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 .
Claim Interpretation
Claims 1, 3, 4, 7-12, and 14-16 are drawn to methods of treating early triple negative breast cancer (eTNBC). Applicant’s definition of eTNBC includes stage I-III TNBC; see page 16 lines 10-13 of the instant Specification. It is noted that locally advanced cancer includes patients with stage III breast cancer; see Kumar Garg et al. (Current Onocology. 22(5): e409-e410: Published: October 2015) left column. Thus, the methods of claims 1, 3, 4, 7-12, and 14-16 encompass treating a subset of patients with locally advanced TNBC. Similarly, claims 17-24 recite a method for treating operable TNBC. Locally advanced breast cancer is divided into operable and inoperable. Thus, the method of claims 17-24 encompasses treating a subset of patients with locally advanced TNBC.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11 and 23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11 depends from claim 10, which recites that the subject is previously untreated for eTNBC. Claim 11 recites that the subject has not received (i) a prior systemic therapy for treatment or prevention of breast cancer; (ii) a previous therapy with anthracyclines or taxanes for any malignancy; or (iii) a prior immunotherapy. It is unclear if only one of items (i)-(iii) needs to be met to meet the claim or all of items (i)-(iii) need to be met. For example, if the subject has received a prior immunotherapy, but not received a prior systemic therapy for treatment or prevention of breast cancer nor a previous therapy with anthracyclines or taxanes for any malignancy, is this subject within the scope of the claim?
Similarly, claim 23 recited that the subject is previously untreated for the operable TNBC; and/or has not received (i) a prior systemic therapy for treatment or prevention of breast cancer; (ii) a previous therapy with anthracyclines or taxanes for any malignancy; or (iii) a prior immunotherapy. Claim 23 suffers from the same indefiniteness as claim 11. And further, in claim 23, it appears that the subject could have previously treated operable TNBC so longer as the subject has not receive one of items (i)-(iii).
For the purpose of compact prosecution, claims 11 and 23 are interpreted as the subject needing to only have not received a single one of items (i)-(iii).
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 7, 8, 10, 11, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schmid et al. (The New England Journal of Medicine. 382: 810-821; Published: February 27, 2020) as evidenced by the instant Specification.
Regarding claims 1, 4, 7, 8, 10, and 11, Schmid et al. teaches treating patients with untreated early, or stage II or stage III, triple negative breast cancer (TNBC) with a neoadjuvant combination of pembrolizumab, paclitaxel, and carboplatin Q3W for four cycles followed by pembrolizumab plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide for an additional four cycles; see Abstract. Regarding claim 12, 83.7% of patients treated with the pembrolizumab combination had a PD-L1 positivity score of 1 or greater.
Regarding the clause “wherein the treatment regimen increases the subject’s likelihood of having a pathologic complete response (pCR) as compared to treatment with the taxane, the anthracycline, and the alkylating agent without the anti-PD-L1 antibody or the anti-PD-1 antibody” in claim 1, this outcome is necessarily the natural result of the combination of elements explicitly disclosed by the prior art. The claim requires only the single step of administering the claimed regimen comprising the combination of a taxane, an anthracycline, an alkylating agent, and either an anti-PD-L1 or anti-PD-1 antibody in the neoadjuvant setting. Given that the claim does not recite any additional steps necessary to bring about the result of increased likelihood of pCR, the result is a natural result which necessarily flows from the step of administering. Moreover, this is evidenced by the instant Specification page 114 lines 6-8, which teaches that the 57.6% of the patients receiving an anti-PD-L1/anti-PD-1 antibody + chemotherapy achieved pCR compared to 41.1% the patients receiving placebo+ chemotherapy.
Thus, Schmid et al. anticipates claims 1, 4, 7, 8, 10, 11, and 12.
Claims 1, 4, 7, 8, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pusztai et al. (San Antonio Breast Cancer Symposium. 80(Supplement 4): PD1-01; Published: February 15, 2020) as evidenced by the instant Specification.
Regarding claims 1, 4, 7, and 8, Pusztai et al. teaches treating patients with stage I-III triple negative breast cancer (TNBC) with a neoadjuvant combination of durvalumab and nab-paclitaxel followed by durvalumab plus doxorubicin-cyclophosphamide (ddAC); see Background. Regarding claim 12, 38% of patients treated had a PD-L1 positivity score of 1& or greater; see Methods and Results.
Regarding the clause “wherein the treatment regimen increases the subject’s likelihood of having a pathologic complete response (pCR) as compared to treatment with the taxane, the anthracycline, and the alkylating agent without the anti-PD-L1 antibody or the anti-PD-1 antibody” in claim 1, this outcome is necessarily the natural result of the combination of elements explicitly disclosed by the prior art. The claim requires only the single step of administering the claimed regimen comprising the combination of a taxane, an anthracycline, an alkylating agent, and either an anti-PD-L1 or anti-PD-1 antibody in the neoadjuvant setting. Given that the claim does not recite any additional steps necessary to bring about the result of increased likelihood of pCR, the result is a natural result which necessarily flows from the step of administering. Moreover, this is evidenced by the instant Specification page 114 lines 6-8, which teaches that the 57.6% of the patients receiving an anti-PD-L1/anti-PD-1 antibody + chemotherapy achieved pCR compared to 41.1% the patients receiving placebo+ chemotherapy.
Thus, Pusztai et al. anticipates claims 1, 4, 7, 8, and 12.
Claims 17-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ignatiadis et al. (Cancer Research. 79(Supplement 4): OT3-05-02; Published: February 15, 2019) as evidenced by the clinical trial listing for NCT03498716 (ClinicalTrials.gov; Published: April 23, 2018).
Claims 17-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ignatiadis et al. (Annals of Oncology. 30(5): 289TiP; Published: October 2019) as evidenced by the clinical trial listing for NCT03498716 (ClinicalTrials.gov; Published: April 23, 2018).
The following analysis is applicable to both rejections over the teachings of Ignatiadis et al. (Cancer Research. 79(Supplement 4): OT3-05-02; Published: February 15, 2019) as evidenced by the clinical trial listing for NCT03498716 (ClinicalTrials.gov; Published: April 23, 2018) and Ignatiadis et al. (Annals of Oncology. 30(5): 289TiP; Published: October 2019) as evidenced by the clinical trial listing for NCT03498716 (ClinicalTrials.gov; Published: April 23, 2018).
Regarding claims 17-20 and 24, Ignatiadis et al. teaches treating patients with untreated operable early, or stage II or stage III, triple negative breast cancer (TNBC) with an adjuvant combination of atezolizumab plus paclitaxel for 12 weeks followed by atezolizumab plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide for 8 weeks; see Abstract. Regarding claim 21, Ignatiadis et al. teaches administering atezolizumab 840 mg Q2W plus paclitaxel 80 mg/m2 QW for 12 weeks followed by atezolizumab 840 mg Q2W plus epirubicin 90 mg/m2 or doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 Q2W for 8 weeks. Regarding claim 22, Ignatiadis et al. teaches that atezolizumab 1200 mg Q3W is given as a maintenance regimen.
Regarding claim 23, Ignatiadis et al. is silent to the inclusion and exclusion criteria regarding prior treatment, but Ignatiadis et al. indicates that the trial taught is the clinical trial NCT03498716; see the final sentence of the Methods section or the Clinical trial identification line. The exclusion criteria for clinical trial NCT03498716 evidences that patients with previous systemic anti-cancer treatment or previous therapy with anthracyclines or taxanes for any malignancy are excluded.
Regarding the clause “wherein the treatment regimen effectively extends the subject’s invasive disease-free survival (iDFS) as compared to treatment with the taxane, the anthracycline, and the alkylating agent without the anti-PD-L1 antibody or the anti-PD-1 antibody” in claim 17, this outcome is necessarily the natural result of the combination of elements explicitly disclosed by the prior art. The claim requires only the single step of administering the claimed regimen comprising the combination of a taxane, an anthracycline, an alkylating agent, and either an anti-PD-L1 or anti-PD-1 antibody in the adjuvant setting. Given that the claim does not recite any additional steps necessary to bring about the result of extended iDFS, the result is a natural result which necessarily flows from the step of administering.
Thus, Ignatiadis et al., as evidenced by the clinical trial listing for NCT03498716, anticipates claims 17-24.
Claims 1, 3, 4, 7-11, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018), as evidenced by the instant Specification.
The following analysis is applicable to both rejections over the teachings of Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018), as evidenced by the instant Specification, and Mittendorf et al. (Annuals of Oncology. 28(Supplement 5): 212TiP; Published: September 2017), as evidenced by the instant Specification.
Regarding claims 1, 3, 4, 7, 8, 10, and 14, Mittendorf et al. teaches treating patients with untreated early, or stage II or stage III, triple negative breast cancer (TNBC) with a neoadjuvant combination of atezolizumab and nab-paclitaxel followed by atezolizumab plus doxorubicin-cyclophosphamide; see Methods. Regarding claim 9, the neoadjuvant combination comprises atezolizumab 840 mg Q2W and nab-paclitaxel 125 mg/m2 QW for 12 weeks followed by atezolizumab 840 mg Q2W plus doxorubicin-cyclophosphamide, 60 mg/m2 Q2W and 600 mg/m2 Q2W, respectively, for 8 weeks. Regarding claim 11, Mittendorf et al. teaches that exclusion criteria includes prior systemic therapy for the treatment or prevention of breast cancer or prior immunotherapy.
Regarding the clauses “wherein the treatment regimen increases the subject’s likelihood of having a pathologic complete response (pCR) as compared to treatment with the taxane, the anthracycline, and the alkylating agent without the anti-PD-L1 antibody or the anti-PD-1 antibody” and “wherein the treatment regimen increases the subject’s likelihood of having a pathologic complete response (pCR) as compared to treatment with nab-paclitaxel, doxorubicin, and cyclophosphamide without atezolizumab” in claims 1 and 14, this outcome is necessarily the natural result of the combination of elements explicitly disclosed by the prior art. The claim requires only the single step of administering the claimed regimen comprising the combination of a taxane, an anthracycline, an alkylating agent, and either an anti-PD-L1 or anti-PD-1 antibody in the neoadjuvant setting. Given that the claim does not recite any additional steps necessary to bring about the result of increased likelihood of pCR, the result is a natural result which necessarily flows from the step of administering. Moreover, this is evidenced by the instant Specification page 114 lines 6-8, which teaches that the 57.6% of the patients receiving atezolizumab + chemotherapy (nab-paclitaxel and doxorubicin + cyclophosphamide) achieved pCR compared to 41.1% the patients receiving placebo+ chemotherapy.
Thus, Mittendorf et al. anticipates claims 1, 3, 4, 7-11, and 14.
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.
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, 3, 4, 7-11, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018), as evidenced by the instant Specification, and in view of Schmid et al. (Journal of Oncology. 35(15): 556; Published: May 30, 2017).
The teachings of Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018) as related to claim(s) 1, 3, 4, 7-11, and 14, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither Mittendorf et al. reference teaches the use of carboplatin.
Regarding claims 15 and 16, Schmid et al. teaches that the addition of carboplatin to a neoadjuvant regimen comprising pembrolizumab, nab-paclitaxel, doxorubicin, and cyclophosphamide in patients with locally advanced, nonmetastatic TNBC improved overall response rate (ORR) and pathologic complete response (pCR).
It would have been obvious to one of ordinary skill in art to add carboplatin to the regimen taught by Mittendorf et al. comprising atezolizumab and nab-paclitaxel followed by atezolizumab plus doxorubicin-cyclophosphamide. One would have been motivated by the demonstration by Schmid et al. that the addition of carboplatin to a similar regimen, differing by the anti-PD-L1/anti-PD-1 agent used, resulted in improved overall response rate (ORR) and pathologic complete response (pCR). Given the favorable response findings by Schmid et al., one would have had a reasonable expectation of success that early TNBC patients can be treated with a regimen comprising atezolizumab, nab-paclitaxel, carboplatin, doxorubicin, and cyclophosphamide and that such a regimen would result in improved overall response rate (ORR) and pathologic complete response (pCR).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 1, 3, 4, 7-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018), as evidenced by the instant Specification, and in view of Pusztai et al. (San Antonio Breast Cancer Symposium. 80(Supplement 4): PD1-01; Published: February 15, 2020).
The teachings of Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018) as related to claim(s) 1, 3, 4, 7-11, and 14, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither Mittendorf et al. reference teaches that the subject treated has a PD-L1 score of 1% or greater.
Regarding claim 12, Pusztai et al. teaches a similar neoadjuvant regimen comprising an anti-PD-L1 antibody and chemotherapy in eTNBC. Pusztai et al. teaches determining PD-L1 positivity by IHC of pretreatment biopsies and defines PD-L1 positive at greater than 1% positive for PD-L1. Pusztai et al. finds that the rate of pCR is more than two-fold higher in PD-L1 positive patients compared to PD-L1 negative patients; see last sentence of Conclusion.
It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to use the neoadjuvant regimen taught by Mittendorf et al. comprising atezolizumab and nab-paclitaxel followed by atezolizumab plus doxorubicin-cyclophosphamide in patients with PD-L1 positivity greater than 1%. One would have been motivated by the findings of Pusztai et al., using a similar regimen of anti-PD-L1 antibody, nab-paclitaxel, doxorubicin, and cyclophosphamide in the same patient population and treatment setting as Mittendorf et al. that patients PD-L1 positivity achieved greater rates of pCR.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 1, 3, 4, 7-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018), as evidenced by the instant Specification, and in view of Schmid et al. (The New England Journal of Medicine. 379: 2108-2121; Published: October 20, 2018).
The teachings of Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018) as related to claim(s) 1, 3, 4, 7-11, and 14, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither Mittendorf et al. reference teaches that the subject treated has a PD-L1 score of 1% or greater.
Regarding claim 12, Schmid et al. teaches a similar regimen comprising an anti-PD-L1 antibody and chemotherapy in advanced TNBC. Schmid et al. teaches that the PD-L1 positive subgroup (PD-L1 >1%) achieved a greater median progression-free survival (PFS) and median overall survival (OS) and a higher rate of 1-year PFS and 2-year OS compared to the intent to treat population; see page 2110 right column and page 2114.
It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to use the neoadjuvant regimen taught by Mittendorf et al. comprising atezolizumab and nab-paclitaxel followed by atezolizumab plus doxorubicin-cyclophosphamide in patients with PD-L1 positivity greater than 1%. One would have been motivated by the favorable survival findings of Schmid et al., using a similar regimen of anti-PD-L1 antibody and nab-paclitaxel in TNBC patients.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the 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 17-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19 and 35 of copending Application No. 17/207,165 in view of Ignatiadis et al. (Cancer Research. 79(Supplement 4): OT3-05-02; Published: February 15, 2019) as evidenced by the clinical trial listing for NCT03498716 (ClinicalTrials.gov; Published: April 23, 2018), and Kumar Garg et al. (Current Onocology. 22(5): e409-e410: Published: October 2015).
Regarding instant claims 17, 18, 23, and 24, copending claims 19 and 20 teach a method of treating locally advanced or metastatic TNBC comprising administering atezolizumab plus nab-paclitaxel to a patient who is previously untreated for TNBC.
The copending claims of Application No. 17/207,165 do not state whether the treatment is neoadjuvant or adjuvant treatment nor do the copending claims teach adding and anthracycline and alkylating agent nor the specific dosing regimen.
Regarding instant claims 17-20 and 24, Ignatiadis et al. teaches treating patients with untreated operable early, or stage II or stage III, triple negative breast cancer (TNBC) with an adjuvant combination of atezolizumab plus paclitaxel for 12 weeks followed by atezolizumab plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide for 8 weeks; see Abstract. Regarding instant claim 21, Ignatiadis et al. teaches administering atezolizumab 840 mg Q2W plus paclitaxel 80 mg/m2 QW for 12 weeks followed by atezolizumab 840 mg Q2W plus epirubicin 90 mg/m2 or doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 Q2W for 8 weeks. Regarding instant claim 22, Ignatiadis et al. teaches that atezolizumab 1200 mg Q3W is given as a maintenance regimen.
Regarding instant claim 23, Ignatiadis et al. is silent to the inclusion and exclusion criteria regarding prior treatment, but Ignatiadis et al. indicates that the trial taught is the clinical trial NCT03498716; see the final sentence of the Methods section or the Clinical trial identification line. The exclusion criteria for clinical trial NCT03498716 evidences that patients with previous systemic anti-cancer treatment or previous therapy with anthracyclines or taxanes for any malignancy are excluded.
Regarding the clause “wherein the treatment regimen effectively extends the subject’s invasive disease-free survival (iDFS) as compared to treatment with the taxane, the anthracycline, and the alkylating agent without the anti-PD-L1 antibody or the anti-PD-1 antibody” in instant claim 17, this outcome is necessarily the natural result of the combination of elements explicitly disclosed by the prior art. The claim requires only the single step of administering the claimed regimen comprising the combination of a taxane, an anthracycline, an alkylating agent, and either an anti-PD-L1 or anti-PD-1 antibody in the adjuvant setting. Given that the claim does not recite any additional steps necessary to bring about the result of extended iDFS, the result is a natural result which necessarily flows from the step of administering.
Regarding the treatment setting, the instant disclosure defines eTNBC as stages I-III; see page 16 lines 10-13. The copending disclosure does it have a limiting definition for locally advanced TNBC, but states on page 15 that local advanced TNBC is usually stage II-III. Further, Kumar Garg et al. teaches that locally advanced breast includes patients with both operable or inoperable cancer.
It would have been obvious to one of ordinary skill in the art to modify the regimen taught by the copending claims to substitute nab-paclitaxel with paclitaxel and add doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. Because the treatment setting of locally advanced TNBC in the copending claims overlaps with the untreated, operable stage II or III TNBC in Ignatiadis et al. and because Ignatiadis et al. teaches an in progress clinical trial, one would have had a reasonable expectation of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 4, 7-12, and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19 and 35 of copending Application No. 17/207,165 in view of Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018), as evidenced by the instant Specification, and Werner et al. (Clinical Breast Cancer. 17(7): 503-509; Published: April 29, 2017).
Regarding instant claims 1, 3, 10-12, and 14, copending claims 19 and 20 teach a method of treating locally advanced or metastatic TNBC comprising administering atezolizumab plus nab-paclitaxel to a patient who is previously untreated for TNBC with a PD-L1 score >1%.
The copending claims of Application No. 17/207,165 do not state whether the treatment is neoadjuvant or adjuvant treatment nor do the copending claims teach adding and anthracycline and alkylating agent nor the specific dosing regimen.
Regarding instant claims 1, 3, 4, 7, 8, 10, and 14, Mittendorf et al. teaches treating patients with untreated early, or stage II or stage III, triple negative breast cancer (TNBC) with a neoadjuvant combination of atezolizumab and nab-paclitaxel followed by atezolizumab plus doxorubicin-cyclophosphamide; see Methods. Regarding instant claim 9, the neoadjuvant combination comprises atezolizumab 840 mg Q2W and nab-paclitaxel 125 mg/m2 QW for 12 weeks followed by atezolizumab 840 mg Q2W plus doxorubicin-cyclophosphamide, 60 mg/m2 Q2W and 600 mg/m2 Q2W, respectively, for 8 weeks. Regarding instant claim 11, Mittendorf et al. teaches that exclusion criteria includes prior systemic therapy for the treatment or prevention of breast cancer or prior immunotherapy.
Regarding the clauses “wherein the treatment regimen increases the subject’s likelihood of having a pathologic complete response (pCR) as compared to treatment with the taxane, the anthracycline, and the alkylating agent without the anti-PD-L1 antibody or the anti-PD-1 antibody” and “wherein the treatment regimen increases the subject’s likelihood of having a pathologic complete response (pCR) as compared to treatment with nab-paclitaxel, doxorubicin, and cyclophosphamide without atezolizumab” in instant claims 1 and 14, this outcome is necessarily the natural result of the combination of elements explicitly disclosed by the prior art. The claim requires only the single step of administering the claimed regimen comprising the combination of a taxane, an anthracycline, an alkylating agent, and either an anti-PD-L1 or anti-PD-1 antibody in the neoadjuvant setting. Given that the claim does not recite any additional steps necessary to bring about the result of increased likelihood of pCR, the result is a natural result which necessarily flows from the step of administering. Moreover, this is evidenced by the instant Specification page 114 lines 6-8, which teaches that the 57.6% of the patients receiving atezolizumab + chemotherapy (nab-paclitaxel and doxorubicin + cyclophosphamide) achieved pCR compared to 41.1% the patients receiving placebo+ chemotherapy.
It would have been obvious to one of ordinary skill in the art to modify the regimen taught by the copending claims to add doxorubicin-cyclophosphamide. One would have been motivated to add doxorubicin-cyclophosphamide to the treatment regimen because Werner et al. teaches that this chemotherapy combination in the neoadjuvant setting resulted in 100% complete response among TNBC patient and presented no unexpected toxicities; see Abstract. Because the treatment setting of locally advanced TNBC in the copending claims overlaps with the early stage II and III TNBC in Mittendorf et al. and because Mittendorf et al. teaches an in progress clinical trial, one would have had a reasonable expectation of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection.
Claims 15 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19 and 35 of copending Application No. 17/207,165 in view of Mittendorf et al. (Cancer Research. 78(Supplement 4): OT2-07-03; Published: February 15, 2018), as evidenced by the instant Specification, and Werner et al. (Clinical Breast Cancer. 17(7): 503-509; Published: April 29, 2017) as applied to claims 1, 3, 4, 7-12, and 14, and further in view of Schmid et al. (Journal of Oncology. 35(15): 556; Published: May 30, 2017).
The teachings of copending Application No. 17/207,165 in view of Mittendorf et al., as evidenced by the instant Specification, and Werner et al. as related to claim(s) 1, 3, 4, 7-12, and 14, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither the claims of copending Application No. 17/207,165, Mittendorf et al., nor Werner et al. teach the use of carboplatin.
Regarding instant claims 15 and 16, Schmid et al. teaches that the addition of carboplatin to a neoadjuvant regimen comprising pembrolizumab, nab-paclitaxel, doxorubicin, and cyclophosphamide in patients with locally advanced, nonmetastatic TNBC improved overall response rate (ORR) and pathologic complete response (pCR).
It would have been obvious to one of ordinary skill in art to add carboplatin to the regimen taught by the copending claims in view of Mittendorf et al. and Werner et al. comprising atezolizumab and nab-paclitaxel followed by atezolizumab plus doxorubicin-cyclophosphamide. One would have been motivated by the demonstration by Schmid et al. that the addition of carboplatin to a similar regimen, differing by the anti-PD-L1/anti-PD-1 agent used, resulted in improved overall response rate (ORR) and pathologic complete response (pCR). Given the favorable response findings by Schmid et al., one would have had a reasonable expectation of success that early TNBC patients can be treated with a regimen comprising atezolizumab, nab-paclitaxel, carboplatin, doxorubicin, and cyclophosphamide and that such a regimen would result in improved overall response rate (ORR) and pathologic complete response (pCR).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Schmid et al. (The Lancet. 21: 44-59; Published: November 27, 2019) teaches treating locally advanced or metastatic triple negative breast cancer with atezolizumab and nab-paclitaxel. Werner et al. (Clinical Breast Cancer. 17(7): 503-509; Published: April 29, 2017) teaches the combination of nab-paclitaxel, doxorubicin, and cyclophosphamide as a neoadjuvant in stage II and III breast cancer with particular efficacy in TNBC. Loibl et al. (Annals of Oncology. 30(Supplement 3): 122TiP; Published: May 2019) teaches treating patients with untreated early triple negative breast cancer (TNBC) with a neoadjuvant combination of atezolizumab, paclitaxel, and carboplatin followed by atezolizumab plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide for an additional four cycles; see Trial Design. Mittendorf et al. (Annuals of Oncology. 28(Supplement 5): 212TiP; Published: September 2017) teaches treating patients with untreated early, or stage II or stage III, triple negative breast cancer (TNBC) with a neoadjuvant combination of atezolizumab and nab-paclitaxel followed by atezolizumab plus doxorubicin-cyclophosphamide; see Methods.
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/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1646
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644