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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/11/2025 has been entered.
Status of the Claims
Claims 1, 4, 8-11, 13-17, and 20-23 are currently pending.
Claims 1, 8-10, and 22 are amended.
Claims 11, 13-17, and 20-21 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 2-3, 5-7, 12, and 18-19 are cancelled.
Claim 23 is newly added.
Claims 1, 4, 8-10, and 22-23 have been considered on the merits.
Withdrawn Rejections
The 112(b) rejections made onto claims 1, 4, 8-10, and 22 are withdrawn in light of the amendments submitted on 11/11/2025.
Maintained Rejections Necessitated by Amendment
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, 8-10, and 22-23 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.
Claim 1 recites a limitation of “a method for reinforcing pluripotency in stem cells”, which is indefinite. The term “reinforcing pluripotency is not a recognized term of art and the specification does not appear to employ or define the terms “reinforce” or “reinforcing pluripotency”. However, the generic dictionary definition of the term reinforce is to support or increase. Therefore, the claim limitation is interpreted to mean a method for strengthening or increasing pluripotency, however it is unclear how one might determine that pluripotency is strengthened or increased. It is further unclear due to the various starting cell types recited in the claim. For example, if the stem cells employed are embryonic stem cells, which are already pluripotent, would maintenance of the pluripotent embryonic stem cell state meet the claimed “reinforcing pluripotency”. In an alternative, if the stem cells employed are adult stem cells, which are multipotent, must the cells be reprogrammed into a fully pluripotent state to meet the claimed “reinforcing pluripotency”. For the sake of compact prosecution, any maintenance of pluripotent stem cell state and/or any increase in pluripotency in multipotent cells is being interpreted to meet the claim limitation of “reinforcing pluripotency”. Appropriate clarification is required.
Claims 4, 8-10, and 22-23 are included in the rejection for being dependent from claim 1.
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.
Claims 1, 4, 9, and 22-23 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Cerullo et al (WO2017037108A1)(reference of record).
Regarding claim 1, Cerullo teaches culturing cells on a nichoid-type substrate (pg. 12, lines 37-38). The cells are taught to be any stem cells, specifically including embryonic and mesenchymal (adult stem cell) as required by claims 1 and 4 (pg. 8, para 4-5). Additionally, Cerullo teaches that the mesenchymal stem cells are able to be isolated from either adipose tissue, bone marrow, placental tissue (i.e. placental stem cells), or umbilical cord (i.e. cordonal stem cells) tissue as required by claim 23 (pg. 15, para 10-11).
Cerullo teaches that the cells are plated on the nichoid substrate and allowed to grow for a certain time, the time is taught to be 10 days as required by claim 1 (pg. 22 para 2 and 7; and pg. 23, para 3). Cerullo also teaches that the most important result was seen on culture day 7 showing that the nichoid 3D structure is necessary and sufficient to maintain pluripotency as required by claim 22 (pg. 25, para 2). Cerullo teaches the growth of embryonic stem cells on the nichoid substrate in Example 2, wherein the embryonic stem cells are tested for their stemness through OCT4 expression (pg. 20, Example 2, and pg. 24 last 4 para spanning para 3 of pg. 25) Cerullo teaches that “in fact, the niche was observed to promote higher levels of expression of OCT4 than both the other two control structures under study. This confirms that the nichoid's 3D structure is necessary and sufficient (given that no chemical conditioning was provided) to maintain pluripotency” (pg. 25, para 2). Based on the claim interpretation described in the 112b rejection above, Cerullo meets the limitations of “reinforcing pluripotency” in claim 1 through “maintaining” the pluripotent state in embryonic stem cells as described by Cerullo.
Cerullo teaches that the cells are detached from the nichoid-type substrate as required by claim 1 and further cultured in suspension as required by claim 9 (pg. 17, para 3-5).
Additionally, Cerullo teaches that using the nichoid substrate, also called a supermatrix by Curello, “permits potency maintenance without continuously inserting chemical factors that condition the cells in the culture medium” and that the “use of the supermatrix according to the invention, both multipotency and pluripotency are able to be maintained even after many divisions of the first stem cell seeded” (pg. 8, para 4).
Therefore, Cerullo anticipates the claims.
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.
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.
Claims 1 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Cerullo et al (WO2017037108A1), as applied to claims 1, 4, 9, and 22-23 above, and further in view of Nie et al (PLOS, 2014) (all of which are references of record).
Regarding claim 8, the limitations of the independent claim are taught above. Cerullo does teach that the cells are detached from the substrate using a trypsin-EDTA solution (pg. 17, para 3). Cerullo does not teach that the cells are detached from the substrate using a sodium citrate solution.
However, Nie teaches about the passaging of adherent human pluripotent stem cells. Nie teaches that sodium citrate gently and efficiently detaches adherent cultures of hPSCs as small multicellular aggregates with minimal manual intervention as required by claim 8 (abstract). Further, Nie teaches that cells which are passaged 25 times using sodium citrate continued to exhibit hPSC morphology (i.e., they remained pluripotent).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the culture method taught by Cerullo with the detachment method employing sodium citrate as taught by Nie to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Nie teaches that sodium citrate gently and efficiently detaches adherent cultures of hPSCs as small multicellular aggregates with minimal manual intervention (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Cerullo with Nie because Nie teaches that cells which are passaged 25 times using sodium citrate continued to exhibit hPSC morphology (i.e., they remained pluripotent).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Cerullo et al (WO2017037108A1), as applied to claims 1, 4, 9, and 22-23 above, and further in view of Carelli et al (Neuropharmacology, 2017) (all of which are references of record).
Regarding claim 10, the limitations of the independent claim are taught above. Cerullo does teach that the nichoid structures have enormous potential in regeneration of neural tissue (pg. 4, para 3). Cerullo does not teach that the cells are erythropoietin (EPO) releasing neural precursor cells as required by claim 10.
However, Carelli teaches about EPO-releasing neural progenitors and the powerful neuroprotective action of EPO both in vivo and in vitro as required by claim 10 (abstract).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the culture method taught by Cerullo with the EPO-releasing neural progenitors taught by Carelli to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Cerullo does teach that the nichoid structures have enormous potential in regeneration of neural tissue (pg. 4, para 3). One of ordinary skill in the art would have a reasonable expectation of success when combining Cerullo with Carelli because Carelli teaches about EPO-releasing neural progenitors and the powerful neuroprotective action of EPO both in vivo and in vitro (abstract).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11/11/2025 have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 7-8), that the results of practicing the method result in an increase of expression of Nanog, SOX2, and Oct4 genes, adult stem cells proliferated on the nichoid “have surprisingly shown to originate a population of viable cells”, once the cells of the invention are transplanted in vivo, they are shown to “not originate tumors”.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that the results of practicing the method result in an increase of expression of Nanog, SOX2, and Oct4 genes, adult stem cells proliferated on the nichoid “have surprisingly shown to originate a population of viable cells”, once the cells of the invention are transplanted in vivo, they are shown to “not originate tumors”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Additionally, Cerullo anticipates the steps of the claimed method. Cerullo teaches the growth of embryonic stem cells on the nichoid substrate in Example 2, wherein the embryonic stem cells are tested for their stemness through OCT4 expression (pg. 20, Example 2, and pg. 24 last 4 para spanning para 3 of pg. 25) Cerullo teaches that “in fact, the niche was observed to promote higher levels of expression of OCT4 than both the other two control structures under study. This confirms that the nichoid's 3D structure is necessary and sufficient (given that no chemical conditioning was provided) to maintain pluripotency” (pg. 25, para 2). Thus, the results of the instant invention must be inherent to the method as taught by Cerullo and a necessary effect of practicing the method. Therefore, the arguments are not found persuasive.
Applicant argues (Remarks, pg. 8, para 4-5) that “these experiments reported in Cerullo include the expansion of such cells on the nichoid substrate for the entire experimental time and the maintenance of the differentiation. In other words, the experiments are performed on differentiated cells, which, in the course of the test, maintain their differentiated status” and that the present application results show an increase in the expression of genes which characterize pluripotency.
In response to Applicant’s argument, Cerullo does in fact teach the culturing of embryonic stem cells on the nichoid substrates which are not differentiated. Cerullo teaches the growth of embryonic stem cells on the nichoid substrate in Example 2, wherein the embryonic stem cells are tested for their stemness through OCT4 expression (pg. 20, Example 2, and pg. 24 last 4 para spanning para 3 of pg. 25) Cerullo teaches that “in fact, the niche was observed to promote higher levels of expression of OCT4 than both the other two control structures under study. This confirms that the nichoid's 3D structure is necessary and sufficient (given that no chemical conditioning was provided) to maintain pluripotency” (pg. 25, para 2). Even though Cerullo does not explicitly recite the claim term “reinforcing pluripotency”, it is clear that the result of Cerullo appears to be identical to that of the instant invention. Thus, the results of the instant invention must be inherent to the method as taught by Cerullo and a necessary effect of practicing the method. Therefore, the arguments are not found persuasive.
Applicant argues (Remarks, pg. 9-10) that the 103 rejections in further view of either Nie or Carelli do not remedy the alleged deficiencies of Cerullo.
In response to Applicant’s argument, the arguments against Cerullo have not been found persuasive for the reasons listed at points 20 and 21 and therefore the argument is not found persuasive.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632