYNPSLKS------------------- 27
||||||||||| ||||||||||||||||
Db 26 GGSISSNYAWNWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRVTISRDTSKNQFSLKLSS 85
Qy 28 -------------SYYGNSFIY 36
|||||||||
Db 86 VTAADTAVYYCATSYYGNSFIY 107
Alignment of VH of referenced/claimed SEQ ID NO: 261/116 and 65 comprising claims SEQ ID NO: 50-52.
Qy 1 KSSQSLLNSGNQKNYLT---------------WASTRES--------------------- 24
||||||||||||||||| |||||||
Db 24 KSSQSLLNSGNQKNYLTWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISS 83
Qy 25 -----------QNAYSFPWT 33
|||||||||
Db 84 LQAEDVAVYYCQNAYSFPWT 103
The claims of the `199 patent differs from the claimed invention only in the recitation of vc-PAB linker.
However, the `576 publication provides anti-CLDNl 8.2 antibody-drug conjugates which are effective for treating and/or preventing cancer diseases associated with cells expressing CLDN18.2. The `576 publication demonstrates the existence of anti-CLDN18.2 monoclonal antibodies that can be highly efficiently internalized upon CLDN18.2 binding on CLND18.2-expressing cells and therefore are suitable for ADC development. Furthermore, the successful conjugation of such antibodies to the drugs DM4 and MMAE using cleavable SPDB or Val-Cit (vc) linkers, respectively, is disclosed. In vitro, the antibody conjugates reduce viability of gastric and pancreatic cancer cells expressing CLDN18.2. IMAB362-vcMMAE and EMAB362-DM4 do not bind to or influence viability of CLDN18.2 negative cells. Both, the DM4 and vcMMAE conjugates exert bystander killing effects on CLDN18.2 negative cancer cells co-cultured with CLDN18.2 positive cancer cells in vitro. Furthermore, in vivo, intravenous administration of the antibody conjugates in nude mice with CLDN18.2-positive gastric or pancreatic xenograft tumors results in dose-dependent tumor growth inhibition, survival benefit and even complete regression of early and advanced tumors (see Figs. 1, 4-8, 15-17). Fig. 1B shows that use of vc-PAB linker (cathepsin cleavable linker (vc) + self-immolative spacer (PAB)).
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Those of skilled in the art would have had a reason to use the cleavable vc-PAB linker taught by the `762 publication in attaching the anti-CLDN18.2 antibody to the cytotoxic drug claimed in the `199 patent because the anti-CLDN18.2 conjugates comprising cleavable vc-PAB linker results in dose-dependent tumor growth inhibition, survival benefit and even complete regression of early and advanced tumors. Further, vc-PAB provides high stability of the toxin-conjugated antibodies (see example 3).
Applicant’s arguments, filed 05/13/2026, have been fully considered, but have not been found convincing.
Applicant submits that the claims has been amended to recite the linker MC-vc-PAB linking the anti-Claudin 18.2 antibody to a cytotoxic agent that showed significant inhibitory activity on tumor growth.
Further, Applicant argues that the linker linking an antibody to a cytotoxic agent in an antibody drug conjugate (ADC) is not an inert spacer, but can determine and significantly alter the physical properties of the ADC. Applicant cites Sheyi et al (Pharmaceutics 14(2):396(2022):
The linker is an essential component in ADC design. It connects the antibody
to the cytotoxic payload via covalent conjugation. The key requirement of a
linker is that it must ensure chemical stability of the ADC within the bloodstream
(i.e., have a half-life 10 times longer than the ADC) and allow for rapid release of
the payload at the target site after internalization. In addition to the above
parameters that minimize premature drug release, hydro/lipophilicity, a property
that enhances the coupling of payloads and reduces immunogenicity, is also a key
aspect of linkers.
Applicant submits that in view of the amendments to the claims, and the knowledge in the art that much experimentation and creative work may be required to select a linker that will yield an ADC exhibiting good biological activity, the amended claims of the instant application are patentably distinct from the asserted claims of the '735 application.
This is not found persuasive because those of skilled in the art would have had a reason to use the cleavable vc-PAB linker taught by the `762 publication in attaching the anti-CLDN18.2 antibody to the cytotoxic drug claimed in the `199 patent because the anti-CLDN18.2 conjugates comprising cleavable vc-PAB linker results in dose-dependent tumor growth inhibition, survival benefit and even complete regression of early and advanced tumors. Further, vc-PAB provides high stability of the toxin-conjugated antibodies.
6. Claims 1, 8, 12 and 18-30 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-7, 9-19, 2426, 28-31 of copending Application No. 18927411 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `411 are directed to method of using antibody-drug conjugate which has the structure shown in Formula Ab-(L-D)p comprising the anti-human Claudin 18.2 comprising 100% identical VH of claimed/referenced SEQ ID NO: 7/65 (41) and VL of claimed/referenced SEQ I DNO: 8/66(49) comprising the claimed CDRs, a linker and a cytotoxic agent.
The claims of the `411 applicant anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s arguments, filed 05/13/2026, have been fully considered, but have not been found convincing.
Applicants contend that the rejection of claims 1, 8, 12, and 18-30 on the ground of
nonstatutory double patenting as being unpatentable over the asserted claims of the '411
application should be withdrawn because the instant application has an earlier patent term filing
date than the '411 application. In support of this contention, Applicants note that M.P.E.P. §
804(1)(B)(1)(b)(i) states that:
If 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, thereby
converting the provisional nonstatutory double patenting rejection in the other
application into a nonstatutory double patenting rejection upon issuance of the
patent.
Applicants note that the instant application has a patent term filing date of October 19, 2021 (i.e.,
the filing date of International Application No. PCT/CN2021/124698) The '411 application has
a patent term filing date of October 25, 2024. Applicants therefore contend that the instant
application has an earlier patent term filing date than the '411 application.
However, the Provisional ODP rejection of record over co-pending application 18927411 is
maintained since the instant case is not yet allowable due to the new rejections above. Applicant
stated that the instant application should be issued since the filing date of this case is earlier than
that of 18927411. Applicant did not argue that the product in respective cases is different.
7. No claim is allowed.
8. 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 date of this final action.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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June 25, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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