DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s reply filed on 2/13/2026 is acknowledged. New claims 108-109 have been added. Claims 82, 84-93 and 96-109 are pending. Claims 1-81, 83 and 94-95 are canceled. No claims have been amended.
3. Claims 82, 84-93 and 96-109 are under examination.
Rejections Withdrawn
4. The rejection of claim 94 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of applicant’s cancellation of the claim.
Rejections Maintained
Double Patenting
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).
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6. Claims 82, 84-89, 93 and 96-101 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,795,218, in view of Sahin et al. (WO2011057788A1, pub. date: 5/19/2011, IDS dated 6/22/2023), and Horiguchi et al (Anticancer Research, 2009, 29:517-524).
Claims 1-22 of U.S. Patent No. 11,795,218 disclose a method for treating a cancer patient having a cancer characterized by cancer cells expressing CLDN6 on the cell surface, said method comprising: administering to the patient (i) an anti-CLDN6 antibody and (ii) an agent of chemotherapy, wherein the antibody comprises (a) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 5 or a variant thereof wherein said variant comprises complementarity determining regions CDR1, CDR2, and CDR3 that are identical to complementarity determining regions of SEQ ID NO: 5 and said variant of SEQ ID NO: 5 has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 5 and (b) a light chain variable region (VL) comprising (b1) the amino acid sequence of SEQ ID NO: 4 or a variant thereof wherein said variant comprises complementarity determining regions CDR1, CDR2, and CDR3 that are identical to complementarity determining regions of SEQ ID NO: 4 and said variant of SEQ ID NO: 4 has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 4 or (b2) the amino acid sequence of SEQ ID NO: 12 or a variant thereof wherein said variant comprises complementarity determining regions CDR1, CDR2, and CDR3 that are identical to complementarity determining regions of SEQ ID NO: 12 and said variant of SEQ ID NO: 12 has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 12, and wherein the agent of chemotherapy comprises a multi-chemotherapy comprising cisplatin, etoposide and bleomycin (PEB),
wherein the cancer involves cancer stem cells expressing CLDN6, the cancer stem cells are at a tumor site of the cancer patient, administering the antibody results in inhibition or elimination of cancer stem cells expressing CLDN6,
wherein administering the antibody having the ability of binding to CLDN6 enhances the anti-cancer effect of chemotherapy,
wherein the cancer is resistant to chemotherapy, the cancer is resistant to chemotherapy administered as monotherapy.
wherein the antibody exerts its inhibitory and/or cytotoxic effect on the cancer cells by mediating one or more of complement dependent cytotoxicity (CDC) mediated lysis, antibody dependent cellular cytotoxicity (ADCC) mediated lysis, induction of apoptosis and inhibition of proliferation,
where the antibody is coupled to a therapeutic moiety, the therapeutic moiety is a cytotoxic agent, a chemotherapeutic agent or a radionuclide.
wherein the cancer comprises primary cancer, advanced cancer, metastatic cancer, recurrent cancer or a combination thereof.
The amino acid sequences of SEQ ID NOs: 4, 5 and 12 are 100% identical to instant SEQ ID NOs: 4, 5 and 12, respectively.
The claims of the patent do not disclose treating paclitaxel resistant cancer.
Sahin et al. teaches a method of treating cancer expressing CLDN6 including breast cancer comprising administering an anti-CLDN6 antibody to a cancer patient (pages 18-19 and claims), and a chemotherapeutic agent such as doxorubicin (anthracyclines), cisplatin (pages 20, 66, 85 and 94-95).
Horiguchi et al teaches that patients with HER2-negative breast cancer are typically resistant to chemotherapy, and paclitaxel monotherapy is often insufficient to allow patients with advanced breast cancer to achieve pCR (page 520, column 2).
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 have treated paclitaxel resistant cancer with the method of the patent in view of Sahin and Horiguchi. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because the claims of the patent disclose a method of treating chemo resistant cancer, and Sahin et al teaches treating breast cancer with an anti-CLDN6 antibody and chemotherapy, and Horiguchi et al teaches that patients with HER2-negative breast cancer are typically resistant to chemotherapy.
7. Claims 82, 84-93, 96-107 and new claims 108-109 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,795,218, in view of Sahin et al. (WO2011057788A1, pub. date: 5/19/2011, IDS dated 6/22/2023), and Horiguchi et al (Anticancer Research, 2009, 29:517-524), further in view of Heartlein et al. (US 10,087,247B2, date of patent: 10/2/2018, filing date: 3/14/214, effectively filed date: 3/14/2013).
The teachings of the claims of the patent, Sahin and Horiguchi have been set forth above as they apply to claims 82, 84-89, 93 and 96-101.
The claims of the patent, Sahin and Horiguchi do not teach administering one or more nucleic acids encoding the anti-CLDN6 antibody to treat cancer.
Heartlein et al. teaches a method of delivering an antibody in vivo, the method comprising: administering systemically to a subject in need thereof a first mRNA polynucleotide encoding a heavy chain and a second mRNA polynucleotide encoding a light chain of the antibody, wherein the first mRNA and the second mRNA are encapsulated in liposomes, and wherein the antibody is detectable in the serum of the subject for more than 72 hours post-administration (claim 1).
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 have modified the method of the patent to deliver the antiCLDN6 antibody by polynucleotides in view of Heartlein et al. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Heartlein et al. teaches delivering antibody by polynucleotides and has shown that such delivered antibody is detectable in the serum of the subject for more than 72 hours post-administration.
Applicant’s Response
The response states that Applicants disagree that the Office has established a prima facie case of obviousness. Applicants note that Horiguchi does not teach or suggest treatment of a cancer that is resistant to chemotherapy and characterized by cancer cells expressing CLDN6 on the cell surface by the combinatorial approach claimed herein. Horiguchi merely acknowledged that "paclitaxel monotherapy is often insufficient to allow patients with advanced breast cancer to achieve pCR." Horiguchi, page 520, col. 2.
Nevertheless, and without conceding to the propriety of the rejection, Applicants note that the present specification demonstrates an unexpected result. The specification states:
It is also demonstrated that therapy using CLDN6 specific antibodies can overcome the chemotherapeutic resistance of tumors such as ovarian cancer and the combination of chemotherapy and CLDN6 antibody therapy has a remarkable synergistic effect. Specification, page 3.
Indeed, it was the present application that first provided evidence that the recited combination therapy increases inhibition of tumor growth and prolongs survival in a mouse model. See, e.g., Example 8.2 and Figure 16B. In particular, the present specification explains that "[a] sustainable inhibition of tumor growth was only achieved in a combined approach in which PEB and IMAB027 act synergistically together." Id. at page 100 (emphasis added). In fact, the specification notes that while only 21% (3/14) of mice treated with PEB alone achieved complete tumor regression, "surprisingly, complete tumor regression was observed in 12/14 (86%) mice treated with PEB in combination with IMAB027." Id. This surprising, synergistic effect is an unexpected benefit and constitutes objective evidence that the recited combination in the claimed method would not have been obvious to a person of ordinary skill in the art.
The Office has not provided any basis to question Applicants' statements in the specification. In the absence of evidence to the contrary, Applicants' presentation of data demonstrating synergy and statement that the results were surprising "should suffice to establish unexpected results." In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995). The Office has presented no such evidence.
Examiner’s Response
Applicant’s arguments have been carefully considered but are not persuasive.
Claims 1-22 of U.S. Patent No. 11,795,218 disclose a method for treating a cancer patient having a cancer characterized by cancer cells expressing CLDN6 on the cell surface, said method comprising: administering to the patient (i) an anti-CLDN6 antibody and (ii) an agent of chemotherapy, wherein the antibody is identical to the instant antibody and the agent of chemotherapy comprises a multi-chemotherapy comprising cisplatin, etoposide and bleomycin (PEB), wherein the cancer involves cancer stem cells expressing CLDN6, the cancer stem cells are at a tumor site of the cancer patient, administering the antibody results in inhibition or elimination of cancer stem cells expressing CLDN6, wherein administering the antibody having the ability of binding to CLDN6 enhances the anti-cancer effect of chemotherapy, wherein the cancer is resistant to chemotherapy, the cancer is resistant to chemotherapy administered as monotherapy, where the antibody is coupled to a therapeutic moiety, the therapeutic moiety is a cytotoxic agent, a chemotherapeutic agent or a radionuclide.
As one can see, the claims of the patent disclose every limitation of instant claims 82, 84-86, 88-89, 93, 96-98 and 100-101 and thus anticipate these claims. Accordingly applicant’s arguments of unexpected results are not applicable to the rejection of these claims (anticipation based rejection).
Regarding claims 87 and 99, although the claims of the patent disclose treating cancer which is resistant to chemotherapy, in particular cancer which is resistant to chemotherapy administered as monotherapy, they do not disclose treating cancer which is resistant to paclitaxel monotherapy.
Sahin et al. teaches a method of treating cancer expressing CLDN6 including breast cancer comprising administering an anti-CLDN6 antibody to a cancer patient (pages 18-19 and claims), and a chemotherapeutic agent such as doxorubicin (anthracyclines), cisplatin (pages 20, 66, 85 and 94-95).
Horiguchi et al teaches that patients with HER2-negative breast cancer are typically resistant to chemotherapy, and paclitaxel monotherapy is often insufficient to allow patients with advanced breast cancer to achieve pCR (page 520, column 2).
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 have treated paclitaxel resistant cancer with the method of the patent in view of Sahin and Horiguchi. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because the claims of the patent disclose a method of treating chemoresistant cancer, and Sahin et al teaches treating breast cancer with an anti-CLDN6 antibody and chemotherapy, and Horiguchi et al teaches that patients with HER2-negative breast cancer are typically resistant to chemotherapy.
Applicant’s arguments of unexpected results are not persuasive because the claims of the patent teaches treating chemoresistant cancer with same anti-CLDN6 antibody and same chemotherapy (PEB). Regarding claims 87 and 99, applicant has not shown unexpected results that are specific to treating paclitaxel resistant cancer.
For the foregoing reasons, the rejection is deemed proper and is therefore maintained.
Conclusion
8. No claims are allowed.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
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/HONG SANG/Primary Examiner, Art Unit 1646