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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/7/2026 has been entered.
Withdrawn Rejections
The rejection of claims 5-6 and 8, 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn. The amendments to the claims fix the dependency issues of record.
The rejection of claim(s) 1, 3, 5-6, 8, 10, 12-14, and 19, under 35 U.S.C. 103 as being unpatentable over Pedersen et al., 2016 (WO 2016/009196 A1) in view of Khan et al., 2021 WO 2021/247844 A1), Kim, Kwang-Soo, 2020 (WO 2020/237104 A1), Bai et al., 2018 (J. Vis. Exp. (138), e58252, p. 1-6), Secreto et al., 2017 (Stem Cells Translational Medicine, 6: 1829-1839), and Maddah et al, 2014 (Journal of Laboratory Automation 19(5):454-460), is withdrawn. The above combined prior art does not teach the newly added limitations for the differentiation culture.
The rejection of claim(s) 1, 12, 14 and 16, under 35 U.S.C. 103 as being unpatentable over Pedersen et al., 2016 (WO 2016/009196 A1) in view of Khan et al., 2021 WO 2021/247844 A1), Kim, Kwang-Soo, 2020 (WO 2020/237104 A1), Bai et al., 2018 (J. Vis. Exp. (138), e58252, p. 1-6), Secreto et al., 2017 (Stem Cells Translational Medicine, 6: 1829-1839) and Maddah et al 2014 (Journal of Laboratory Automation 19(5):454-460), as applied to claims 1, 3, 5-6, 8, 10, 12-14, and 19 above, and further in view of Matinez Fraiz et al., 2019 (US 20190365951 A1), is withdrawn. The remarks regarding teaching away on page 11 of Applicant’s response is found persuasive.
Claim Objections
Claim1 is objected to because of the following informalities: In general the claims recite superfluous language that cause difficulty in discerning the claimed invention. Steps are written in wherein clauses which causes question as to if they are intended to further limit the claim. Ultimately, the claim language does not rise to the level of indefiniteness because one of ordinary skill can figure out what is being claimed. However, amendments that eliminate some of the superfluous language and removing intended active steps from wherein clauses would be remedial. Appropriate correction is required. See example this paragraph for the types of amendments that would clarify the claims.
Example for claim 1 would be as follows:
A method of manufacturing viable autologous cardiac lineage cells, the method comprising: (i) obtaining a skin biopsy from a subject to obtain a patient specific sample; (ii) producing a plurality of fibroblasts from the patient specific sample; (iii) culturing the plurality of fibroblasts in a pluripotency reprogramming medium to obtain a plurality of induce pluripotent stem cells (iPSCs) that are confluent in culture; (iv) subjecting each of the iPSC of the plurality of iPSC to an etoposide sensitivity test and automated image capturing to determine cell viability; (v) selecting a confluent plurality of iPSC deemed viable by step (iv); (vi) culturing the confluent plurality of iPSC deemed viable under expansion conditions in a monolayer to produce a plurality of expanding cells; (vii) culturing the plurality of expanding iPSC cells in ECM under 3D conditions to produce a 3D culture of expanded iPSCs; (viii) culturing the 3D culture of expanded iPSCs in a first cardiac differentiation medium comprising Activin A, BMP4 and to producing a plurality of differentiating cells; (ix) culturing the plurality of differentiating cells in a second cardiac differentiation medium comprising Activin A, BMP4, and IWP4 to produce a plurality of viable cardiac lineage cells; (x) washing the plurality of cardiac lineage cells with DPBS comprising calcium and magnesium; and (xi) separating and dissociating the plurality of viable cardiac lineage cells to produce a viable single-cell suspension.
Examiner notes that this example above is exemplary for the types of amendments that would clarify the claim. It is not an admission of allowable subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 1, 3, 5-8, 10, 13, and 19 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
When determining if a newly added recitation or amendment to the claims has adequate written description, the breath of the newly added recitation or amendment is determined first. Then, the specification and claims, as originally filed, are examined to determine if sufficient explicit or implicit description for breadth of the newly added recitation.
Claim 1 newly recites, “a first supplemental media comprising CHIR99021 present during an initial phase of differentiation and subsequently adding a second supplementary media comprising IWP4 during a later stage of differentiation”.
The originally filed claims and specification were searched for a literal recitation of the above newly added limitations. However, no such literal recitation was found. As such, the specification and claims as originally filed do not have explicit written support for the recitation.
When reviewing the original disclosure, the following closest disclosure was found (citations from the published application):
[0053] Still referring to FIG. 1, in some cases, supplementary media may include a first inhibitor containing CHIR. As used in this disclosure, an “inhibitor” is a molecule that binds to a specific target, such as an enzyme or a receptor, and reduces or prevents its activity (i.e., signaling pathway) In a non-limiting example, inhibitor may be naturally occurring or synthetic molecules. Inhibitor may be used to modulate cellular processes by selectively blocking or dampening the activity of specific proteins or signaling pathways. “CHIR (CHIR99021),” for the purpose of this closure, is a small molecule inhibitor of glycogen synthase kinase 3 (GSK-3), wherein the GSK-3 is a serine/threonine protein kinase involved in various cellular processes, such as cell signaling, proliferation, differentiation, apoptosis, and the like. CHIR99021 may be used to promote mesoderm formation and cardiomyocyte differentiation. In a non-limiting example, CHIR99021 may act by selectively inhibiting both the alpha and beta isoforms of GSK-3, thereby leading to the activation of the Wnt signaling pathway. CHIR99021 may be added to basal media at day 0 after pre-diff passage.
[0054] Still referring to FIG. 1, in some cases, supplementary media may include a second inhibitor containing IWP 4. As used in this disclosure, an “IWP 4 (inhibitor of Wnt Production-4)” is a small molecule inhibitor that selectively blocks the secretion and activity of Wnt proteins. In a non-limiting example, IWP-4 may inhibit the membrane-bound O-acyltransferase porcupine, an enzyme essential for the maturation and secretion of Wnt ligands, thereby preventing the secretion of Wnt proteins and modulate Wnt signaling pathway. Additionally, or alternatively, inhibitors may be used in combination. In a non-limiting example, IWP-4 may be sued in combination with other growth factors and signaling molecules to direct the differentiation of plurality of iPSCs into cardiac lineage cells; for instance, and without limitation, IWP-4 may be used to inhibit Wnt signaling at specific stages of the differentiation process, working in conjunction with other factor such as, without limitation, activin A, bone morphogenetic protein 4 (BMP4), CHIR99021, and the like to guide iPSCs toward a cardiac lineage. IWP 4 may be added to basal media at day 3 after pre-diff passage.
It is noted that these paragraphs from the specification were cited by Applicant as providing support for the claim amendments. However, the above paragraphs are not commensurate in scope with the newly added recitation. In particular the above describes adding CHIR99021 with basal medium at day 0 after pre-differentiation passage. However, the claims broaden this scope to recite differentiation media “with a first supplementary media comprising CHIR99021 present during an initial stage of differentiation”. Similarly the supplementation of the media with IWF4 in the claims broaden the scope of the above disclosure from the specification, reciting “subsequently adding a second supplementary media comprising IWP4 during a later stage of differentiation”, whereas the original disclosure states “IWP 4 may be added to basal media at day 3 after pre-diff passage”. As such, the newly added recitation impermissibly broadens the scope of the original disclosure. As such, the above citations from the original disclosure fails to provide adequate implicit written description for the newly added recitation.
In conclusion, the newly added recitation, “a first supplemental media comprising CHIR99021 present during an initial phase of differentiation and subsequently adding a second supplementary media comprising IWP4 during a later stage of differentiation”, constitutes new matter because the originally filed disclosure fails to provide explicit or implicit support for the breadth of this newly added recitation. The newly added recitation impermissible broaden the scope of the disclosure to include embodiment that were not originally disclosed and thus the claims comprise new matter.
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 13 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 13 recites, “an optimized serum-free supplement”. The term “optimized” renders the recitation indefinite because it is not apparent for the serum-free supplement is optimized.
Relevant Prior Art
A close prior art is Mendjan (US2025/0321226 A1 pub date:3/19/2021). Mendjan A method of generating a heart organoid comprising the steps of: a) providing pluripotent stem cells; b) inducing mesoderm differentiation in the presence of a WNT activator and/or GSK3-beta inhibitor, and further in the presence of a PI3 kinase inhibitor, in a 3D culture in a low attachment culture, wherein the cells bind to each other instead of a culturing vessel to form aggregates of the cells, thereby producing an aggregate of mesoderm cells; or inducing mesoderm differentiation in the presence of a WNT activator and/or GSK3-beta inhibitor, wherein the WNT activator and/or GSK3-beta inhibitor and/or an optional PI3 kinase inhibitor are in an amount sufficient to differentiate the pluripotent stem cells to exit pluripotency in an amount at least 90% of the pluripotent stem cells within 40 hours of starting induction, thereby producing an aggregate of mesoderm cells, wherein the cells are treated with fibroblast growth factor and/or albumin; and c) differentiating the mesoderm cells of step b) into cardiac cells in a 3D culture in a low attachment culture, wherein the cells aggregate with each other instead of binding to a culturing vessel to form aggregates of the cells, in the presence of cardiac differentiation factors and in the absence of a WNT activator and/or in the presence of a WNT antagonist, for at least 3 days, preferably for 3-7 days, for cardiac mesoderm formation and formation of an inner cavity. However, the method does not teach adding a second supplement media comprising IPW4 so as to have activin, BMP4, and CHIR99021 and IPW4 in the same medium as claimed. Mendjan does not further wash and separate the cardiac lineage cells as claimed.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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