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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/22/2025 has been entered.
The rejection under section 103 is maintained.:
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 69-96 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2008145338 (WO 338) in view of Jain et al., Pharm Res (2015) 32:3526–3540, Epub 2015 Mar 11(Jain) and Chari et al., Angew. Chem. Int. Ed. 2014, 53, 3796 – 3827 (Chari).
WO 338 teaches the recited abti-CLDN18.2 antibody. See attached GenCore version 6.4.1, Copyright (c) 1993 - 2021 Biocceleration Ltd., Anti-claudin-18, ATY94639 (heavy chain) SEQ ID NO:118 and ATY94646 (light chain) SEQ ID NO: 152, corresponding to the recited SEQ ID NO’s: 17 and 24, respectively:
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WO 338 also teaches conjugates of these antibodies for the treatment of the recited cancers:
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See page 9.
The difference between WO 338 and the instant conjugates is that WO 338 may fail to explicitly teach that the antibody is covalently attached to the at least one toxin drug moiety via a linker that is cleavable under intracellular conditions. However, the secondary references demonstrate that these linker-toxins are ubiquitous in the art.
See Jain, teaching VAL-Cit-MMAE which is cleaved intracellularly:
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SPDP-DM1 and -DM4 payloads:
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In this way, those of ordinary skill could have applied the linker-toxins of Jain in the manner required and in a predictable fashion for the purposes of obtaining the recited conjugates for cancer treatment. As outlined above, WO 338 teaches anti-CLDN antibody conjugates for cancer treatment. Jain is added for the proposition that the recited linker-toxins are applicable to these conjugates. Specifically, Jain teaches the particular known technique of using the recited linker-toxins for cancer treatment was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to antibody conjugates, such as those taught by WO 338, would have yielded predictable results. Accordingly, using the recited linker-toxins for the purposes of preparing anti-CLDN antibody conjugates for cancer treatment would have been prima facie obvious.
Applicant argues that the Office has not adequately identified any reason to select ch-182- D1106-362 over any other antibody disclosed by the WO'338 Publication for conjugation to at least one toxin drug moiety via a linker that is cleavable under intracellular conditions to make a therapeutically useful ADC (i.e., an ADC that could be used in a method of treating a cancer). Nor has the Office adequately identified any reason that would have provided a POSA with a reasonable expectation of success.
However, WO 338 expressly identifies ch-182- D1106-362 (a.k.a, anti-claudin 18.2 antibody 166E2, “166E2”) as a clinical lead candidate because of its ability to bind to human CLD18A2 but not to human CLD18A1, bind to CLD18 naturally expressed by tumor cells, mediate CDC induced killing of cells, which express CLD18. Specifically, WO 338 identifies the antibody as one that can bind to CLD18 in intercellular contact zones, see page 122:
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These are the same criteria for leads in antibody-drug conjugates, for example, high target specificity: binds exclusively or predominantly to antigens on tumor cells, avoiding normal tissues; high affinity: strong binding to the target antigen for efficient delivery and internalization: promotes rapid internalization into the cancer cell after binding; see Chari, page 3803.
In this manner, WO 338 describes a finite number of anti-claudin 18.2 antibody candidates for antibody- drug conjugates (ADC), including 166E2. Chari demonstrates that development 166E2 is preferred since the antibody demonstrates critical criteria for an antibody in an ADC. Specifically, it would have been obvious for one having ordinary skill in the art to make ADC’s with those antibodies exemplified by WO 338, including 166E2, and with a reasonable expectation that the resulting ADC’s would be useful in treating cancer, since the antibodies are prime candidates for ADC development. In this connection, the references demonstrate that the exemplified ADC’s possess the required characteristics, outlined above; and it would have been obvious to one of ordinary skill to choose from this finite number of antibody options with a reasonable expectation of success of producing a functional ADC.
With regard to any unpredictability associated with the antibodies, the notion that unpredictability confers patentability in this case of known anti-claudin 18.2 antibodies should be disregarded since a rule of law equating unpredictability to patentability, applied in this case, would mean that any new ADC based on a different antibody disclosed by WO 338 would be separately patentable, simply because the formation and properties of each ADC must be verified through testing. This cannot be the proper standard since the expectation of success need only be reasonable, not absolute.
Here, the references provide the reasonable expectation of success, as outlined above. Namely, the references demonstrate the reasonable expectation of success since the references sufficiently characterize the instant antibody and its characteristics Again, the expectation of success need only be reasonable, as it is here, and not absolute, (“obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).”).
With regard to any alleged unexpected property possessed by those ADC’s with the 166E2 antibody, it is error to assume that any superior property is unexpected, especially in the instant case, where the pharmacodynamic and pharmacokinetic properties of different ADC’s are not predictable. In this case, one skilled in the art would expect different antibodies to provide ADC’s having a range of properties, some of which would be superior, and some of which would be inferior.
Rather, Applicant has conducted a common optimization of the known anti-claudin 18.2 antibodies described by WO 338 to produce the claimed ADC, which is routine. Specifically, Applicant engaged in routine, verification testing to optimize selection of one of several known and clearly suggested antibodies to prepare a pharmaceutically-acceptable conjugate.
Again, any alleged unexpected results are not probative across the entirety of the genus of conjugates. Applicant has not demonstrated any unexpected results, especially with regard to the Val-Cit MMAE or SPDB-DM4 conjugates, which Jain demonstrates as ubiquitous in the art.
The obvious double patenting rejections are maintained, specifically, for at least the reasons stated above in the rejection under section 103 for the combination of the conflicting claims and the secondary references.
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 69-96 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claim 29 of U.S. Patent No. 11732308 in view of WO 2008145338 (WO 338) and Jain et al., Pharm Res (2015) 32:3526–3540, Epub 2015 Mar 11(Jain) and Chari.
Although the claims at issue are not identical, they are not patentably distinct from each other. Specifically, the conflicting claims cover methods of treating cancer with anti-CLDN antibody conjugates that anticipate the rejected claims. Alternatively, the difference between the conflicting claims and the rejected claims is that the conflicting claims may not recite the instant conjugates with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the instant conjugates invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the conjugates would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143). In this regard, the secondary references demonstrate that the instant anti-CLDN antibody conjugates were within the purview of those of ordinary skill, and therefore, prima facie obvious.
Claims 69-96 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claim 19 of U.S. Patent No. 11541127 in view of WO 2008145338 (WO 338) and Jain et al., Pharm Res (2015) 32:3526–3540, Epub 2015 Mar 11(Jain) and Chari.
Although the claims at issue are not identical, they are not patentably distinct from each other. Specifically, the conflicting claims cover methods of treating cancer with anti-CLDN antibody conjugates that anticipate the rejected claims. Alternatively, the difference between the conflicting claims and the rejected claims is that the conflicting claims may not recite the instant conjugates with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the instant conjugates invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the conjugates would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143). In this regard, the secondary references demonstrate that the instant anti-CLDN antibody conjugates were within the purview of those of ordinary skill, and therefore, prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Janet Epps-Smith, can be reached at telephone number (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646