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 .
This action is responsive to papers filed 07/07/2026.
Claims 1-2, 7-8, 14, 18, and 22 have been amended. Claim 39 has been newly added and no claims have been newly canceled.
Claims 1-2, 7-9, 11, 13-15, 18, 21-24, 26, 29-31, 33, and 39 are currently pending.
Claims 23-24, 26, 29-31, and 33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/26/2026.
Claims 1-2, 7-9, 11, 13-15, 18, 21-22 and 39 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claim(s) 1-2, 7-9, 11, 13-14, 21-22 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Sachs et al (GB 2532814A-hereinafter “Sachs ‘814”, newly cited) in view of Huguet et al (Cancer Research, 1994-newly cited).
Regarding claims 1, 7-8, 14, 39, Sachs ’814 disclose a method of forming mammary organoids from isolated mammary epithelial cells comprising contacting the mammary epithelial cells with an organoid medium containing an ErbB3/4 ligand (ErbB4 ligand)(pages 72-74). In one embodiment the culture medium consists of basal medium and an ErbB3/4 ligand such as neuregulin β-1 (ErbB4 ligand)(page 39 lines 5-24). A culture medium that consists of basal medium and a ligand of ErbB3/4 will be free of a Wnt agonist. Sachs ‘814 disclose that adding an ErbB3/4 ligand to the culture medium can result in a higher percentage of luminal cells and a lower percentage of basal cells (non-luminal cells) being present in the resultant organoid and in some embodiments predominantly comprise luminal cells and is substantially free of basal cells (page 70 lines 10-15). The addition of amphiregulin (a ligand of ErbB1 that is not EGF or TGF-alpha and is also a receptor tyrosine ligand) is also suggested (page 23).
Sachs ‘814 do not specifically exclude a Wnt agonist from all their organoid mediums, but do specifically indicate that a Wnt agonist “may” be included and is thus an optional addition to their culture media (page 16 lines 7-8). Sachs ‘814 indicate that in some cases the cells being cultured constitutively activate the Wnt pathway or secrete a Wnt agonist and would thus not require a Wnt agonist (page 16 lines 8-12, lines 24-25).
Huguet disclose that Wnt gene expression was investigated in human breast cancer, nontumorous breast tissue and a variety of human breast cell lines (abstract) In general, mammary cells are shown to express Wnt (page 2615 column 2, page 2620 column 2 and Table 2).
One of ordinary skill in the art would have been motivated to culture the mammary cells in the method of Sachs ‘814 without an exogenous-added Wnt signaling agonist because Sachs ‘814 indicate that this addition is optional especially in cases where the cells already constitutively express Wnt and Huguet teach that mammary cells naturally express Wnt protein (an endogenous WNT signaling agonist), thus suggesting that a Wnt agonist is not needed for mammary cell cultures in the method of Sachs ‘814. One of ordinary skill in the art would have had a reasonable expectation of success because Huguet demonstrate that mammary cells secrete Wnt protein (a Wnt agonist) (page 2615 column 2, page 2620 column 2 and Table 2).
Regarding claim 2, Sachs ‘814 disclose that their organoid medium optionally contains an inhibitor of BMP signaling (abstract, page 14 lines 24-32, page 15). The BMP inhibitor will likely result in more proliferative organoids than if the BMP inhibitor is absent (page 15 lines 1-2).
Regarding claim 9, Sachs ‘814 disclose using ErbB3/4 ligand which is a ligand of both the ErbB4 family and the ErbB3 family (different ErbB family) (page 72-74).
Regarding claim 11, Sachs ‘814 disclose wherein the organoid medium is free of exogenously added sex hormones, such as progestin or estradiol (page 40 lines 18-21). In addition, progesterone is indicated as an optional additive and thus embodiments free of this added sex hormone are also suggested (page 14 lines 3-5).
Regarding claim 13, Sachs ‘814 disclose wherein the non-luminal cells are basal cells (page 70 lines 10-15).
Regarding claims 21-22, Sachs ‘814 disclose wherein the organoids are contacted with an inhibitor of TGF-beta (abstract, pages 23-24) and this inherently provides nuclear localization of ER according to Applicant’s Specification (page 3 para 21, page 20 para 119, pages 25-26 para 149). Sachs ‘814 also disclose further comprising nuclear localization of estrogen receptor (ER, estrogen receptor alpha (page 3 Figures 5 and 6).
Therefore, the combined teachings of Sachs ‘814 and Huguet et al render obvious Applicant’s invention as claimed.
Claim(s) 15 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Sachs et al (GB 2532814A-hereinafter “Sachs ‘814”, newly cited) in view of Huguet et al (Cancer Research, 1994-newly cited) as applied to claims 1-2, 7-9, 11, 13-14, 21-22 and 39 above, and further in view of Jarde et al (Nature Communications 2016).
Regarding claims 1-2, 7-9, 11, 13-14, 21-22 and 39, Sachs ‘814 and Huguet render obvious these claims as described above.
Regarding claims 15 and 18, Sachs ‘814 disclose that an organoid culture can be split to produce a new organoid culture (second population of organoids) (page 81 lines 17-33), but do not specifically describe using a modified organoid medium with a second population of organoids.
Jarde disclose methods of developing in vitro culture systems for mammary organoids (abstract). Neuregulin and R-spondin allow maintenance and expansion of mammary organoids (abstract).
Alternative culture conditions are described in Jarde that promote enrichment of basal cells organized in multiple layers surrounding a keratinous core, reminiscent of structures observed in MMTV-Wnt1 tumours. These conditions comprise a unique tool that should further understanding of normal mammary gland development, the molecular mechanism of hormone action and signaling events whose deregulation leads to breast tumourigenesis (abstract, pages 4-5, establishment of mammary cultures that resemble Wnt1 tumours, Figure 3). A basal culture medium containing R-spondin (Wnt agonist), Noggin (BMP inhibitor) and EGF is used to promote the growth of mammary organoids that are enriched for basal cells (pages 5-7). The core of the non-transformed mammary structures from these culture conditions resembled typical squamous metaplasia observed in mammary tumour tissues (page 7 column 1). Use of this in vitro culture system can serve as an instrumental tool for investigating mammary gland biology, in addition for potential drug screening applications (page 10 column 2).
One of ordinary skill in the art would have been motivated to use this alternative culture condition of basal medium supplemented with EGF, a WNT signaling agonist (R-spondin) and an inhibitor of BMP (Noggin) in the organoid splitting method of Sachs ‘814 because Jarde suggest that this will allow for the production of populations of organoids that can be further used as tools for investigating mammary gland biology and potential drug screening applications. These culture conditions provide mammary organoids with more basal cells and fewer luminal cells than if one or both of the Wnt agonist and BMP inhibitor are not added as taught by Jarde. Both Jarde and Sachs ‘814 start out with normal mammary organoids produced from culture conditions with basal medium and neuregulin (ErbB4 ligand) and then Sachs ‘814 provide the conditions that will allow for the production of secondary organoids that promote enrichment of basal cells organized in multiple layers surrounding a keratinous core, reminiscent of structures observed in MMTV-Wnt1 tumours. One of ordinary skill in the art would have had additional motivation and a reasonable expectation of success because Sachs ‘814 also indicates that using their organoids for clinical and research applications such as disease research and drug screening is desirable and beneficial as well (pages 81-82).
Therefore, the combined teachings of Sachs ‘814, Huguet et al and Jarde et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant’s arguments, see pages 7-8, filed 07/07/2026, with respect to the rejection(s) of claim(s) 1-2, 7-9, 11, 13-15, 18, 21-22 and 39 under Sachs et al (WO 2016/083612) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Sachs et al (GB 2532814-newly cited) and Huguet et al as described above.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Jones et al., “ErbB4 Signaling in the Mammary Gland Is Required for Lobuloalveolar Development and Stat5 Activation during Lactation”, The Journal of Cell Biology, 1999, Volume 147, Number 1, pp. 77–87.
(Jones disclose in vivo evidence demonstrating a role for ErbB4 signaling in terminal differentiation of mammary epithelial cells (page 85).)
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 LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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