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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 August 7, 2025 has been entered.
Status of Application, Amendments and/or Claims
Claim listing filed on August 7, 2025 is pending. Claims 8-13, 18-19, and 21 are canceled. Claims 16 and 22-23 are amended. Claims 1-7 and 14-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species in the election made without traverse in the reply filed on July 3, 2024. Claims 16-17, 20, and 22-24 are examined upon their merits.
Withdrawn Claim Rejections
The rejection of Claims 20 and 24 under 35 U.S.C. 103 as being unpatentable over Mica et al. Cell Rep. 2013 in view of Stebbins University of Wisconsin-Madison 2017 is withdrawn in view of Applicant’s declaration under 37 C.F.R. § 1.130(a) submitted on August 7, 2025. The declaration states that the thesis was under a temporary embargo at the University of Madison Library and was not available to the public until July 28, 2018, and the oral defense on May 18, 2017 did not provide details of the claimed protocol. Therefore, Examiner agrees that Stebbins is not prior art to the present application, and the rejection is withdrawn.
Claim Rejections - 35 USC § 112 (New)
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.
Claims 16-17, 20, and 23-24 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 16 recites culturing hPSC in culture medium for “about 15 days” and Claim 20 recites culturing the cells of step (b) for “about 11 days.” Both of these claims describe the length of culture time with the indefinite word “about.” Do the claims encompass ± 2 days, ± 5 days, ± 10 days? Because there is no definition of the term “about” in the specification, the metes and bounds of Claims 16 and 20 cannot be readily determined (MPEP § 2173.05(b)III.A), and Claims 17 and 23-24 are rejected for their dependence on indefinite claims.
Claims 20 and 24 encompass a trademarked culture medium, Essential 6TM Medium, as an essential claimed element. Applicant should note that a trademark or tradename does not denote a particular and fixed element. For example, the tradename “Coca-Cola” has been used on different formulations over the years. MPEP 2173.05(u) states: “If the 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 the 35 U.S.C. 112(b). 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 describe any particular material or product. In fact, the value of a trademark would be lost to the extent that it became the generic name of a product, rather than used as an identification of a source or origin of a product. Thus, the use of a trademark or trade name in a claim to describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name.” Claims 20 and 24 are rejected for indefiniteness by claiming a trademarked product. For the purpose of compact prosecution, E6 media in Claims 20 and 24 will be interpreted as any culture media known in the art prior to the time of filing.
Claim Rejections - 35 USC § 101 (Maintained)
The rejection of Claim 22 under 35 U.S.C. 101 is maintained because the claimed invention is directed to a nature-based product without significantly more. The claim recites a population of p75-NGFR+HNK+ NCSCs which are no different than naturally occurring NCSCs that have the same markers as evidenced by Jiang et al. Stem Cells Dev. 2009 (page 1064 paragraph 1; of record).
Applicant's arguments filed August 7, 2025 have been fully considered but they are not persuasive. Applicant argues that amended Claim 22 is directed to an in vitro population of p75-NGFR+HNK+ NCSCs at a level of purity that is not found in nature. Applicant further argues that the cells are significantly different than the naturally occurring cells due to the ability to study and assess their functionality in a way not possible with the natural occurring cells. These arguments are not persuasive because isolating naturally occurring NCSCs to study their functionality in vitro is not a markedly different characteristic that distinguishes the isolated NCSCs from naturally occurring NCSCs.
MPEP § 2106.04(c).II.C.2 states that in Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75, the patentee discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. The claimed genes had the same genetic structure and nucleotide sequence as the BRCA genes in nature. The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977 ("Myriad's patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes … But isolation is necessary to conduct genetic testing") and 569 U.S. at 593, 106 USPQ2d at 1980 (describing how would-be infringers could not avoid the scope of Myriad’s claims). The case law applies to instant Claim 22 because it is directed to isolated NCSCs that are structurally unchanged from what exists in nature, and if the claim were valid, would improperly give the exclusive right to isolate NCSCs wherein isolation of NCSCs is necessary to conduct basic research. Based on the case law, Claim 22 is directed to a nature-based product without significantly more and the rejection is maintained.
Claim Rejections - 35 USC § 102 (New, necessitated by amendment)
Claims 16 and 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mica et al., Cell Rep. (2013), 3(4):1140-52 (of record). Note, the previous 102(a)(1) rejection in view of Mica is maintained with additional sections of art cited to address the amendments and Claims 22 and 24.
Mica teaches a method of deriving NCSCs from hPSCs by culturing the NCSCs in media for 11 days wherein the media contains a BMP signaling inhibitor; SB431542 which is an ALK5 antagonist to inhibit TGF-β, Activin, and Nodal signaling; and CHIR99021 which inhibits GSK3β to promote WNT signaling (Results, first paragraph and Experimental Procedures, first paragraph). Incubating CHIR99021 in the media from Days 2-11 resulted in ~60% SOX10::GFP+, a measure of NCSCs (Fig. 2C).
Mica further discloses “the axial levels of NC …can be readily patterned using caudalizing FGF2 and RA cues” (pg. 1150, first full paragraph and Figure S1). FGF2 can be incubated in the media from Days 2-11 (Fig. S2B-C). Both CHIR99021 (a GSK3β inhibitor) and FGF2 are taught to be present in the media from Days 2-11, resulting in a 9-Day incubation with both agents which reads on “about 15 days” in Claim 16 (broadest reasonable interpretation applied to “about” since no definition is provided in the specification – see above 112(b) rejection). Note, producing a population of at least 85% p75-NGFR+HNK+ NCSCs is interpreted as an inherent result of performing the claimed method steps, specifically culturing hPSC in culture medium for about 15 days wherein the culture medium comprises FGF2 and a GSK3β inhibitor which are present for the full culture time (MPEP § 2112.01-.02). Because Mica anticipates the claimed method step of 16(a), Mica inherently anticipates the resulting product.
Lastly, Mica uses fluorescence-activated cell sorting to confirm that, on day 11, cells co-expressed Sox10::GFP and c-kit, which it defines as a marker for the melanocyte-competent NC cells (pg. 1143, last paragraph). Figure S1F-G teaches that cell sorting produced a population of NCSCs that are about 90% p75-NGFR+ and HNK+. The exact enrichment level of 90% is a result of experimental optimization such as optimizing gating thresholds (MPEP § 2144.05).
Applicant's arguments filed August 7, 2025 have been fully considered but they are not persuasive. Applicant argues that not only does Mica not teach a culture media comprising FGF2 and a GSK3β inhibitor which are present for the full culture time, Mica teaches that the inclusion of CHIR99021 prior to day 2 or FGF2 prior to Day 8 is detrimental. These arguments are not persuasive because they rely on the claim limitations of “present for the full culture time” wherein the full culture time is defined as “about 15 days” to distinguish the instant method from the method of Mica, but “about 15 days” is not specifically defined in the specification and must be interpreted with the broadest reasonable interpretation (MPEP § 2111). With the appropriate broadest reasonable interpretation, incubating FGF2 and CHIR99021 for 9 days (Days 2-11) as taught in Mica reads on “about 15 days” of the instant claims. Producing a population of at least 85% p75-NGFR+HNK+ NCSCs is interpreted as an inherent result of performing the claimed method steps of Claim 16(a). Therefore, Applicant’s arguments are not persuasive and the rejections are maintained.
Examiner recommends amending the claims to more specifically define the limitation of culturing the hPSC for 15 days to distinguish the instant method from the method of Mica to potentially overcome the 102(a)(1) rejection of record.
Claim Rejections - 35 USC § 103 (Maintained)
The rejection of Claim 17 under 35 U.S.C. 103 as being unpatentable over Mica et al., Cell Rep. (2013), 3(4):1140-52 (of record) as applied to Claims 16 and 22-24 above, and further in view of Vroemen et al., J. Neurosci. Methods (2003), 124(2): 135-143 (of record) is maintained.
Applicant's arguments filed August 7, 2025 have been fully considered but they are not persuasive. Applicant argues that Vroemen fails to cure the deficiencies of Mica which have been addressed in the 102(a)(1) rejection above. The rejection of record is maintained.
Claim Rejections - 35 USC § 103 (New)
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Mica et al., Cell Rep. (2013), 3(4):1140-52 (of record) as applied to Claims 16 and 22-24 above, and further in view of Griffin et al. SSRN June 2018.
The teachings of Mica as they apply to claims 16 and 22-24 are outlined in the rejection above. Mica fails to teach a method further comprising culturing the NCSCs in E6 media with serum for about 11 days to produce a population of brain pericyte-like cells that express NG2 and PDGFRB but not ACTA2 (Claim 20). Note, because E6 media is a trademarked name, the claim is interpreted to encompass any media (see 112(b) rejection above).
Griffin teaches a method of deriving cranial pericytes (cPC) from human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) via neutral crest cells (NCC) (bottom of page 8). The NCC generated from pluripotent stem cells were incubated in non-DMEM base medium with low serum for 14 days to induce and maintain the pericyte fate from NCC (page 9 and Fig. S2). Note, “FBS” in Fig. S2 stands for fetal bovine serum. The resulting cPC express NG2 and PDGFRB but not ACTA2 (Fig. 2B).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of producing NCSCs in Mica to include further culturing the NCSCs in media with serum for about 11 days to produce pericytes as outlined in Griffin. Mica and Griffin both teach a method of producing NCSCs from pluripotent stem cells. Griffin continues the procedure one step further to derive pericytes from the NCSCs. It would have been obvious to one of ordinary skill to combine the prior art elements according to the known methods to yield pericytes from the NCSCs. The motivation to culture NCSCs to produce cranial pericytes is to study their role in disease pathogenesis (Griffin page 3).
Double Patenting (Maintained)
Claims 16 and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 10 and 11 of copending Application No. 17/933,730. Note, the previous provisional double patenting rejection applied to Claim 16 but now applies to Claims 16 and 22-24 due to amendments in both the instant and copending applications.
Applicant's arguments filed August 7, 2025 have been fully considered but they are not persuasive. Applicant requests reconsideration of the double patenting rejection in view of the claim amendments. Examiner maintains that copending 17/933,730 teaches a method of obtaining p75-NGFR+HNK-1+ NCSCs from hPSCs by culturing hPSCs in E6-CSFD medium for about 15 days and sorting the resulting cells to produce an enriched population of p75-NGFR+ NCSCs (Claims 10-11). Copending Claims 10-11 are not patentably distinct from instant Claims 16 and 22-24, and the rejection is maintained.
Conclusion
No claim is allowed.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675