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 invention group 1, drawn to a method of producing a population of mammary gland cells, claims 1-4,13-21, in the reply filed on 6/18/2026 is acknowledged.
Claims 23-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species/invention.
Claim Status
Claims 1- 4, 13-21, 23-29 are pending
Claims 5-12 22, 30-35 are cancelled.
Claims 23-29 are withdrawn.
Claims 1-4, 13-21 are under examination.
Claim objection
.Claim 3 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim2. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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.
Claims 2-3 and 19-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite in that it fails to point out what is included or excluded by the claim language.
Claims 2-3 contain the trademark/trade name MammoCult. 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 culture medium and, accordingly, the identification/description is indefinite.
Claims 19 and 20 contain relative terms The term “increased” in claims 19 and 20 is a relative term which renders the claim indefinite. The term “increased” is not defined by the claims, the specification does not provide a 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. Therefore, the claims are 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 13-21 are rejected under 35 U.S.C. 103 as being unpatentable over Qu et al., Stem cell reports 8.2 (2017) and Micallef, et al., Stem Cell Research 1.1 (2007), as evidenced by Witkowska-Zimmy et al., 2017.
Regarding claim 1, Qu teaches a method of producing mammary gland cells from human induced pluripotent stem cells (hiPSCs) in a two -step protocol, wherein they first generated embryonic bodies (EBs) (introduction, page 205) or mEBS which were further cultured to generate mammary-like cells and organoids (abstract, introduction, page 205). Qu also teaches that bone morphogenic protein 4 (BM4) signaling plays an essential role in early embryonic mammary gland commitment (introduction, page 205).
Regarding claims 2 and 3, Qu teaches culturing hiPSCs in MammoCult media in 3D mixed floating/suspension cultures to direct iPSCs to differentiate towards non-neural ectoderm (fig 1A, Results, mEBs culture enriching Non-neural Ectoderm cells, page 207).
Regarding claim 4, Qu further teaches growing the formed mEBS embedded in 3D culture matrix (fig. 1A) and generating mammary epithelial cells with lactocyte markers such as CK18, and producing milk (figs. 4d and S3) which is a feature of lactocyte. CK18 is a lactocyte marker as evidenced by Witkowska-Zimmy et al., 2017.
Qu does not teach generating EBs in culture medium comprising bone BMP4 and retinoic acid (RA) from iPSCs.
However, before the effective filling date of the claimed invention, generating EBs form pluripotent cells in a culture medium containing BMP4 and RA was known in the art.
Regarding claim 1, Clement teaches culturing the mammary cell line MCF10A which has a similar gene expression profile to human primary mammary progenitors in the presence of BMP4 to generate mammary cell spheres, colonies and terminal duct tubular units and observed that BMP4 significantly increased the ability of MCF10A cells to form spheres (Results, page 156, fig.1b and fig.1f).
Clement does not teach culturing mammary spheres or EBs in the presence of RA.
However before the effective filling date of the claimed invention, culturing mammary epithelial cell clusters in the presence of RA was known in the art.
Montesano teaches growing mammary epithelial cells (J3B1, a non-tumorigenic murine mammary epithelial cell line, material and methods, page 4420) in the presence of RA, and observed that RA induced the formation of lumen-containing colonies or cysts in a concentration and time dependent manner (abstract, page 4419).
Regarding claims 2 and 3, Clement teaches culturing mammary cell spheres in culture media supplemented with BMP4 (Results, page 156, fig.1b and fig.1f)..
Regarding claim 4, Montesano teaches culturing murine mammary cells in a in collagen gel cast and treated with RA (Materials and methods, page 4420). .
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to combine the above-mentioned teachings of Qu, Clement and Montesano, to develop a method to produce mammary gland cells from hiPSCs as taught by Qu and improve the method by adding BMP4 and RA as taught by Clement and Montesano respectively. One of ordinary skill in the art would have been motivated to supplement the MammoCult media generating EBs in Qu with BMP4 in Clement to promote mammary spheres/ EBs formation, and with RA taught by Montesano to facilitate lumen formation in mammary EBs. There would be a reasonable expectation of success to combine the teachings of Qu with Clement and Montesano because they all teach generating 3D mammary bodies.
Regarding claim 13, Clement teaches adding BMP4 to the culture medium in a concentration 15 ng/ml (Results, page 156, fig.1).
Regarding claim 14, Montesano teaches adding RA to the culture medium in a concentration 1 µM (material and methods, page 4420).
However one of ordinary skill in the art would recognize that the concentration of RA to be used in the culture medium is a result effective variable and the optimizing for the said concentration would be matter of routine optimization. Please see MPEP 2144.05 II routine optimization.
Regarding claim 15, Qu teaches EBs expressing one or more mammary gland positive progenitor markers (fig.3 D, page 210). Mammary gland positive progenitor markers are not defined in the specification. Therefore it is interpreted as mammary cell markers. However examples of said markers are recited in the specification such as EpCam which is also shown in Qu et al., fig. 3D.
Regarding claim 16, this claim has conditional language that does not further limit the claimed method of producing a population of mammary gland cells, such as not treating EBs with BMP4 and RA do not further limit the claimed method. Therefore, the instant claim does not carry patentable weight.
Regarding claim 17, Qu teaches the presence of multiple cell populations of mammary gland lineage in the EBs that were categorized into luminal-like, myoepithelial-like colonies depending on the expression of mammary positive markers (page 211), fig 4E of Qu shows 50% of luminal-like colonies and over 30% of myoepithelial-like colonies. Therefore, Qu teaches the requisite limitations of instant claim.
Regarding claims 18 and 19, Qu teaches the expression of α- lactalbumin and milk proteins (fig 3D). Increased expression recited in claim 19 is a relative term which is not given patentable weight (see 112b rejection).
Regarding claim 20, Qu teaches the presence of milk in what appears as lumens in their EBs (fig. S3), indicating secretion of milk/milk proteins.
Regarding claim 21, Qu teaches formation of mammary- like organoids (abstract) and mammary epithelial cells expressing lactocyte markers such as CK18, CSN2(beta-casein), and produce milk (figs. 4 and S3). Therefore Qu reads on requisite limitations of the instant claim
Hence, the claimed invention as a whole was prima facie obvious.
Conclusion
No claim is allowed.Any inquiry concerning this communication or earlier communications from the examiner should be directed to HASHANTHI ABEYRATNE-PERERA whose telephone number is (571)272-6562. The examiner can normally be reached Monday-Friday 7:30 am- 5:00pm.
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/HASHANTHI KOMITIGE ABEYRATNE-PERERA/ Examiner, Art Unit 1632
/MARCIA S NOBLE/ Primary Examiner, Art Unit 1632
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