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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/15/2026 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 24-25, 28-42, and 44-45 have an effective filing date of 05 JUN 2019.
Election/Restriction
In the response filed on 2/21/2025, Applicant elected:
Group II, claims 24-25, and 28-29
Status of Claims
Claims 24-25, 28-42, and 44-45 are currently pending and presented for examination on the merits.
Claims 24 and 28 are amended.
Claim 45 is new.
Claims 1-23, 26-27, and 43 are canceled.
Rejections Withdrawn
The rejection filed under 35 U.S.C. 112(a) is withdrawn in view of Applicant’s amendments to claims.
Rejections Maintained
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.
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 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 24-25, 28, 31-32, 35-41, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2012073047 A2, IDS 6/23/2022), and further in view of Roberts et al (Proteomic analysis of selected prognostic factors of breast cancer, Proteomics 2004, 4, 784–792, IDS 6/23/2022).
In regards to claims 24 and 28, Liu et al teaches mammillary epithelial is composed of two cell types luminal and myoepithelial cells [2nd paragraph, pg. 19]. Liu et al further teaches both cells arise from a multi-potent progenitor or stem cell population [2nd paragraph, pg. 19]. Liu et al further teaches BCL1 1a is expressed in luminal progenitors [Supplementary Fig. 7, pg. 2]. Liu et al further teaches BCL1 1a is a marker of mammary stem cells and a marker of basal breast cancer [1st paragraph, pg. 3]. Liu et al further teaches over-expression of BCL1 1a correlates with low survival and drives the terminal differentiation of basal breast cancer cells [1st paragraph, pg. 2]. Liu et al further teaches that BCL1 1a can be targeted for the treatment of breast cancer [1st paragraph, pg. 3]. Liu et al further teaches BCL1 1a can be used to diagnosis and prognosis of breast cancer [1st paragraph, pg. 3]. Liu et al further teaches the use of an inhibitor of BCL1 1a to prevent or treat breast cancer [Statements of invention, line 3, pg. 1]. Liu et al further teaches BCL1 1a is required for luminal progenitors from which some basal breast cancers are thought to originate [Example 1, 1st paragraph, pg. 19]. Liu et al further teaches abnormal BCL1 1a expression in aberrant luminal progenitors give advantages in survival and self-renewal, which account for some basal breast cancers [1st paragraph, pg. 31].
Liu et al does not specifically teach species associated with aberrantly differentiated cells are selected from a milk protein, a DNA molecule that codes for a milk protein and an RNA molecule that codes for a milk protein. However, this deficiency is made up in the teachings of Roberts et al.
Roberts et al teaches β-Casein is a protein that is produced by myoepithelial cells and secreted during lactation into milk [3.4 β-Casein, pg. 789].
Applicant states on pg. 3 of Specification, “beta-casein (CSN2)”.
Roberts et al teaches analysis revealed β-Casein in 22 forms in non-lactating breast tumor tissue [Left column, 2nd paragraph, pg. 790]. Roberts et al further teaches isoform 4 as a prognostic indicator in breast cancer [Left column, 2nd paragraph, pg. 790]. Roberts et al further teaches using tumor samples from lumpectomy or mastectomy [2.1 Materials and methods, pg. 785].
One of ordinary skill, before the effective filing date, would have been motivated to combine Liu’s method of detecting markers of differentiated cells and treating, with Robert’s method of detecting CSN2, a milk protein, as a progenitor marker for breast cancer from a sample. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Liu and Robert’s methods for a method of treating a subject for breast cancer comprising analyzing a sample for a species associated with aberrantly differentiated cells of a milk protein and administer a treatment, because Liu and Roberts both teach methods of detecting and treating breast cancer.
In regards to claim 25, Liu et al teaches chemotherapy for tumor treatments [3rd Paragraph, pg. 30]. Furthermore, Roberts et al teaches using tumor samples from lumpectomy or mastectomy [2.1 Materials and methods, pg. 785].
In regards to claim 31, Liu et al teaches the use of Western Blot analysis [2nd Paragraph, pg. 36]. Furthermore, Roberts et al teaches analyzing the proteins in silver stain were those that the antibodies bound in the Western Blot [2.4 Image analysis, pg. 768].
In regards to claim 32, Roberts et al teaches using tumor samples from lumpectomy or mastectomy [2.1 Materials and methods, pg. 785].
In regards to claim 35, Liu et al teaches detecting Gata-3 and Elf5 that are key transcription factors in luminal progenitors [2nd Paragraph, pg. 24].
In regards to claim 36, Liu et al teaches imaging for breast cancer and is capable of detecting cancerous cells [2nd Paragraph, pg. 15].
In regards to claim 37, Liu et al teaches detection by MRI, CT or ultrasound [2nd Paragraph, pg. 15].
In regards to claims 38-39, Liu et al teaches DNA fragments binding Bcl11a antibodies [1st Paragraph, pg. 22].
In regards to claim 40, Liu et al teaches individuals identified at risk of breast cancer [6th Paragraph, pg. 13]. Liu et al further teaches triple negative breast cancer [3rd Paragraph, pg. 30].
In regards to claim 41, Liu et al teaches breast cancer patients with BRCA1 mutations [5th Paragraph, pg. 30].
In regards to claim 44, Roberts et al teaches analysis revealed β-Casein in 22 forms in non-lactating breast tumor tissue [Left column, 2nd paragraph, pg. 790]. Roberts et al further teaches isoform 4 as a prognostic indicator in breast cancer [Left column, 2nd paragraph, pg. 790].
Claims 24-25, 28-42, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2012073047 A2, IDS 6/23/2022), Roberts et al (Proteomic analysis of selected prognostic factors of breast cancer, Proteomics 2004, 4, 784–792, IDS 6/23/2022) as applied to claims 24-25, 28, 31-32, 35-41, and 44 above, and further in view of Chen et al (US 20170145515 A1, previous OA).
The teachings of Liu et al and Roberts et al are discussed above.
Liu et al does not specifically teach chemotherapeutic agents, sample via needle, and a non-pregnant subject. However, these deficiencies are made up in the teachings of Chen et al.
In regards to claims 29-30, Chen et al teaches screening for breast cancer [0004]. Chen et al further teaches determining a treatment regimen [0005]. Chen et al further teaches therapeutic agents comprising doxorubicin, epirubicin, paclitaxel, docetaxel, or a combination thereof [0005].
In regards to claim 33, Chen et al teaches diagnosing hyperplasia by needle biopsy [0018].
In regards to claim 34, Chen et al teaches collecting intraductal fluid and undergoing cytological examination [0142]. Chen et al further teaches analyzing blood for circulating markers [0154].
In regards to claim 42, Chen et al teaches collecting samples from non-pregnant subjects [0138].
One of ordinary skill, before the effective filing date, would have been motivated to combine Liu’s method of detecting markers of differentiated cells and treating, with Robert’s method of detecting CSN2, a milk protein, as a progenitor marker for breast cancer from a sample, with Chen’s method of detecting breast cancer in non-pregnant subjects by needle biopsy and treating by administering a anthracycline or taxane. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Liu, Roberts, and Chen’s for a method of treating a subject for breast cancer comprising analyzing a sample for a species associated with aberrantly differentiated cells of a milk protein and administer a treatment, because Liu, Roberts, and Chen all teach methods of detecting and treating breast cancer.
Claims 24-25, 28, 31-32, 35-41, and 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2012073047 A2, IDS 6/23/2022), Roberts et al (Proteomic analysis of selected prognostic factors of breast cancer, Proteomics 2004, 4, 784–792, IDS 6/23/2022) as applied to claims 24-25, 28, 31-32, 35-41, and 44 above, and further in view of Rosen et al (CSNAP Is a Stoichiometric Subunit of the COP9 Signalosome, Cell Reports, 13, 585–598, October 20, 2015).
The teachings of Liu et al and Roberts et al are discussed above.
Liu et al does not specifically teach alpha S1-casein (CSN1S1) and kappa-casein (CSN3). However, this deficiency is made up in the teachings of Rosen et al.
In regards to claim 45, Rosen et al teaches COP9 signalosome (CSN) complex contains eight subunits CSN1 through CSN8 [Left column, 1st paragraph, pg. 585]. Rosen et al further teaches the expression level of CSN subunits CSN1 and CSN3 in different cancers, including infiltrating duct carcinoma [Figure S5, pg. 6 of Supplemental]. Rosen et al further teaches the expression patterns in a range of cancers reported induce overexpression of the entire CSN complex [Right column, 3rd paragraph, pg. 594].
One of ordinary skill, before the effective filing date, would have been motivated to combine Liu’s method of detecting markers of differentiated cells and treating, with Robert’s method of detecting CSN2, a milk protein, as a progenitor marker for breast cancer from a sample, with Rosen’s method of detecting overexpression of CSN1, CSN3, and all CSN subunits in breast cancer. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Liu, Roberts, and Rosen’s methods for a method of treating a subject for breast cancer comprising analyzing a sample for a species associated with aberrantly differentiated cells of a milk proteins CSN1 and CSN3 and administer a treatment, because Liu and Roberts both teach methods of detecting and treating breast cancer. Furthermore Roberts and Rosen teach the detection of milk proteins, specifically CSN complex subunits.
Applicant’s Arguments:
Applicant respectfully traverses these rejections.
Roberts does not teach that β-casein is an effective marker for breast cancer. Rather, Roberts plainly indicates that the status of β-casein as a marker of breast cancer remains uncertain, disputed and unproven.
"opinion is divided between those who believe it is significant and those who believe that there is no correlation". Notably, Roberts explains that: "The inclusion of β-casein in this study was pursued because... the role of β-casein in non-lactating cells is currently unknown and the significance of its presence in breast cancer is in dispute"(page 785, col 1, para 3, emphasis added).
Roberts does not teach or suggest any specific link between p-casein and TNBC; a cancer type which is not mentioned at all in Roberts.
Examiner’s Response:
Applicant states, “Roberts does not teach that β-casein is an effective marker for breast cancer”.
Roberts et al teaches analysis revealed β-casein in 22 forms in non-lactating breast tumor tissue [Left column, 1st paragraph, pg. 790, and Figure 4]. Roberts et al further teaches that isoform 4 is a prognostic indicator in breast cancer [Left column, 1st paragraph, pg. 790]. Roberts et al further teaches that other isoforms showed little difference from healthy levels for the protein and explains why there is conflicting ideas surrounding whether β-casein is a potential prognostic marker [Left column, 1st paragraph, pg. 790].
Applicant states, “Roberts does not teach or suggest any specific link between β -casein and TNBC”.
Applicant’s Specifications states on pgs. 12-13, active surveillance is particularly useful for subjects who have been identified as being at risk of developing breast cancer (e.g. triple negative breast cancer), such as, for example, subjects who have a mutation of the BRCA1 and/or BRCA2 gene, or a family history of breast cancer, or who subjects who is homologous recombination deficient.
Applicant’s Specification states on pg. 11, In some embodiments, the subject is a subject who has been identified as being at risk of developing triple negative breast cancer. Thus, suitably, the subject is one who has one or more risk factors commonly associated with breast cancer (e.g. TNBC). Risk factors may include, for example, a family history of breast cancer, pains or discomforts of the breast, atypical growths on or around the breast, swelling or enlargement of one or both breasts, dense breast tissue, mutation of the BRCA1 and/or BRCA2 gene, and homologous recombination deficient. Suitably, the subject is one who has a mutation of the BRCA1 and/or BRCA2 gene, and most suitably, a mutation of the BRCA1 gene.
Applicant claim 40 states, “is a subject who has been identified as being at risk of developing triple negative breast cancer”. Applicant outlines risk factors for TNBC as the same as breast cancer, “risk factors commonly associated with breast cancer (e.g. TNBC). Risk factors may include, for example, a family history of breast cancer, pains or discomforts of the breast, atypical growths on or around the breast, swelling or enlargement of one or both breasts, dense breast tissue, mutation of the BRCA1 and/or BRCA2 gene, and homologous recombination deficient”[Specs, pg. 11].
Liu et al teaches risk factors for breast cancer include those with a family history of cancer [6th paragraph, pg. 13]. Liu et al further teaches BRCA1 mutations in breast cancer patients [5th paragraph, pg. 30].
One of ordinary skill would use Liu et al identified risk factors for developing TNBC such as family history, atypical growth of breast cancer, and testing for BRCA1 gene.
Conclusion
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642