DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/27/2026 has been entered.
Applicants Claim amendments/arguments in the response filed 5/27/2026 are acknowledged and entered into the record.
Accordingly, Claims 1, 2, 4, 5, 7, 9-17, 20, 22, 24-29, and 31-36 and newly added claims 37-42 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections Maintained - 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.
Claim(s) 1, 2, 4, 5, 7, 10-17, 20, 22, 24-29, 31-36 are rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al. (US Patent 10,093,736, referred to as Sahin A) in view of Sahin et al. (US Patent 10,813,996, referred to as Sahin B) and Liu (US Patent 11,912,763).
The claims are drawn to a method of treating cancer comprising administering to a patient an anti-CLDN18.2 antibody and an immune checkpoint inhibitor. The claims are further drawn to the anti-CLDN18.2 antibody having specific sequences (SEQ ID NOs: 17, 24, 32, 39) or previously deposited and wherein the checkpoint inhibitor is an anti-PD-1 antibody, anti-PD-L1 antibody, or anti-CTLA4 antibody and wherein the anti-CLDN18.2 antibody is not conjugated to interleukin-2.
Sahin A teach treatment of cancer comprising administering to a patient a binding agent targeting claudin and CD3. Sahin A discloses said claudin (CLDN) is CLDN18.2 and a binding agent comprising an antibody targeting CLDN18.2 an CD3. Sahin A discloses treatment of cancer represents a combination of strategies such that the methods and pharmaceutical compositions of the present invention may be effectively combined with various other drugs and/or methods (see column 60). Sahin A disclose additional antibodies which target PD-1 (nivolumab) and CTLA-4 (tremelimumab) can be used in combination with the anti-CLDN antibodies (see columns 62-63). Sahin A discloses anti-CLDN18.2 antibodies having CDRs and variable regions with 100% identity to SEQ ID NOs: 17, 24, and variable regions having 100% identity to SEQ ID NOs: 32 and 39, however does not disclose anti-CLDN18.2 antibodies produced or obtained from clones deposited under accession numbers recited in instant claim 15. This deficiency is made up for by Sahin B.
Sahin B teaches combination therapy for effectively treating diseases associated with cells expressing CLDN18.2 comprising administering to a patient an antibody binding to CLDN18.2. Sahin B discloses an anti-CLDN18.2 antibody which binds to the first extracellular loop of CLDN18.2 and antibodies produced by and/or obtainable from the same deposited clones as recited in instant claim 15 (see column 4).
Liu teach antibodies targeting CLDN18.2 and bispecific antibodies targeting an additionally non-CLDN18.2 antigen. Liu further discloses “methods of the present disclosure includes the administration of the anti-CLDN18.2 antibody molecule of the present disclosure to a subject in the amount effective for treatment or prevention of diseases (e.g., cancers), optionally, in combination with one or more inhibitors of PD-1, PD-L1, PD-L2, LAG-3, CTLA-4, Tim-3 antibody (immunotherapy) or other tumor therapeutic antibodies, Her-2, EGFR, VEGF, VEGFR antibody, etc., as well as ADC (antibody drug conjugate, such as T-DM1), bispecific antibody, chemotherapy drug, etc. Liu disclose the bispecific antibodies targeting CLDN18.2 and an immune checkpoint antigen including PD-1, PD-L1, showed synergistic effects (see table 38a).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the specific "CLDN18.2” antibodies taught by Sahin B in a method of treating cancer by administering a combination of anti-CLDN18.2 antibody and checkpoint inhibitor as taught by Sahin A. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the teachings of Sahin A & B and the specific anti-CLDN18.2, antibodies shown to successfully target tumors and slow tumor growth. It would have been obvious to extend the teachings of Sahin A to use the specific claudin18.2 antibodies taught by Sahin B in the method of combination therapy with a checkpoint inhibitor as taught by Sahin A for additional cancer treatment strategies. One of ordinary skill in the art would have been motivated to combine the anti-CLDN18.2 antibodies taught by Sahin A and Sahin B with immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA4 antibodies to enhance current cancer tumor treatment therapies. The instant situation is amenable to the type of analysis set forth in In re Kerkhoven (CCPA 1980) wherein the court held that if two modes of treatment, each of which is taught by the prior art to be useful for the same purpose in order to make a protocol that is to be used for the very same purpose since the idea of combining them flows logically from their having been individually taught in the prior art.
Response to Arguments
Applicant's argue in the response filed 5/27/2026 that Sahin A, Sahin B, nor Liu provide experimental evidence for the combination and its disclosure is purely speculative with respect to usefulness as a therapy and Liu et al. does not contemplate co-administration of an anti-CLDN18.2 antibody and immune checkpoint inhibitor as discrete agents and the recited combination therapy and the cited references amount to no more than a “hope” that the claimed combination would be useful to treat cancer. These arguments have been fully considered but they are not persuasive.
As stated before the references provide examples and experimental data showing the anti-CLDN18.2 antibodies inhibit tumor cell growth and/or kill tumor cells. Therefore, based on this data, one of ordinary skill in the art is not relying on just “hope” to have a reasonable expectation of success when combining the anti-CLDN18.2 antibodies with immune checkpoint inhibitors which are also well known in the art to inhibit tumor growth. Additionally, although the example provided by Liu et al. in table 38a uses a bispecific antibody to target both CLDN18.2 and PD-1, it is obvious to one of ordinary skill in the art to use other well known antibody formats when providing combination therapy and therefore administering the targeting agents discretely would be an obvious alternative based on the prior art and the teachings of all three references disclosing combinations of an antibody targeting claudin18.2 and an inhibitor of PD-1, PD-L1, or CTLA-4 as discrete agents. All the references are specific to the combining of anti-CLDN18.2 and checkpoint inhibitors and do not disclose long laundry lists of target antigens and therefore would render narrow reasonable expectation of success based on experimental data.
New Grounds of Rejection
(based on reconsideration)
Claims 1, 2, 4, 5, 7, 9-14, 16-17, 20, 22, 24-29, and 31-42 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (US Patent 11,447,551) as evidenced by the instant specification.
The claims are drawn to a method of treating cancer comprising administering to a patient an anti-CLDN18.2 antibody and an immune checkpoint inhibitor. The claims are further drawn to the anti-CLDN18.2 antibody having specific sequences (SEQ ID NOs: 17, 24, 32, 39) and wherein the checkpoint inhibitor is an anti-PD-1 antibody, anti-PD-L1 antibody, or anti-CTLA4 antibody and wherein the anti-CLDN18.2 antibody is not conjugated to interleukin-2.
Zhu et al. teach “compositions and methods of making isolated binding molecules (e.g. an antibodies) or antigen-binding fragment thereof useful as therapeutics for treating and/or preventing diseases associated with cells expressing claudin18.2” (see Abstract). Zhu et al. further teaches “pharmaceutical formulations comprising the described compositions for the treatment of diseases either as single agent (e.g., naked antibodies) or as adjuvant therapy with other antigen-binding anticancer agents such as immune checkpoint inhibitors (e.g., anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies), and/or by combination therapies where the anti-claudin18.2 antibodies are administered before, after, or concurrently with chemotherapy” (see Abstract). Zhu et al. discloses the anti-CLDN18.2 antibody “IMAB362 (Claudiximab, Zolbetuximab)”, which the instant specification discloses comprises a VH having instant SEQ ID NO: 51 and VL having instant SEQ ID NO: 24 (see instant specification p.2). Zhu et al. further discloses anti-PD-1 antibodies pembrolizumab and nivolumab and anti-CTLA4 antibody ipilimumab. Zhu et al. discloses IMAB362 can be administering at single doses up to 1000 mg/m2. Zhu et al. disclose the combined therapies comprise administration of an anti-CLDN18.2 binding molecule in combination with administration of another therapeutic agent (e.g., an anti-PD-1, anti-PD-L1, or anti-CTLA4 antibody), the methods disclosed herein encompass co-administration, using separate formulations or a single pharmaceutical formulation, and consecutive administration in either order. Zhu et al. discloses of combination methods described in paragraphs (280) to (296).
Although Zhu et al. does not explicitly teach an example of combining an anti-claudin18.2 antibody and a checkpoint inhibitor, the reference clearly recites obvious motivation to practice the combination based on the findings that anti-claudin18.2 antibody, zolbetuximab (IMAB362), showed survival benefit and tumor regression after administration (see paragraph (9)). Additional anti-claudin18.2 antibodies disclosed in Zhu et al. also were shown to inhibit tumor growth and increase survival benefit (see Fig. 47). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to reduce to practice the explicit methods of combining anti-caludin18.2 antibodies with checkpoint inhibitors such as anti-CTLA and anti-PD-1 antibodies taught by Zhu et al. One of ordinary skill in the art would have had a reasonable expectation of success based on the teachings of Zhu et al. that anti-claudin18.2 antibodies are capable of inhibiting tumor growth and previous combination studies have shown increased benefit.
All other previous rejections are hereby withdrawn in view of applicants claim amendments in the response filed 5/27/2026.
Conclusion
Claims 1, 2, 4, 5, 7, 9-17, 20, 22, 24-29, 31-42 are rejected.
No Claim is allowed.
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/Meera Natarajan/Primary Examiner, Art Unit 1643
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