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 .
Applicant’s amendments, filed 12/04/2025, is acknowledged.
Claim 9 is cancelled.
Claims 1-8 and 10-21 are currently pending and are under examination.
In view of the amendments and remarks filed on 12/04/2025, the following rejections remain.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-8 and 13-17 stand rejected under 35 U.S.C. 103 as being unpatentable over Dimitrov et al. (U.S. PGPub 20180186890, in Office Action mailed 7/11/2025) in view of Schlothauer et al. (Protein Eng Des Sel. 2016 Oct;29(10):457-466. doi: 10.1093/protein/gzw040. Epub 2016 Aug 29, in Office Action mailed 7/11/2025) and Thompson et al. (J Control Release. 2016 Aug 28;236:100-16. doi: 10.1016/j.jconrel.2016.06.025. Epub 2016 Jun 18, in Office Action mailed 7/11/2025), as evidenced by UnitProt entry P01857 (sequence version 01/18/2017; https://rest.uniprot.org/unisave/P01857?format=fasta&versions=183, in Office Action mailed 7/11/2025), Bao et al. (Breast Cancer Res. 2015 Oct 14;17(1):137. doi: 10.1186/s13058-015-0615-y), and Hardwick et al. (Cancer Genet Cytogenet. 2002 Nov;139(1):48-51. doi: 10.1016/s0165-4608(02)00604-0).
Claims 1-8 and 13-17 stand rejected for the same reasons discussed in the Office Action mailed on 7/11/2025.
Applicant’s arguments and amendments, filed 12/04/2025, have been fully considered, but have been found to be not convincing.
Instant claim 1 has been amended to limit the ADC drug conjugate to a PBD dimer, and this limitation was included in the 35 U.S.C § 103 rejection in the Office Action mailed 7/11/2025.
Applicant argues that the instantly claimed ADC, m276 with the S239C, L234A, L235A, and P329G Fc point mutations, conjugated to a PBD dimer at position 239, has unexpectedly superior results to the m276-PBD dimer taught by Dimitrov et al., which is the m276-PBD ADC without the indicated Fc mutations. Applicant argues (pg. 7 of Remarks):
“Additional studies were performed to directly compare the claimed m276-PBD-SL ADC to the m8524-PBD ADC disclosed in Dimitrov et al. ("m8524-PBD" is referred to as "m276-PBD" in Applicant's specification and this term is used below). In a first study, m276-PBD was tested in an orthotopic Py230 breast cancer model. Mice bearing Py230 tumors were administered vehicle or 1 mg/kg m276-PBD twice per week for four weeks. Treatment was initiated when the average tumor volume reached 140 mm3. As shown in Applicant's FIG. 5, breast tumors in all mice treated with m276-PBD glycoconjugate initially regressed and then relapsed after treatment. As a comparison, the m276-PBD-SL ADC was evaluated in a large orthotopic MDA-MB-231 breast cancer model. Treatment was initiated when the average tumor volume reached 1000 mm3. Mice bearing MDA-MB-231 tumors were administered vehicle, 0.1 mg/kg m276-PBD-SL or 0.5 mg/kg m276-PBD-SL once per week for five weeks. As shown in Applicant's FIG. 6, relapse occurred in some of the mice treated with the lower (0.1 mg/kg) dose, but complete responses were observed in all mice treated with the higher (0.5 mg/kg) dose of m276-PBD-SL. Thus, a lower dose (0.5 mg/kg) of m276-PBD-SL was able to successfully treat larger tumors (1000 mm3) than a higher dose (1 mg/kg) of the m276-PBD glycoconjugate was able to treat smaller tumors (140 mm3).”
This has been found to be not convincing. The m276-PBD antibody (i.e., the antibody taught by the prior art) was tested for inhibiting tumor growth of the Py230 cell line in mice, and the m276-PBD-SL (i.e., the antibody encompassed by the instant claims) was tested for inhibiting tumor growth of MDA-MB-231 cells in mice.
Bao et al. is used as an evidentiary reference to demonstrate that Py230 cells are mouse cells (pg. 2, Introduction): “…clonal cell lines were derived from the transgenic polyomavirus middle T (PyVmT) oncogene mouse model of luminal tumorigenesis in both the C57Bl/6 and FVB/N strains…[w]e have focused this report on the C57Bl/6 Py230 cell line…”
Bao et al. further teaches that the Py230 cells injected into mice differentiate into different types of mouse breast cancer carcinomas (Results): “[w]hen implanted into the mammary fat pads of syngeneic immune competent C57Bl/6 mice, Py230 cells form mammary intraepithelial neoplasia (MIN), from which a subset of cells develop into well-differentiated carcinomas and then poorly differentiated carcinomas that metastasize to the lungs… Py230 cells that are ER- and PR-negative under normal in vitro culture conditions, can upregulate ERα expression in estrogen-depleted media, and can form ER- and PR- positive tumors in vivo…”.
Hardwick et al. is used as an evidentiary reference to demonstrate the MDA-MB-231 cells are aggressive ER negative human breast cancer cells (Discussion): “…MDA-MB-231 cells, which are an aggressive, estrogen receptor (ER) negative human breast cancer cell line…”
The mouse Py230 cell line is a mouse cell line that differentiates into different types of carcinomas when injected into mice, and the MDA-MB-231 cell line is a differentiated triple-negative human cancer cell line. These two cell lines have different lineages (mouse vs human), proliferation rates, and surface expression of different receptors including ER, and therefore one with ordinary skill in the art would not expect tumors comprising these different cell lines to have the same response to therapies.
While the efficacy of the m276-PDB in treating Py230 tumors was tested and measured (instant Figure 5), no comparable test of m276-PDB-SL in treating mice harboring these tumors is not disclosed to allow for a comparison of these two antibodies in treating Py230 mouse tumors. Additionally, while the efficacy of the m276-PDB-SL in treating MDA-MB-231 tumors (instant Figure 6), no comparable test of m276-PDB in treating mice harboring these tumors is not disclosed to allow for a comparison of these two antibodies in treating MDA-MB-231. Therefore, there is currently insufficient evidence to demonstrate unexpectedly superior results.
A comparison of the antibody taught by the prior art (m276-PDB) and the antibody encompassed by the instant application (m276-PDB-SL) in treating tumors from the same cell line would be able to demonstrate the m276-PDB-SL had unexpected superior results over the prior art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Dimitrov et al. in view of Schlothauer et al. (supra) and Thompson et al. (supra), as evidenced by UnitProt entry P01857 (supra), Bao et al. (supra), and Hardwick et al. (supra), as applied to claims 1-8 and 13-17 above, and further in view of Tiberghien et al. (ACS Med Chem Lett. 2016 May 24;7(11):983-987. doi:10.1021/acsmedchemlett.6b00062, in Office Action mailed 7/11/2025).
The invention as a whole was prima facie obvious to one of ordinary skill in the art for the reasons discussed in the Office Action mailed 7/11/2025.
Applicant’s arguments and amendments, filed 12/04/2025, have been fully considered, but have been found to be not convincing.
Applicant has argued that the instantly claimed invention has unexpected superior results over the prior art, however that has been found to be not convincing for the reasons discussed supra.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 16 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Dimitrov et al. in view of Schlothauer et al. (supra) and Thompson et al. (supra), as evidenced by UnitProt entry P01857 (supra), Bao et al. (supra), and Hardwick et al. (supra), as applied to claims 1-8 and 13-17 above, and further in view of Vogus et al. (J Control Release. 2017 Dec 10;267:191-202. doi: 10.1016/j.jconrel.2017.08.016. Epub 2017 Aug 18, in Office Action mailed on 7/11/2025).
The invention as a whole was prima facie obvious to one of ordinary skill in the art for the reasons discussed in the Office Action mailed 7/11/2025.
Applicant’s arguments and amendments, filed 12/04/2025, have been fully considered, but have been found to be not convincing.
Applicant has argued that the instantly claimed invention has unexpected superior results over the prior art, however that has been found to be not convincing for the reasons discussed supra.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-8 and 13-17 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 10,604,582 (herein Pat '582, in Office Action mailed 7/11/2025) in view of Dimitrov et al. (U.S. PGPub 20180186890, in Office Action mailed 7/11/2025, supra), Schlothauer et al. (Protein Eng Des Sel. 2016 Oct;29(10):457-466. doi: 10.1093/protein/gzw040. Epub 2016 Aug 29, in Office Action mailed 7/11/2025, supra) and Thompson et al. (J Control Release. 2016 Aug 28;236:100-16. doi: 10.1016/j.jconrel.2016.06.025. Epub 2016 Jun 18, in Office Action mailed 7/11/2025, supra), as evidenced by UnitProt entry P01857 (sequence version 01/18/2017, in Office Action mailed 7/11/2025, supra), Bao et al. (Breast Cancer Res. 2015 Oct 14;17(1):137. doi: 10.1186/s13058-015-0615-y, supra), and Hardwick et al. (Cancer Genet Cytogenet. 2002 Nov;139(1):48-51. doi: 10.1016/s0165-4608(02)00604-0, supra).
The invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by Pat ‘582 in view of Dimitrov et al., Schlothauer et al., and Thompson et al., as evidenced by UnitProt entry P01857, Bao et al., and Hardwick et al. for the same reasons discussed in the Office Action mailed 7/11/2025.
Applicant’s arguments and amendments, filed 12/04/2025, have been fully considered, but have been found to be not convincing.
Applicant has argued that the instantly claimed invention has unexpected superior results over the prior art, however that has been found to be not convincing for the reasons discussed in the 35 U.S.C.§ 103 rejection supra.
Therefore, the invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by Pat ‘582 in view of Dimitrov et al., Schlothauer et al., and Thompson et al., as evidenced by UnitProt entry P01857, Bao et al., and Hardwick et al.
Claims 10-12 stand as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 10,604,582 (Pat '582, supra) in view of Dimitrov et al. (supra), Schlothauer et al. (supra) and Thompson et al. (supra), as evidenced by UnitProt entry P01857 (supra), Bao et al. (supra), and Hardwick et al. (supra), as applied to claims 1-8 and 13-17 above, and further in view of Tiberghien et al. (ACS Med Chem Lett. 2016 May 24;7(11):983-987. doi:10.1021/acsmedchemlett.6b00062, in Office Action mailed 7/11/2025, supra).
The invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by Pat ‘582 in view of Dimitrov et al., Schlothauer et al., and Thompson et al., as evidenced by UnitProt entry P01857, Bao et al., and Hardwick et al. and further in view of Tiberghien et al. for the same reasons discussed in the Office Action mailed 7/11/2025.
Applicant’s arguments and amendments, filed 12/04/2025, have been fully considered, but have been found to be not convincing.
Applicant has argued that the instantly claimed invention has unexpected superior results over the prior art, however that has been found to be not convincing for the reasons discussed in the 35 U.S.C.§ 103 rejection supra.
Therefore, the invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by Pat ‘582 in view of Dimitrov et al., Schlothauer et al., and Thompson et al., as evidenced by UnitProt entry P01857, Bao et al., and Hardwick et al., and further in view of Tiberghien et al.
Claims 16 and 17 stand as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 10,604,582 (Pat '582, supra) in view of Dimitrov et al. (supra), Schlothauer et al. (supra) and Thompson et al. (supra), as evidenced by UnitProt entry P01857 (supra), Bao et al. (supra), and Hardwick et al. (supra), as applied to claims 1-8 and 13-17 above, and further in view of Vogus et al. (J Control Release. 2017 Dec 10;267:191-202. doi: 10.1016/j.jconrel.2017.08.016. Epub 2017 Aug 18, in Office Action mailed 7/11/2025, supra).
The invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by Pat ‘582 in view of Dimitrov et al., Schlothauer et al., and Thompson et al., as evidenced by UnitProt entry P01857, Bao et al., and Hardwick et al. and further in view of Vogus et al. for the same reasons discussed in the Office Action mailed 7/11/2025.
Applicant’s arguments and amendments, filed 12/04/2025, have been fully considered, but have been found to be not convincing.
Applicant has argued that the instantly claimed invention has unexpected superior results over the prior art, however that has been found to be not convincing for the reasons discussed in the 35 U.S.C.§ 103 rejection supra.
Therefore, the invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by Pat ‘582 in view of Dimitrov et al., Schlothauer et al., and Thompson et al., as evidenced by UnitProt entry P01857, Bao et al., and Hardwick et al., and further in view of Vogus et al.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MAHER M HADDAD/Primary Examiner, Art Unit 1641