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 .
Claims 1-58 have been cancelled.
Election/Restrictions
Applicant’s election without traverse of Group I, and the species outlined on page 11 of the 4/9/2026 response, in the reply filed on 4/9/2026 is acknowledged. The elected species has the general structure of instant Figure 1B.
Claims 66, 72, and 77-80 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 4/9/2026.
Specification
The substitute specification filed 4/9/2026 has been entered.
Drawings
The replacement drawings (sheets 1/27) submitted 11/18/2024 are acceptable.
Claim Rejections - 35 USC § 102
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.
(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 59-63, 65, 70, and 76 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (U.S. Patent Application Publication 2018/0110875, of record).
Liu et al. (U.S. Patent Application Publication 2018/0110875) is an English language equivalent of CN 111196853 (cited on search report). U.S. Patent No. 10,543,284 and WO 2016/165580 are also equivalent documents.
Liu et al. discloses an antibody drug conjugate (ADC) (i.e. a targeting conjugate) having an anti-c-Met antibody (targeting moiety) conjugated to a cytotoxic agent such as a chemotherapeutic agent (effector molecule) by a cleavable linker. See at least claims 26 and 28-29 and paragraphs [0006 and 0164]. For example, these constructs meet the limitations of instant claim 59 and the formula of instant claim 60 where a, b, and x are all one and where u, v, y, and z are all zero. With respect to instant claims 61-63, cleavage can occur at an in vivo target site by proteolytic cleavage. See at least paragraphs [0163-0164]. With respect to instant claim 65, a chemotherapeutic agent is a therapeutic agent. With respect to claim 70, c-Met is a tumor antigen. With respect to instant claim 76, a pharmaceutical composition of the ADC would have a plurality of targeting conjugates. Pharmaceutical compositions are disclosed in at least the abstract.
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.
Claims 59-65, 70, and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (U.S. Patent Application Publication 2018/0110875, of record) as applied to claims 59-63, 65, 70, and 76 above, and further in view of Boyd et al. (U.S. Patent Application Publication 2008/0279868) and Madison et al. (WO 97/47314).
Liu et al. is applied as above but does not disclose the protease urokinase (i.e. uPA) and the cleavage sites recited in claim 64.
Boyd et al. (U.S. Patent Application Publication 2008/0279868) discloses that the presence of urokinase at a cancer site was correlated with an increased ability to metastasize. The reference discloses that antibody drug conjugates (ADC) can use linker peptide sequences that are cleaved by urokinase. See at least paragraph [0327].
Madison et al. (WO 97/47314) discloses SEQ ID NO: 12 which is identical to instant SEQ ID NO: 53. This peptide is a substrate for selective cleavage by u-PA. See at least Table 1 on page 21. Instant SEQ ID NO: 53 includes the sequences of instant SEQ ID NOS: 54 and 55.
It would have been obvious to use the peptide of SEQ ID NO: 12 of Madison et al. as the protease cleavage site in the ADC of Liu et al. One would have been motivated to do so as Boyd et al. makes clear that urokinase would be present at a target site of disease and ADC with linker peptide sequences that are cleaved by urokinase would be useful.
Claims 59-63, 65, 68-70, and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (U.S. Patent Application Publication 2018/0110875, of record) as applied to claims 59-63, 65, 70, and 76 above, and further in view of Pons et al. (U.S. Patent Application Publication 2013/0230543).
Liu et al. is applied as above but does not disclose the transglutaminase conjugation site of claim 68-69.
Pons et al. discloses antibody drug conjugates (ADC) where the drug is conjugated to the antibody using an acyl donor glutamine-containing tag and an amino donor agent. See at least abstract and claims. The glutamine tag can be at the end of the heavy chain and can contain sequences such as LLQGG (SEQ ID NO: 2) (see C in instant claim 60). See at least claims 4 and 7. Note that instant SEQ ID NO: 13 corresponds to LLQGG. (See instant claim 69.) The amine donor unit-linker (X-Y) can be, for example, amino-PEG3-C2 or amino-PEG6-C2 (see L in instant claim 60 and instant specification paragraphs [0124, 0127, and 0173-0174]. The cytotoxic agent can be, for example, SN-38 (see D in instant claim 60). See at least claims 13-18. The antibody can be bispecific. See at least paragraph [0081] and claims 10.
It would have been obvious to use the transglutaminase conjugation technique to conjugate a chemotherapeutic agent such as SN-38 (as taught by Pons et al.) to the antibody construct of Liu et al. One would have been motivated to do so as Pons et al. makes clear that this would have been a well-known method of conjugation at the time of the effective filing date. This embodiment would have v = 1 in instant claim 60.
Claims 59-65, 68-71, and 73-76 are rejected under 35 U.S.C. 103 as being unpatentable over Pons et al. (U.S. Patent Application Publication 2013/0230543).in view of Zhao et al. (2019, of record), Goldenberg et al. (U.S. Patent Application Publication 2016/0313339), Brinkmann et al. (2017), Govindan et al. (U.S. Patent Application Publication 2017/0313781), Boyd et al. (U.S. Patent Application Publication 2008/0279868), and Madison et al. (WO 97/47314).
Pons et al., Boyd et al., and Madison et al. are applied as above.
Brinkmann et al. discloses bispecific antibodies where an scFv is fused at the C- terminus of an antibody heavy chain. This IgG-Hc-scFv format is shown in Figure 2, Box 10, 1st construct on left. Bispecific antibodies in this format would have been well known.
Zhao et al. discloses that bispecific anti-Trop2/anti-PD-L1 antibodies are useful in treating gastric cancer. Both antibodies are scFv. See at least abstract and materials and methods on page 1847
Goldenberg et al. (U.S. Patent Application Publication 2016/0313339) discloses bispecific anti-Trop-2 antibodies where the second specificity can be an anti-PD-L1 antibody. See at least paragraph [0015].
Govindan et al. discloses ADC where SN-38 can be conjugated to an anti-Trop-2 antibody.
Pons et al. discloses conjugating drugs to antibodies at the end of the heavy chain using a transglutaminase conjugation site where the antibody can be bispecific. Brinkmann et al. discloses the well known bispecific format IgG-Hc-scFv. Zhao et al. and Goldenberg et al. disclose that bispecific anti-Trop2/anti-PD-L1 would have been useful. Targeting immune checkpoint molecules (i.e. PD-L1) and tumor antigens (Trop-2) would have been known. Govindan et al. discloses that conjugating the drug SN-38 to an anti-Trop-2 antibody would have been useful. It would have been obvious to produce a bispecific IgG-Hc-scFv antibody according to Brinkmann et al. where the IgG-Hc portion was an anti-PD-L1 antibody and the scFv portion was an anti-Trop-2 scFv. It would have been obvious to include a transglutaminase conjugation site at the end of the anti-PD-L1 antibody heavy chain as suggested by Pons et al. in order to conjugate a drug such SN-38 as suggested by Govindan et al. One would have been motivated to do so in order to produce useful therapeutic compounds. It would have been obvious to optionally include a cleavable linker between the anti-PD-L1 antibody portion and the conjugated anti Trop-2 scFv portion using the peptide of SEQ ID NO: 12 of Madison et al. which is a substrate for urokinase. One would have been motivated to do so as Boyd et al. makes clear that urokinase would be present at a target site of disease and ADC with linker peptide sequences that are cleaved by urokinase would be useful.
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 59-65, 67-71, and 73-76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 10, 12, 14, 17-23, 26-32, 39, and 47-49 of copending Application No. 19/486,863 (11/21/2025 claim set). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to antibody drug conjugates having the same characteristics and pharmaceutical compositions thereof.
Copending claim 1 is directed to embodiments of instant claims 59-60. Co-pending claim 6 and 10 disclose the limitations of instant claims 61-64. Co-pending claim 17 discloses the limitations of instant claims 68-69. Co-pending claim 18 discloses the limitations of instant claim 67. The co-pending claims recite a first targeting moiety specifically recognizing PD-L1 (first immune checkpoint molecule) and a second targeting moiety specifically recognizing Trop-2 (a tumor antigen). See instant claims 70-71 and 73-75. Co-pending claim discloses the limitations of instant claim 76.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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