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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 28th, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 Summary
Claims 1-8 and 11-17 have been amended. Claims 1-17 are pending. Claims 1-17 are under examination and discussed in this Office action.
Drawings
The drawings are objected to because Figures 2B and 2C as presented in the drawings are the same graph showing MammaPrint Low risk patients, where in the specification Figure 2C is described as a graph showing MammaPrint High risk patients. Figure 2C should be replaced with the appropriate graph.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
Table 1 lacks a column header for the column that is presumably SEQ ID NOs. This objection is with reference to the most recently filed substitute specification, filed July 19th, 2024.
Appropriate correction is required.
Claim Objections
Claims 13, 15, and 16 are objected to because of the following informalities:
Claim 13 recites “six year” at the end of the claim. An “s” should be added to the end of the word “year”.
Claim 15 recites “…low risk of recurrence if they are typed as…high risk of recurrence if they are typed as…”. “They” appears to be referring to “the cancer”, but reads as if it is referring to the individual introduced in claim 9. Given the reference to “the cancer”, it is suggested both instances of “they are” be replaced with “it is” for clarity.
Claim 16 is missing a period at the end of the claim. This should be added.
Appropriate correction is required.
Claim Interpretation
The claims recite methods of treating a hormone receptor (HR)-positive breast cancer in an individual. The term “individual” can mean a number of different organisms without a limiting definition. Turning to the specification, the Applicant has provided a limiting definition of “individual” on Page 6: “As is used herein, the term “individual” refers to a human.” Given this definition, an individual will be interpreted as a human throughout this Office Action.
Claim Rejections - 35 USC § 112(b)
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 1-17 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.
Claims 1, 6, 8, 9, 15 and 17 recite some variation of “…said cancer is typed as having a low/high/ultra-low risk of recurrence…”. The terms “low risk”, “ultra-low risk”, and “high risk” in the claims are relative terms which render the claims indefinite. The terms are not defined by the claims, the specification does not provide a definitive 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. These relative terms make determining risk of recurrence indefinite because it is unclear how “low risk”, “ultra-low risk”, or “high risk” is being defined. Furthermore, while claims 6, 8, 15, and 17 define “low risk”, “ultra-low risk”, and “high risk” through the use of the MammaPrint test, there is still no clarity presented on how this test defines “low risk”, “ultra-low risk”, and “high risk”. Claims 2-5, 7, 10-15, and 16 are also rejected here for their dependence on either claim 1 or claim 9 and not further clarifying the identified issue. For the purpose of compact prosecution, the broadest reasonable interpretation of “low risk”, “ultra-low risk”, and “high risk” as they are defined in the prior art will be applied.
Claims 5, 6, 8, 14, 15, and 17 contain the trademark/trade name MammaPrint. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the breast cancer 70-gene signature test (e.g. MammaPrint, see page 11 of the specification) and, accordingly, the identification/description is indefinite.
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.
Claims 1-4, 7-13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Sparano (Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer, The New England Journal of Medicine, June 2018, 379, 112-121, and protocol included as supplemental material), as evidenced by Moore (Oncotype DX Risk Recurrence Score and Total Mortality for Early-Stage Breast Cancer by Race/Ethnicity, Cancer Epidemiology, Biomarkers, and Prevention, April 2022, 31, 821-830).
Regarding instant claim 1, Sparano teaches a method of treating a hormone receptor (HR)-positive breast cancer in an individual (Page 112, column 1, paragraph 2), comprising administering endocrine therapy to the individual, wherein said cancer is typed as having a recurrence score of 10 or lower (Page 112, column 2, paragraph 3). As evidenced by Moore, a 21-gene recurrence score of 10 or lower as defined by Sparano is considered a low risk of recurrence (Page 821, column 2, paragraph 2: “A recent randomized trial, Trial Assigning Individualized Options for Treatment (TAILORx), used revised ODX RS cutoffs of low-risk (<11), intermediate-risk (11–25), and high-risk (>25) groups…”).
Sparano does not directly teach wherein said cancer is typed as having a low risk of recurrence and wherein said endocrine therapy is administered for more than five years. However, Sparano does teach that individuals with a low risk of recurrence are assigned to receive endocrine therapy (e.g. hormonal therapy) only (Page 112, column 2, paragraph 3; associated trials protocol provided as supplementary material, Page 22, Treatment Arms, Secondary Study Group-1). Sparano further teaches that the endocrine therapy may be chosen by the treating physician from guidelines provided in Appendix III (associated trials protocol provided as supplementary material, Page 22, Treatment Arms). Turning to Appendix III, treatment options include tamoxifen or letrozole for years 1-5 of treatment in Regimens A or C, followed by an aromatase inhibitor in Regimens 2 or 4 for years 6-10 (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens). As defined in the instant specification, all are considered endocrine therapy (see Page 6 of the instant specification). Given these guidelines, it would be obvious to one of ordinary skill in the art that a cancer typed as having a low risk of recurrence may be administered endocrine therapy for more than 5 years as this would amount to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)).
Regarding instant claim 2, Sparano teaches the method according to claim 1. Sparano further teaches wherein the endocrine therapy comprises an aromatase inhibitor and/or anti-oestrogen therapy (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens). As defined in the instant specification, an aromatase inhibitor may be letrozole (see Page 6 of the instant specification) and an anti-oestrogen therapy may be tamoxifen (see Page 2 of the instant specification).
Regarding instant claim 3, Sparano teaches the method according to claim 1. Sparano further teaches wherein the endocrine therapy comprises letrozole and/or tamoxifen (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens).
Regarding instant claim 4, Sparano teaches the method according to claim 1. Sparano further teaches wherein the endocrine therapy has a duration of at least six years (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens).
Regarding instant claim 7, Sparano teaches the method according to claim 1. Sparano further teaches wherein the individual is a post-menopausal woman (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens).
Regarding instant claim 8, Sparano teaches the method according to claim 1. Sparano further teaches wherein the cancer is not typed as MammaPrint ultralow risk (MP-UL) (Page 112, column 1, paragraph 2: “On the basis of the 21-gene recurrence score…). Sparano does not teach on MammaPrint typing, and therefore will not type the cancer as MammaPrint ultralow risk (MP-UL).
Regarding instant claim 9, Sparano teaches a method of treating an individual with hormone receptor (HR)-positive breast cancer with endocrine therapy if said cancer is typed as having a recurrence score of 10 or lower (Page 112, column 2, paragraph 3) and treating an individual with HR-positive breast cancer with endocrine therapy if said cancer is typed as having a recurrence score of 26 or higher (Page 112, column 2, paragraph 3). As evidenced by Moore, a 21-gene recurrence score of 10 or lower as defined by Sparano is considered a low risk of recurrence and a 21-gene recurrence score of 26 or higher as defined by Sparano is considered a high risk of recurrence (Page 821, column 2, paragraph 2: “A recent randomized trial, Trial Assigning Individualized Options for Treatment (TAILORx), used revised ODX RS cutoffs of low-risk (<11), intermediate-risk (11–25), and high-risk (>25) groups…”).
Sparano does not directly teach treating an individual with hormone receptor (HR)-positive breast cancer with endocrine therapy administered for more than five years if said cancer is typed as having low risk of recurrence. Sparano also does not directly teach treating an individual with HR-positive breast cancer with endocrine therapy administered for five years or less if said cancer is typed as having high risk of recurrence. However, Sparano does teach that individuals with low risk of cancer recurrence are assigned to receive endocrine therapy (e.g. hormonal therapy) only (Page 112, column 2, paragraph 3; associated trails protocol provided as supplementary material, Page 22, Treatment Arms, Secondary Study Group-1). Sparano also teaches teach that individuals with high risk of cancer recurrence are assigned to receive endocrine therapy (e.g. hormonal therapy) and chemotherapy (Page 112, column 2, paragraph 3; associated trials protocol provided as supplementary material, Page 22, Treatment Arms, Secondary Study Group-2). Sparano further teaches that the endocrine therapy in both instances may be chosen by the treating physician from guidelines provided in Appendix III (associated trials protocol provided as supplementary material, Page 22, Treatment Arms). Turning to Appendix III, treatment options include tamoxifen or letrozole for years 1-5 of treatment in Regimens A or C, followed by an aromatase inhibitor in Regimens 2 or 4 for years 6-10 (associated trails protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens). As defined in the instant specification, all are considered endocrine therapy (see Page 6 of the instant specification). Treatment options also include tamoxifen or letrozole for years 1-5 of treatment in Regimens A or C, with subsequent stoppage of treatment for years 6-10 in Regimens 1 or 3 (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens). Given these guidelines, it would be obvious to one of ordinary skill in the art that an individual with hormone receptor (HR)-positive breast cancer can be treated with endocrine therapy for more than five years if said cancer is typed as having low risk of recurrence a cancer, and further that an individual with HR-positive breast cancer can be treated with endocrine therapy for five years or less if said cancer is typed as having high risk of recurrence. This would amount to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)).
Regarding instant claim 10, Sparano teaches the method of treating according to claim 9. Sparano further teaches wherein the endocrine therapy administered for more than five years comprises an aromatase inhibitor and/or anti-oestrogen therapy (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens). As defined in the instant specification, an aromatase inhibitor may be letrozole (see Page 6 of the instant specification) and an anti-oestrogen therapy may be tamoxifen (see Page 2 of the instant specification).
Regarding instant claim 11, Sparano teaches the method of treating according to claim 9. Sparano further teaches wherein the endocrine therapy administered for more than five years comprises letrozole and/or tamoxifen (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens).
Regarding instant claim 12, Sparano teaches the method of treating according to claim 9. Sparano further teaches wherein the endocrine therapy administered for five years or less comprises an aromatase inhibitor and/or anti-oestrogen therapy (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens). As defined in the instant specification, an aromatase inhibitor may be letrozole (see Page 6 of the instant specification) and an anti-oestrogen therapy may be tamoxifen (see Page 2 of the instant specification).
Regarding instant claim 13, Sparano teaches the method of treating according to claim 9. Sparano further teaches wherein the endocrine therapy administered for more than five years has a duration of at least six year (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens).
Regarding instant claim 16, Sparano teaches the method of treating according to claim 9. Sparano further teaches wherein the individual is a post-menopausal woman (associated trials protocol provided as supplementary material, Appendix III, Hormonal Therapy Regimens).
Claims 5-6 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Sparano (Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer, The New England Journal of Medicine, June 2018, 379, 112-121, and protocol included as supplemental material), as applied to claims 1-4, 7-13, and 16 above, and further in view of Desai (MammaPrint for Individualized Recurrence Risk Assessment and Treatment Recommendations for Early-Stage Breast Cancer Patients, Handbook of Therapeutic Biomarkers in Breast Cancer, 2013, Chapter 14, 387-416).
Regarding instant claim 5, 6, 14, and 15, Sparano teaches the methods according to claims 1 and 9.
Sparano does not teach wherein the cancer is typed using MammaPrint, wherein the cancer is considered as having low risk of recurrence if it is typed as MammaPrint low risk (MP-L), or wherein the cancer is considered as having high risk of recurrence if they are typed as MammaPrint high risk (MP-H).
Desai, in the same field of endeavor, teaches wherein breast cancer may be typed using MammaPrint, wherein breast cancer is considered as having low risk of recurrence if it is typed as MammaPrint low risk (MP-L), and wherein breast cancer is considered as having high risk of recurrence if they are typed as MammaPrint high risk (MP-H) (Page 389, paragraph 1). Desai further teaches that hormone-receptor-positive breast cancer may be tested with MammaPrint (Page 398, Table 14.2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Sparano with the MammaPrint typing of Desai. Since both Sparano and Desai are in the same field of endeavor (e.g. molecular tests for breast cancer), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to simple substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). The MammaPrint test of Desai is functionally equivalent to the 21-gene test of Sparano as both determine risk of cancer recurrence by organizing patients into at least low and high risk groups. Furthermore, one of ordinary skill in the art would have been motivated to make this modification because the MammaPrint test has been clinically validated (Desai, Pages 389-390, Section 14.3).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Sparano (Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer, The New England Journal of Medicine, June 2018, 379, 112-121, and protocol included as supplemental material), as applied to claims 1-4, 7-13, and 16 above, and further in view of Esserman (Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades, JAMA Oncology, June 2017, 3, 1503-1510).
Regarding instant claim 17, Sparano teaches the method of treating according to claim 9.
Sparano does not teach wherein the individual with HR-positive breast cancer is treated with endocrine therapy administered for five years or less if said cancer is typed as having MammaPrint ultralow risk (MP-UL).
Esserman, in the same field of endeavor, teaches wherein an individual with HR-positive breast cancer typed as having MammaPrint ultralow risk (MP-UL) has a negligible risk of death with two or more years of treatment with tamoxifen (Page 1507, column 1, paragraph 2). This reasonably teaches that an individual with HR-positive breast cancer can be treated with endocrine therapy administered for five years or less if said cancer is typed as having MammaPrint ultralow risk (MP-UL).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Sparano with the MammaPrint typing and treatment of Esserman. Since both Sparano and Esserman are in the same field of endeavor (e.g. molecular tests for breast cancer), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because women typed as having MP-UL can have only 2 years of therapy and have excellent long-term survival (Esserman, Page 1507, column 1, paragraph 3).
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683