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 .
Status of the Claims
Applicant’s submission filed 07 August 2026 has been entered. Claims 1-8, 10, 16-19, and 21 are pending. Claims 1-3, 10, 18, and 21 have been amended, while claims 9, 11-14, and 20 have been cancelled without prejudice or disclaimer. Therefore, prosecution on the merits continues for claims 1-8, 10, 16-19, and 21.
Status of Prior Rejections/Response to Arguments
RE: Objection to claims 1, 10, and 12
The cancellation of claim 12 renders the objection of that claim moot. For the remaining claims, Applicant’s amendments to each of instant claims 1 and 10 obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 12-14 and 20 under 35 USC 102(a)(1) and 35 USC 102(a)(2) over Sachs et al
The cancellation of each of instant claims 12-14 and 20 renders the rejection of record moot for those claims.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-11, 16-17, and 21 under 35 USC 103 over Scheel et al in view of Sachs et al
The cancellation of claims 9 and 11 renders the rejection of record moot for those claims. For
the remaining claims, Applicant's arguments filed 07 August 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 8-10 of the Remarks filed 07 August 2026 that the present invention allows for the construction of a multicellular breast organoid from luminal progenitor cells, wherein the specific growth conditions within the luminal progenitor cells in vitro results in low-grade invasive processes of mammary cancer. In response, the Examiner respectfully submits that Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Applicant has further traversed the rejection, asserting in Page 10 of the Remarks filed 07 August 2026 that the disclosure of Scheel et al does not teach how to create a multicellular breast organoid from luminal progenitor cells, and instead specifically teaches a method of determining the rate of spontaneous de-differentiation of luminal progenitor cells. In response, the Examiner respectfully submits that Scheel et al do disclose the formation of multicellular organoids that morphologically and/or functionally resemble a terminal ductal-lobular unit that comprise luminal mammary progenitor cells. See, for example, Paragraphs [0105]-[0109] of Scheel et al.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
RE: Rejection of claims 1-11, 16-18, and 21 under 35 USC 103 over Scheel et al in view of Sachs et al, and further in view of Srivastava et al
The cancellation of claims 9 and 11 renders the rejection of record moot for those claims. For the remaining claims, Applicant's arguments filed 07 August 2026 have been fully considered but they
are not persuasive.
Applicant has traversed the rejection, asserting in Pages 11-12 of the Remarks filed 07 August 2026 that the disclosure of Srivastava et al fails to teach a multicellular breast organoid unit that morphologically and functionally recapitulates low-grade invasive processes of low-grade carcinoma of no special type from luminal progenitor cells. In response, the Examiner respectfully submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Srivastava et al is a tertiary reference relied upon to teach that mammary organoid models of invasive ductal carcinoma exist, wherein the mammary organoids comprise luminal cells. Therefore, the ordinary artisan would have recognized that the multicellular organoids of Scheel et al comprising luminal progenitor cells can serve as a model for low-grade invasive ductal carcinoma given the teachings of Srivastava et al.
Therefore, the rejection is maintained.
RE: Rejection of claims 1-11, 16-17, 19, and 21 under 35 USC 103 over Scheel et al in view of Sachs et al, and further in view of Amin et al
The cancellation of claims 9 and 11 renders the rejection of record moot for those claims. For the remaining claims, Applicant's arguments filed 07 August 2026 have been fully considered but they
are not persuasive.
Applicant has traversed the rejection, asserting in Page 12 of the Remarks filed 07 August 2026 that the ordinary artisan would not have had a reasonable expectation of success in translating the 2D quiescence morphology of Amin et al to the 3D organoid duct elongation arrest as instantly claimed. In response, the Examiner respectfully submits that the person of ordinary skill in the art would have reasonably expected that the MCF7 luminal breast cancer cells of Amin et al in 2D culture would respond the same as in a 3D mammosphere culture of Amin et al, and could be applied to the multicellular breast cancer organoids of Scheel et al comprising luminal progenitor cells. Accordingly, the cell elongation arrest observed within the 2D culture of MCF7 luminal breast cancer cells can be reasonably translated to the multicellular breast organoids of Scheel et al. The Examiner would also like to note that it is not required that the expectation of success be a certainty; only one that is reasonable to a person of ordinary skill. In re Longi, 759 F.2d 887, 897 (Fed. Cir. 1985) (“Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness”).
Therefore, the rejection is maintained.
Maintained Grounds of Rejection
Claim Interpretation
Under the broadest reasonable interpretation of each claim, all of the “optional” limitations are not required.
In addition, Applicant has described a representative number of epidermal growth factor “analogues” in Paragraph [0069] of the instant disclosure. Such “analogues” include transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-8, 10, 16-17, and 21 remain rejected under 35 U.S.C. 103 as being unpatentable over Scheel et al (US 2018/0155686 A1, of record on IDS filed 26 February 2024) in view of Sachs et al (US 2017/0342385 A1, of record).
Scheel et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Sachs et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 1, 3-5, and 16: Scheel et al disclose methods of generating multicellular organoids that morphologically and/or functionally resemble a terminal ductal-lobular unit (Abstract).
As such, Scheel et al disclose culturing human mammary luminal progenitor cells in a collagen gel comprised within a culture medium for at least seven days, and then determining whether a multicellular breast organoid unit is formed (Paragraphs [0010]-[0011], [0023], [0065], [0105], [0109], [0112], [0114]-[0116], [0129], [0157], [0162], [0167]-[0181]). Scheel et al further disclose that the mammary luminal progenitor cell breast organoid morphologically and functionally serves as a preclinical model of invasive breast cancer (Paragraphs [0008]-[0009], [0113], [0167], [0180]-[0181]).
Scheel et al further disclose that the culture medium comprises a ROCK inhibitor and fetal calf serum (Paragraphs [0118], [0120]-[0122], [0172], [0178], [0183], [0190]).
Scheel et al further disclose that the multicellular breast organoid is responsive to EGF (Paragraphs [0127], [0143], [0180]).
Scheel et al do not disclose that the culture medium comprises one or more growth factors, as required by instant claim 1.
Sachs et al, however, disclose improved culture methods for expanding epithelial stem cells and obtaining organoids, and culture media involved in said methods (Abstract).
As such, Sachs et al disclose the culture of a breast organoid comprising luminal cells in a culture media comprising serum, a ErbB3/4 ligand, FGF7 and/or FGF10, a Wnt agonist, B27, N-acetylcysteine, Nicotinamide, a ROCK inhibitor, SB202190, and EGF (Paragraphs [0037]-[0045], [0051]-[0081], [0120]-[0136], [0165]-[0166], [0174]-[0175], [0263], [0272]-[0273], [0276]).
Therefore, it would have been prima facie obvious to have modified the method of Scheel et al such that the culture medium further comprises EGF, as detailed in Sachs et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to include EGF in the culture medium, as it is beneficial for growth of breast organoids (Sachs et al: Paragraph [0124]), and would have had a reasonable expectation of success given that the disclosures of Scheel et al and Sachs et al are concerned with the generation of organoids derived from mammary tissue. See MPEP § 2143(I)(G).
Consequently, Scheel et al as modified by Sachs et al render obvious a method of forming a multicellular organoid unit that morphologically and/or functionally resembles a terminal ductal-lobular unit that can be used as a preclinical model of invasive breast cancer, wherein human mammary luminal progenitor cells (claim 3) are cultured in a collagen gel comprised within a culture medium for at least seven days, and then determining whether a multicellular organoid unit is formed. As the culture medium comprises EGF (claims 4, 16), a ROCK inhibitor (claim 5), and fetal calf serum, this therefore renders obvious the method of instant claim 1.
Regarding claim 2: Following the discussion of claim 1, Scheel et al further disclose that determining whether a multicellular organoid unit is formed is by determining whether ductal structures and multiple branch-points are comprised within the multicellular organoid unit (Paragraphs [0012], [0023], [0111], [0124]-[0126], [0130], [0140], [0165]). This therefore reads on the method of the instant claim.
Regarding claim 6: Following the discussion of claim 1, Scheel et al further disclose that the culture medium comprises Pen/Strep, which are antibiotics (Paragraphs [0183], [0190]). This therefore reads on the method of the instant claim.
Regarding claims 7 and 17: Following the discussion of claim 1, Scheel et al further disclose that the luminal progenitor cells are genetically modified, wherein the cells comprise a knockout of one or more genes (claim 17) (Paragraphs [0109]-[0111], [0141]). This therefore reads on the method of the instant claim. This therefore reads on the method of instant claim 7.
Regarding claim 8: Following the discussion of claim 1, Scheel et al further disclose that the collagen gel has a concentration of 0.5 to 2 mg/ml (Paragraph [0115]). This therefore reads on the method of the instant claim. See MPEP § 2131.03.
Regarding claim 10: Following the discussion of claim 1, Scheel et al further disclose that the luminal progenitor cell organoid is utilized for testing drug compounds, including those associated with cell migration (Paragraphs [0143], [0180]). As the testing involves measuring a cellular response of the luminal progenitor cells comprised within the organoid, wherein the cellular response includes cell proliferation, growth arrest, apoptosis, necrosis, DNA damage, differentiation, de-differentiation, trans-differentiation, and changes in the morphology of cells in the multicellular structure (Paragraph [0180]), this therefore reads on the method of the instant claim.
Regarding claim 21: Following the discussion of claim 1, Scheel et al further disclose that the human mammary luminal progenitor cells are derived from a healthy subject (Paragraphs [0023], [0113], [0179], [0183]). This therefore reads on the method of the instant claim.
Claims 1-8, 10, 16-18, and 21 remain rejected under 35 U.S.C. 103 as being unpatentable over Scheel et al (US 2018/0155686 A1, of record on IDS filed 26 February 2024) in view of Sachs et al (US 2017/0342385 A1, of record), and further in view of Srivastava et al (Curr Opin Cell Biol, 2020, of record).
The discussion of Scheel et al as modified by Sachs et al regarding claim 1 can be observed
above and is relied upon herein, the content of which is incorporated in its entirety. Scheel et al as modified by Sachs et al render obvious claims 1-8, 10, 16-17, and 21. Srivastava et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 18: As aforementioned in the discussion of claim 1 above, Scheel et al disclose that the mammary luminal progenitor cell organoid morphologically and functionally serves as a preclinical model of invasive breast cancer.
The combination of Scheel et al and Sachs et al fail to teach that the mammary luminal progenitor cell organoid recapitulates low-grade invasive processes of low-grade carcinoma of no special type, as required by instant claim 18.
Srivastava et al, however, disclose mammary organoid models of invasive ductal carcinoma comprising luminal cells (Pages 1-2, 4-5; Figures 1-3).
Therefore, it would have been prima facie obvious to have modified the method of Scheel et al in view of Sachs et al such that the mammary luminal progenitor cell organoid morphologically and functionally recapitulates low-grade invasive ductal carcinoma, which is synonymous with low-grade carcinoma of no special type, as detailed in Srivastava et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to model low-grade carcinoma of no special type, and would have had a reasonable expectation of success given that the mammary luminal progenitor cell organoids of Scheel et al are capable of serving as models of invasive breast cancer. See MPEP § 2143(I)(G).
Consequently, Scheel et al as modified by Sachs et al and Srivastava et al render obvious a method of forming a mammary luminal progenitor cell organoid unit that morphologically and/or functionally recapitulates the invasive processes associated with low-grade carcinoma of no special type. This therefore renders obvious the method of the instant claim.
Claims 1-8, 10, 16-17, 19, and 21 remain rejected under 35 U.S.C. 103 as being unpatentable over Scheel et al (US 2018/0155686 A1, of record on IDS filed 26 February 2024) in view of Sachs et al (US 2017/0342385 A1, of record), and further in view of Amin et al (Molecular Oncology, 2016, of record).
The discussion of Scheel et al as modified by Sachs et al regarding claims 1 and 10 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Scheel et al as modified by Sachs et al render obvious claims 1-8, 10, 16-17, and 21. Amin et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 19: Following the discussion of claim 10 above, Scheel et al further disclose that the cellular response includes cell proliferation, growth arrest, apoptosis, necrosis, DNA damage, differentiation, de-differentiation, trans-differentiation, and changes in the morphology of cells in the multicellular structure (Paragraph [0180]).
The combination of Scheel et al and Sachs et al fail to teach that the cellular response includes cell elongation arrest, as required by instant claim 19.
Amin et al, however, disclose that the contacting of a mammary organoids with a migration-related compound results in the arrested elongation of the mammary cells within the organoid (Pages 577-578, 580, 585; Figures 1, 5).
Therefore, it would have been prima facie obvious to have modified the screening method of Scheel et al in view of Sachs et al such that the measured cellular response is an arrested cell elongation, as detailed in Amin et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to investigate the morphological and proliferative changes as result of an introduced compound, and would have had a reasonable expectation of success given that the disclosures of Scheel et al and Amin et al are concerned with the analysis of cellular responses elicited from mammary organoids. See MPEP § 2143(I)(G).
Consequently, Scheel et al as modified by Sachs et al and Amin et al render obvious a method of screening for an anti-migratory drug, wherein the measured cellular response is an arrested cellular elongation. This therefore renders obvious the method of the instant claim.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
