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 .
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.
Claim Status
Applicant’s arguments and amendments dated 7/16/26 have been received and entered in the application.
Claims 1-4, 6, 8-12, 15-16 are currently pending.
Claims 10-12 are withdrawn as directed to non-elected inventions.
Claims 1-4, 6, 8-9, 15-16 are elected and examined on the merits
Claims 6, 15 are currently amended.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
Preliminary Remarks
Claim 1 contains the status indicator “currently amended” . However, no mark-up is shown in the claim. As per MPEP § 714(II)(C) amendments to the claims must include markings to show the changes. In an attempt to advance prosecution despite the lack of mark-up, claim 1 is examined on the merits.
Specification
The use of the term MATRIGEL (MedSkin Solutions, Billerbeck, Germany) is a trade name or mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant’s proposed amendments do not include a markup of the specification as required by 37 CFR 1.121. Additionally, the proposed amendments do not include the required generic terminology. See MPEP 608.01(v).
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 1-4, 6, 8-9, 15-16 are 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.
The term “mammary-like” in claims 1 and 15 is a relative term which renders the claim indefinite. The term “mammary-like” is not defined by the claim, 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. The definition present in the specification relies upon another relative term (“simplified”) for the definition. Therefore, it is unclear what might constitute a mammary-like gland organoid.
Claim Rejections - 35 USC § 112(a)/1st paragraph
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Enablement
Claims 1-4, 6, 8-9, 15-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The specification, while being enabling for generating organoids containing lactocytes from human breast milk stem cells which secrete a milk-like product, does not reasonably provide enablement for production of a milk-like product other than lactoferrin, lactalbumin, C12:0, C16:0, C18:0, C18:1, C18:2, alpha-2-macroglobulin, inter-alpha-trypsin inhibitor heavy chain H2, or lactose (e.g., β-casein, β-lactoglobulin, etc.). The specification contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill:
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples;
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
(A) With respect to the breadth of the claims, the claims as currently drafted encompass generating mBSCs organoids containing lactocytes and inducing the lactocytes to secrete a mammalian milk-like product. The instant claims do not require any particular differentiation steps, culture conditions, or components to produce the organoids. Nor do the claims require any particular means for inducing the milk-like production. Consequently, the breadth of the claims is expansive.
(B) The invention is in the field of in vitro milk production.
(C)-(E) With respect to the state of the prior art, and predictability of the art, Majood et al., (2025) Human milk: insights on cell composition, organoids, and emerging applications. Pediatr Res, https://doi.org/10.1038/s41390-025-04458-3 (hereinafter Majood)., reviews the current state of the art with respect to human mammary organoid technology and milk production (Abstract, Introduction). Majood explains that there are limited protocols demonstrate methods for producing human mammary organoids from hBSCs with limited success in producing milk products (Advances in mammary organoid research, Table 1, Fig. 2). Generation of a mammary organoid requires isolation, proliferation, and spheroid culture with a growth and differentiation media (Advances in mammary organoid research, Table 1, Fig. 2). Induction of lactation requires supplementation with prolactin (Generation of lactating mammary organoids; “prolactin supplementation is a pivotal step for inducing lactation-specific functionality”). Therefore, in vitro milk production is an art with some degree of unpredictability.
(F)-(G) The applicants have provided a single working example directed to a method of producing a differentiated human mammary organoid. The working example indicates that the human mammary organoid secretes lactoferrin, lactalbumin, C12:0, C16:0, C18:0, C18:1, C18:2, alpha-2-macroglobulin, inter-alpha-trypsin inhibitor heavy chain H2, and lactose. The applicants have not provided any working examples directed to inducing milk production (as described by Majood), or any other milk-like products beyond those specifically recited above.
(H) Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the breadth of the claims, the state of the prior art and its lack of predictability, and the limited amount of guidance in the form of varied working examples in the specification.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1-4, 6, 8-9, 15-16, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 1-9 would not be enabled by the written disclosure. Therefore, claims 1-4, 6, 8-9, 15-16 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to make and/or use the invention commensurate with the present scope.
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 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, 8-9, 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hassiotou et al., (2012) Breastmilk is a novel source of stem cells with multilineage differentiation potential. Stem Cells, 30(10): 2164-2174 (cited on IDS dated 10/24/22, hereinafter Hassiotou).
Regarding claims 1, 15, Hassiotou discloses methods of producing mammary-like cells and organoids from a population of hBSCs (Abstract, Introduction) . Hassiotou discloses seeding hBSCs ultra-low binding culture and culturing for 2 to 3 weeks such that cell spheroids form (Cell culture, In vitro differentiation). The spheroids are subsequently transferred to a mammary differentiation media for an additional 3 to 4 weeks of culture (In vitro differentiation, 3D culture of breastmilk stem cells enriches for self-renewal ESC TFs, Differentiation of breastmilk stem cells into cells originating from the three germ layers, Fig. 3).
Hassiotou does not explicitly disclose inducing the lactocytes to secrete a mammalian milk-like product. However, Hassiotou discloses that fat globules form under mammary differentiation conditions, suggesting milk production may be possible (Fig. S7). Hassiotou further discloses that in some embodiments, the mammary spheroids secreted milk proteins, such as β-casein, lactoferrin, and α- lactalbumin, into the culture supernatant (Differentiation of breastmilk stem cells into cells originating from the three germ layers, Fig. 4). Therefore, there is a suggestion present in Hassiotou that the disclosed mammary organoids, at least in some embodiments, secrete a human milk-like product and milk proteins in accordance with the present claims.
Regarding claims 2, 8-9, Hassiotou discloses that the mammary organoids secrete milk proteins, such as β-casein, lactoferrin, and α- lactalbumin (Differentiation of breastmilk stem cells into cells originating from the three germ layers, Fig. 4).
Claim(s) 3-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hassiotou as applied to claims 1-2, 8-9 above and in further view of Gupta et al., US Publication No. 2017/0267970 (cited on IDS dated 10/24/22, hereinafter Gupta)
Regarding claim 3, Hassiotou does not disclose further treating the mammalian milk-like product to obtain a modified product. Regarding claim 4 Hassiotou does not disclose, that the treatment may comprise certain steps.
Gupta discloses methods of making hormone-responsive tissue, such as milk-producing mammary tissue and methods of producing milk (Abstract). Gupta discloses culturing mammary tissues in the presence of estrogen and progesterone for two weeks to produce a mature and hollow mammary-like tissue ([0182], [0377]). The addition of prolactin to the culture promotes formation of a lipid-rich, opaque substance within the luminal space ([0377]). In some embodiments, the disclosed cultures may be used to test agents for their ability to increase milk production ([0188]-[0191], [0379]). Gupta discloses that the amount of milk produced by the culture may be determined by any suitable means ([0183], [0187]).
As both Hassiotou and Gupta are directed to methods of culturing mammary organoid tissues it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to induce the mammary organoids of Hassiotou to produce milk according to the methods of Gupta as a use of a known technique to the method of Hassiotou to yield the predictable result of producing a milk.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hassiotou as evidenced by Considerations for efficient scale-up of PSCs in suspension culture. White Paper [online]. ThermoFisher, 2021 [retrieved on 2026-09-05]. Retrieved from the Internet: <https://assets.fishersci.com/TFS-Assets/BID/Reference-Materials/efficient-scale-pscs-suspension-culture-white-paper.pdf> (hereinafter, ThermoFisher).
Regarding claim 16, Hassiotou does not disclose that the hBSCs are cultured in a bioreactor. However, bioreactors are well-known alternatives for ultra-low adhesion culture plate suspension culture as evidenced by ThermoFisher. ThermoFisher reviews known techniques for suspension culture (Summary) ThermoFisher explains that suspension cultures may be performed in multiple types of vessel formats: small formats like 6-well plates and shaker flasks, and large-scale formats like spinner flasks and stirred bioreactors (Introduction and benefits). It would be obvious to one of ordinary skill in the art that the suspension culture of Hassioutou could be performed using any of the well-known means for suspension culture.
Response to Arguments
Applicant's arguments dated 7/16/26 have been fully considered but are not persuasive as explained in detail below.
Applicant argues that claims 15-16 were not rejected in the previous office action and should be considered allowable (Response p7).
As noted in the advisory action dated 8/3/26, claims 15-16 were not rejected due to a typographical error. The rejections of record were applicable to claims 15-16 as presented. Therefore, applicant’s arguments are not considered persuasive.
The specification is objected to for use of trade names or marks used in commerce.
Applicants argue that the specification has been amended to include the generic terminology and proper symbols to indicate trade names (Response p7-8).
MATRIGEL® is a registered trademark held by Discovery Labware, Inc. Appropriate correction is required. Additionally, the proposed amendments do not include a markup of the specification as required by 37 CFR 1.121.
Claims 1-4, 6, 8-9, 15-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite.
Applicant argues that the term “mammary-like” is sufficiently definite as per the definition provided in the specification at page 5 lines 9-12 (Response p11).
As noted in the rejection supra the definition provided at page 2 relies on a relative term (“simplified”) for the definition. The term “simplified” is not defined by the specification, nor does the specification provide a standard for ascertaining the requisite degree for what qualifies as “simplified”, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As the relative term relies upon a clear understanding of “simplified”, which is not provided by the specification, the term “mammary-like” is likewise indefinite for being a relative term.
Applicant argues that the term “simplified” is an art understood term indicating that the organoid does not possess the full complexity of the native tissue (Response p8).
While applicant may be correct that skilled artisans understand that “simplified” refers to an organoid that does not possess the full complexity of native tissue, the degree to which “simplification” is permitted by the present claims is unclear. That is, the claim language is relative.
Claims 1-4, 6, 8-9, 15-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
Applicant argues that the working examples were chosen because they are representative of well known bioactives found in milk (Response p9-10). Applicant argues that sampling performed indicated that standard human milk was produced (Response p9-10).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005. The issue at present is whether applicant has sufficiently demonstrated that other bioactives (e.g., β-casein, β-lactoglobulin, etc.), or milk itself, could be produced. As noted by the prior art, production of milk and milk-like products is a filed with some degree of unpredictability, and is dependent on the specific methodology utilized. As applicants have not provided any details as to how other bioactives or milk could successfully be produced beyond those specifically exemplified, it is not clear that the full scope of the claims presented is enabled by applicant’s disclosure.
Claim(s) 1-2, 8-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hassiotou.
Applicant argues that Hassioutou discloses methods of producing spheroids wherein the culture is only performed for up to 12 days (Response p11).
The section to which applicants point in support of this assertion, does not indicate that the culture occurred for only 12 days; it refers to a time period in which mRNA expression of the spheroids is analyzed (“[a] time-course analysis of OCT4, SOX2, and NANOG mRNA expression from day 1 to day 12 of spheroid formation revealed a stable upregulation of these genes”). To the contrary Hassiotou explicitly discloses culturing hBSCs may be cultured for 4 to 7 days to form spheroids, further culturing for another 2 to 3 weeks, transferring to a mammary differentiation media for an additional 3 to 4 weeks of culture, a total culture time of up to 8 weeks (“[hBSCs] were initially grown as spheroids. By day 4–7, some cells had attached. The remaining spheroids were transferred into new wells where adherent cells appeared in 1–2 days. Both the initial and subsequent attached cells were cultured for another 2–3 weeks, with media changes every 3–5 days. For directed differentiation, primary and first- to third-passage breast-milk cell cultures were incubated in differentiation media at 37 °C and 5% CO2 for 3–4 weeks.” (emphasis added)).
Applicant argues that the claimed culturing steps require culturing in suspension for both culture phases; applicant argues that Hassiotou fails to disclose using suspension for the directed differentiation steps (Response p11-13).
In response, Hassiotou discloses three different approaches for directed differentiation of hBSCs. In the third approach, breastmilk derived spheroids are cultured under 3D conditions (“directed differentiation in 3D conditions was examined by growing breastmilk-derived spheroids in differentiation media for a longer period.”). Hassiotou further discloses that for “spheroid culture breastmilk cells were seeded in ultra-low binding plates”. Therefore, there is a clear suggestion present in Hassiotou that all phases of culturing may be performed in suspension.
Applicant argues that a skilled artisan would not be motivated to use a 3D suspension culture for a longer period of time due to the stresses placed on cells (Response p13-14). Applicant points to additional references in support of this position (Response p14).
As noted above, Hassiotou explicitly discloses that the spheroids are cultured in a mammary differentiation media for 3 to 4 weeks (i.e., a longer time frame). Hassiotou also discloses that the spheroids are cultured in 3D conditions for the directed differentiation. Therefore, applicant’s arguments are not considered persuasive.
Claim(s) 3-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hassiotou in view of Gupta.
Applicant argues that Gupta fails to cure the deficiencies noted in Hassiotou; that Gupta likewise fails to discloses suspension culture (Response p14-15).
In response, Hassiotou explicitly discloses culturing in suspension. Therefore, applicant’s arguments are not considered persuasive.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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