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 .
Application Status
The Preliminary amendment filed on 8/02/2024 is acknowledged. Claims 42-57 are currently pending and under consideration.
Information Disclosure Statement
The listing of references in the PCT international search report is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, “the list ... must be submitted on a separate paper.” Therefore, the references cited in the international search report have not been considered. Applicant is advised that the date of submission of any item of information in the international search report will be the date of submission of the IDS for purposes of determining compliance with the requirements for the IDS with 37 CFR 1.97, including all timing statement requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Interpretation
Claim 46 recites the limitation “…wherein the breast cancer is HER2-negative early stage (II-III) breast cancer. While the specification and prior art at the time of filing makes reference to HER2-negative early stage breast cancer, neither the specification or prior art specifically point to the factors, measurable or non-measurable, which make up HER2-negative early stage breast cancer. Since the claims make reference to “stage (II-III)”, the examiner is interpreting the stage to be consistent with for example, Stages of Breast Cancer as outlined by the National Cancer Institute (received on 1/21/2026). Accordingly, Stage II and Stage III is interpreted to also include Stage IIA-IIB and Stage IIIA and IIIB as these appear to fall under the general stage II and stage III.
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.
Claim 46 is 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.
The term “early stage (II-III)” in claim 46 is a relative term which renders the claim indefinite. The term “early stage” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The claim limitation for prior art purposes will be interpreted as set forth above.
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.
Claim(s) 42-45, 52 and 54-57 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Robson et al. (N. Engl. J. Med. 2017; 377:523-33) as evidenced by Lee et al. (Ann Lab. Med. 2020; 40: 114-121).
Robson et al. details a randomized, open-label phase 3 trial in which Olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease (abstract). With regards to Olaparib, Robson et al. teach that 300 mg Olaparib tablets twice daily were assigned to the patients (Abstract). Moreover, Robson et al. teach that Olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with Olaparib monotherapy than with standard therapy (Conclusions). While the prior art does not specifically teach that the germline BRCA1 and/or BRCA2 gene mutations are pathogenic or likely pathogenic, the claimed limitation appears to be taught because as evidenced by Lee et al. when referencing the study of Robson et al., “A phase III trial of Olaparib in metastatic breast cancer patients with HER2:BRCA pathogenic variants involved 302 patients….” (page 117, 1nst column, 2nd full paragraph). Additionally, while the prior art does not specifically teach the outcomes as recited in claims 55-56, the Examiner recognizes that the prior art appears to teach the administration of the same drug, in the claimed amount, to the same patients population. As such, it is reasonable to assume that such an outcome would be necessarily present. Applicants are reminded that the office does not have the facilities and resources to determine such outcomes. Burden is on Applicant so show that the result or outcome would not come to fruition applying the method of the prior art.
Claim(s) 42-46 and 54-57 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tutt et al. (Lancet 2010; 376: 235-244).
Tutt et al. assessed the efficacy, safety and tolerability of Olaparib alone in women with BRCA1 or BRCA mutations and advanced breast cancer (Summary, Background). With regards to the women, Tutt et al. teach that eligible women were aged 18 years or older and had locally advanced breast cancer or metastatic breast cancer (stage IIIB/IIIC), received at least one chemotherapy regimen and all patients were required to have a germline BRCA1 or BRCA2 mutation that was confirmed to be deleterious (page 234, 2nd column, Patients). In addition to the patients having a germline BRCA1 or BRCA2 mutation, Tutt et al. teach that the study also included patients that were HER2-negative (p 237, Table 1). Tutt et al. further teach that the clinical benefit rate was 52% for cohort 1 and 26% for cohort 2, wherein median progression-free survival was 5-7 months for cohort 1 and 3-8 months for cohort 2. Additionally, while the prior art does not specifically teach the outcomes as recited in claims 55-56, the Examiner recognizes that the prior art appears to teach the administration of the same drug to the same patients population. As such, it is reasonable to assume that such an outcome would be necessarily present. Applicants are reminded that the office does not have the facilities and resources to determine such outcomes. Burden is on Applicant so show that the result or outcome would not come to fruition by applying the method of the prior art.
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.
Claim(s) 53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Robson et al. (N. Engl. J. Med. 2017; 377:523-33) as evidenced by Lee et al. (Ann Lab. Med. 2020; 40: 114-121), as applied to claims 42-45, 52 and 54-57 above.
Robson et al. details a randomized, open-label phase 3 trial in which Olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease (abstract). With regards to Olaparib, Robson et al. teach that 300 mg Olaparib tablets twice daily were assigned to the patients (Abstract). Moreover, Robson et al. teach that Olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with Olaparib monotherapy than with standard therapy (Conclusions). While the prior art does not specifically teach that the germline BRCA1 and/or BRCA2 gene mutations are pathogenic or likely pathogenic, the claimed limitation appears to be taught because as evidenced by Lee et al. when referencing the study of Robson et al., “A phase III trial of Olaparib in metastatic breast cancer patients with HER2:BRCA pathogenic variants involved 302 patients….” (page 117, 1nst column, 2nd full paragraph). Additionally, while the prior art does not specifically teach the outcomes as recited in claims 55-56, the Examiner recognizes that the prior art appears to teach the administration of the same drug, in the claimed amount, to the same patients population. As such, it is reasonable to assume that such an outcome would be necessarily present. Applicants are reminded that the office does not have the facilities and resources to determine such outcomes. Burden is on Applicant so show that the result or outcome would not come to fruition applying the method of the prior art.
While Robson et al. teach administration of Olaparib to metastatic breast cancer patients with HER2:BRCA pathogenic variants, the prior art does not specifically teach over a period of a year.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to optimize the method taught by Robson et al. to at least 1 yr . One of ordinary skill in the art would have been motivated to make such an optimization, with a reasonable expectation of success, because:
-Robson et al. discusses the outcomes of a Phase III clinical trial, wherein the primary end point was progression-free survival and not longevity of its use
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claim(s) 46-49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Robson et al. (N. Engl. J. Med. 2017; 377:523-33) as evidenced by Lee et al. (Ann Lab. Med. 2020; 40: 114-121), as applied to claims 42-45, 52 and 54-57 above, in view of Tutt et al. (Lancet 2010; 376: 235-244).
Robson et al. details a randomized, open-label phase 3 trial in which Olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease and had received neoadjuvant or adjuvant treatment with an anthracycline and a taxane (abstract). With regards to Olaparib, Robson et al. teach that 300 mg Olaparib tablets twice daily were assigned to the patients (Abstract). Moreover, Robson et al. teach that Olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with Olaparib monotherapy than with standard therapy (Conclusions). While the prior art does not specifically teach that the germline BRCA1 and/or BRCA2 gene mutations are pathogenic or likely pathogenic, the claimed limitation appears to be taught because as evidenced by Lee et al. when referencing the study of Robson et al., “A phase III trial of Olaparib in metastatic breast cancer patients with HER2:BRCA pathogenic variants involved 302 patients….” (page 117, 1nst column, 2nd full paragraph). Additionally, while the prior art does not specifically teach the outcomes as recited in claims 55-56, the Examiner recognizes that the prior art appears to teach the administration of the same drug, in the claimed amount, to the same patients population. As such, it is reasonable to assume that such an outcome would be necessarily present. Applicants are reminded that the office does not have the facilities and resources to determine such outcomes. Burden is on Applicant so show that the result or outcome would not come to fruition applying the method of the prior art.
While Robson et al. teach administration of Olaparib to metastatic breast cancer patients with HER2:BRCA pathogenic variants which had received neoadjuvant or adjuvant treatment with an anthracycline and a taxane, the prior art does not specifically teach that the patient is HER2-negative early (Stage II-III) breast cancer or that the patient had completed definitive local treatment such as surgery and/or radiotherapy.
Tutt et al. assessed the efficacy, safety and tolerability of Olaparib alone in women with BRCA1 or BRCA mutations and advanced breast cancer (Summary, Background). With regards to the women, Tutt et al. teach that eligible women were aged 18 years or older and had locally advanced breast cancer (not amenable to curative surgery or radiation) or metastatic breast cancer (stage IIIB/IIIC), received at least one chemotherapy regimen and all patients were required to have a germline BRCA1 or BRCA2 mutation that was confirmed to be deleterious (page 234, 2nd column, Patients). In addition to the patients having a germline BRCA1 or BRCA2 mutation, Tutt et al. teach that the study also included patients that were HER2-negative (p 237, Table 1). Tutt et al. further teach that the clinical benefit rate was 52% for cohort 1 and 26% for cohort 2, wherein median progression-free survival was 5-7 months for cohort 1 and 3-8 months for cohort 2.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Robson et al. to include patients having HER2-negative early (Stage II-III) breast cancer or patients that had completed definitive local treatment such as surgery and/or radiotherapy in view of Tutt et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- Tutt et al. teaches a similar method of use of Olaparib and includes stage IIIB/C patients as well as those that had locally advanced breast cancer no amendable to curative surgery or radiation.
Claim(s) 50-51 is/are rejected under 35 U.S.C. 103 as being unpatentable over Robson et al. (N. Engl. J. Med. 2017; 377:523-33) as evidenced by Lee et al. (Ann Lab. Med. 2020; 40: 114-121), as applied to claims 42-45, 52 and 54-57 above, in view of Lee et al. (Ann Lab. Med. 2020; 40: 114-121).
Robson et al. details a randomized, open-label phase 3 trial in which Olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease and had received neoadjuvant or adjuvant treatment with an anthracycline and a taxane (abstract and patients). With regards to Olaparib, Robson et al. teach that 300 mg Olaparib tablets twice daily were assigned to the patients (Abstract). Moreover, Robson et al. teach that Olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with Olaparib monotherapy than with standard therapy (Conclusions). While the prior art does not specifically teach that the germline BRCA1 and/or BRCA2 gene mutations are pathogenic or likely pathogenic, the claimed limitation appears to be taught because as evidenced by Lee et al. when referencing the study of Robson et al., “A phase III trial of Olaparib in metastatic breast cancer patients with HER2:BRCA pathogenic variants involved 302 patients….” (page 117, 1nst column, 2nd full paragraph). Additionally, while the prior art does not specifically teach the outcomes as recited in claims 55-56, the Examiner recognizes that the prior art appears to teach the administration of the same drug, in the claimed amount, to the same patients population. As such, it is reasonable to assume that such an outcome would be necessarily present. Applicants are reminded that the office does not have the facilities and resources to determine such outcomes. Burden is on Applicant so show that the result or outcome would not come to fruition applying the method of the prior art.
While Robson et al. teach administration of Olaparib to metastatic breast cancer patients with HER2:BRCA pathogenic variants which had received neoadjuvant or adjuvant treatment with an anthracycline and a taxane, the prior art does not specifically teach that the patient has completed at least 6 cycles of neoadjuvant or adjuvant chemotherapy.
Lee et al. teach that while BRCA1 pathogenic variant cells are somewhat resistant to microtubule-inhibiting chemotherapies, such as taxanes, in vitro, patients with ER-BRCA pathogenic variant breast cancer showed better pathological complete response than sporadic breast cancer patients when treated with anthracycline-taxane-based neoadjuvant chemotherapy compared with those who were treated with single anthracycline-based chemotherapy (page 117, 1st column, lines 4-9)
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Robson et al. to include patients having at least 6 rounds of anthracycline-taxane-based neoadjuvant chemotherapy in view of the teachings of Lee et al. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- Robson et al. includes in their study patients whom had received neoadjuvant or adjuvant treatment with an anthracycline and a taxane and found that Olaparib monotherapy provided a significant benefit; and
-Lee et al. teaches that anthracycline-taxane-based chemotherapy are typical first line neoadjuvant chemotherapies.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
-Caulfield et al. (J. Adv Pract Oncol 2019;10(2):167-174).
- US Food and Drug Administration (2018). FDA approves Olaparib for germline BRCA-mutated metastatic breast cancer.
-Kudos Pharmaceuticals (WO2004/080976A1. 2004-09-23).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626