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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-2, 7-9, 11, 13-15, 18, 21-22) in the reply filed on 02/26/2026 is acknowledged.
The Restriction Requirement is made Final.
Claims 1-2, 7-9, 11, 13-15, 18, 21-24, 26, 29-31, and 33 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Claims 23-24, 26, 29-31, and 33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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, and 21-22 have been examined on their merits.
Claim Objections
Claims 7, 18 and 22 are objected to because of the following informalities:
Claim 7 recites the term “TGFalpha” and for proper form this should be “TGF-alpha”.
Claim 18 contains a typo as the word “then” in line two should be spelled as “than”.
Claim 22 recites the abbreviation “ER”. According to Applicant’s Specification this means “estrogen receptor” (page 1 para 3).
An abbreviation should be preceded in its first occurrence by the specific identity of the entity which said abbreviation is intended to represent. Thereafter, the use of the abbreviation in the claims will be understood.
Appropriate correction is required.
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 14 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.
Claim 14 is dependent upon claim 1 which already requires that there are more luminal cells than non-luminal cells in a first population of organoids and then adds that the organoids are composed of 50% or more luminal cells. Since claim 14 allows for 50% luminal cells it then also allows for 50% non-luminal cells and this is a contradiction of parent claim 1 thus rendering the metes and bounds of claim 14 unclear and indefinite.
Appropriate correction is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 7-9, 11, 13-14, 21-22 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Sachs et al (WO 2016/083612-from IDS filed 12/20/2023).
Regarding claims 1-2, 11, 14, Sachs disclose a method of forming mammary organoids from isolated mammary epithelial cells comprising contacting the mammary epithelial cells with an organoid medium that contains a Wnt agonist, but is free from exogenously added BMP signaling and exogenously added sex hormone and then culturing in the organoid medium for a time sufficient to form a first population of organoids enriched for organoids composed of more luminal cells than non-luminal cells and wherein the organoid medium includes a basal medium (page 12 ) and an ErbB3/4 ligand (Erb4 ligand-neuregulin 1) (page 5 lines 1-25, pages 72-73, claims 1, 2, 19-21 and 24). The organoids comprise luminal cells but no basal cells (non-luminal cells) (page 74 claim 24).
Regarding claims 7-8, Sachs disclose further including amphiregulin in their organoid medium (page 73, claims 17, 19-21) which is a ligand of ErbB1 that is not EGF or TGF-alpha (page 26, lines 11-12).
Regarding claim 9, Sachs disclose using ErbB3/4 ligand which is a ligand of both the ErbB4 family and the ErbB3 family (different ErbB family) (page 72).
Regarding claim 13, Sachs disclose wherein the non-luminal cells are basal cells (page 74 claim 24).
Regarding claims 21-22, Sachs disclose wherein the organoids are contacted with an inhibitor of TGF-beta (page 73 claims 13, 15, 19-21) 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 also disclose further comprising nuclear localization of estrogen receptor (ER, estrogen receptor alpha (page 3 Figures 5 and 6).
Therefore, the teaching of Sachs et al anticipates Applicant’s invention as claimed.
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, 13-15, 18, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Sachs et al (WO 2016/083612-from IDS filed 12/20/2023) in view of Jarde et al (Nature Communications 2016).
Regarding claims 1-2, 7-9, 11, 13-14, and 21-22, Sachs disclose the limitations of these claims as described above and provide a motivation and reasonable expectation of success for their combination, thus also rendering them obvious.
Regarding claims 15 and 18, Sachs disclose that an organoid culture can be split to produce a new organoid culture (second population of organoids) (page 55 lines 25-28), 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 method of Sachs 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 start out with normal mammary organoids produced from culture conditions with basal medium, Wnt signaling agonist and neuregulin (ErbB4 ligand) and then Sachs provides 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 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 54-56).
Therefore, the combined teachings of Sachs et al and Jarde et al render obvious Applicant’s invention as claimed.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Sachs et al., “A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity”, Cell, 2018, Vol. 172, pp. 373-386.
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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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631