DETAILED ACTION
Introductory Remarks
Applicants are advised that the examiner for this application has changed. All communications should now be directed to Kara Johnson, AU 1632.
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.
Election/Restrictions
Applicant’s election without traverse of group I, claims 1-9 in the reply filed on 7/25/25 is acknowledged.
Claims 1-12 are currently pending.
Claims 10-12 are withdrawn as directed to non-elected inventions.
Claims 1-9 are elected and examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms MAMMOCULT (StemCell Technologies, Vancouver, Canada), EPICULT (StemCell Technologies, Vancouver, Canada), MATRIGEL (MedSkin Solutions, Billerbeck, Germany)
which are trade names or marks 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.
Claim Objections
Claims 2, 4, 7-9 are objected to because of the following informalities. Appropriate correction is required.
Claims 2, 4, 8-9 each contain a Markush group in which an Oxford comma is missing prior to the ultimate member of the Markush group.
Claim 7 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. 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 1-9 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 claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
Generally, when the claims are indefinite, vague or unclear, they cannot be construed without speculation or conjecture; therefore, the indefinite claims are not treated on the merits with respect to prior art. See In re Steele, 305 F.2d 859, 862 (CCPA 1962) (A prior art rejection cannot be sustained if the hypothetical person of ordinary skill in the art would have to make speculative assumptions concerning the meaning of claim language.); see also In re Wilson, 424 F.2d 1382, 1385 (CCPA 1970) ("If no reasonably definite meaning can be ascribed to certain terms in the claim, the subject matter does not become obvious-the claim becomes indefinite."). Notwithstanding Steele, the Office has made every attempt to construe the claims in what the Office believes is the intent of the Applicants in the interest of compact prosecution. The following are exemplary of some of the issues present in the current claims, but may not represent an exhaustive listing of all issues present.
The term “mammary-like” in claim 1 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 1 contains the limitation “generating lactocytes mammary-like gland organoids derived from mammalian adult breast stem cells (mBSCs). It is unclear if this limitation is indicating that the lactocytes or the organoids are derived from mBSCs.
Claim 2 recites in full all the limitations of claim 1, as well depending from claim 1. It is consequently unclear if claim 2 requires two steps of generating lactocytes and secreting milk.
The term “non-standard” in claim 2 is a relative term which renders the claim indefinite. The term “non-standard” 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.
Claim 2 contains the limitation “bioactives from exosome” it is unclear what this limitation is intending to convey.
Claim 3 recites the limitation "the human milk like product". There is insufficient antecedent basis for this limitation in the claim.
Claim 5 contains the limitation, wherein culture conditions according to step A) are adapted to generate lactocytes derived from human breast milk stem cells (HBSCs) capable to secret a non-standard human milk like product”. It is unclear what this limitation is intending to convey.
Claim 6 recites the limitation "under step C)". There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the human milk like product". There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the human milk like product". There is insufficient antecedent basis for this limitation in the claim.
Claim Interpretation
For examination purposes, in view of the above rejections, applicants claims are interpreted as follows:
1. A method for producing a mammalian milk-like product comprising: A) generating organoids containing lactocytes, wherein the organoids are generated from mammalian adult breast milk stem cells (mBSCs); and B) inducing the lactocytes to secrete the mammalian milk-like product”.
2. The method according to claim 1 wherein the mammalian milk-like product is a human milk-like product comprises one or more nutrients or bioactives selected from the group consisting of: proteins, peptides, lipids, carbohydrates, vitamins, minerals, choline, myoinositol, L-carnitine, growth factors, cytokines, probiotics, extracellular vesicles, and secretory IgA
3. The method according to claim 2, further comprising: C) treating the mammalian milk-like product to obtain a modified human milk-like product.
4. The method of claim 3, wherein the treating is selected from the group consisting of: a purification step, an isolation process, an extraction process, a fractionation step, an enrichment process, an enzymatic treatment, the addition of further components, and combinations thereof.
8. The method of claim 1, wherein the mammalian milk-like product further comprises bioactives selected from the group consisting of: oligosaccharides, lipids, and proteins.
9. The method of claim 1, wherein the mammalian milk-like product further comprises bioactives selected from the group consisting of: lactose, C12:0, C16:0, C18:0, C18:1 n-9, C18:2, lactoferrin, and alphalactalbumin.
With respect to claims 5 and 6, the claims cannot be construed without speculation or conjecture. Therefore, claims 5 and 6 are not treated on the merits with respect to prior art. See In re Steele, 305 F.2d 859, 862 (CCPA 1962) (A prior art rejection cannot be sustained if the hypothetical person of ordinary skill in the art would have to make speculative assumptions concerning the meaning of claim language.); see also In re Wilson, 424 F.2d 1382, 1385 (CCPA 1970) ("If no reasonably definite meaning can be ascribed to certain terms in the claim, the subject matter does not become obvious-the claim becomes indefinite.").
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 1-9 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 producing organoids containing lactocytes from other mammalian species. The specification also 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 limit the species of mammal, and so 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; “prolacting supplementation is a pivotal step for inducing lactation-specific functionality”).
The art appears to be silent with respect to establishment of organoids from breastmilk stem cells from any species beyond humans.
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 1-9, 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 1-9 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 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 claim 1, Hassioutou discloses methods of producing mammary-like cells and organoids from a population of hBSCs (Abstract, Introduction; Specification p11 ln 26-p 12 ln 7, “mammary like cells and/or organoids can be generated according to any reported method”, “Hassiotou… represents a protocol to generate human mammary like cells and/or organoids from hBSCs”). Hassioutou discloses culturing hBSCs under conditions such the cells form spheroids, and further differentiating the spheroids into mammary organoids (Cell culture, In vitro differentiation, 3D culture of breastmilk stem cells enriches for self-renewal ESC TFs).
Hassioutou does not explicitly disclose inducing the lactocytes to secrete a mammalian milk-like product. However, Hassioutou discloses that fat globules form under mammary differentiation conditions, suggesting milk production may be possible (Fig. S7). Hassioutou 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 Hassioutou 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, Hassioutou 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, Hassioutou does not disclose further treating the mammalian milk-like product to obtain a modified product. Regarding claim 4 Hassioutou 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 Hassioutou 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 Hassioutou to produce milk according to the methods of Gupta as a use of a known technique to the method of Hassioutou to yield the predictable result of producing a milk.
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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/KARA D JOHNSON/Primary Examiner, Art Unit 1632