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 .
Claim Status
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.
Claims 1 – 10 are rejected under 35 U.S.C. 103 as being unpatentable over Kumamaru et al. (U.S. Patent Application Publication No. 2020/0087623; hereinafter Kumamaru) in view of Guo et al. (Fgf8b-containing spliceforms, but not Fgf8a, are essential for Fgf8 function during development of the midbrain and cerebellum. Dev Biol. 2010 Feb 15;338(2):183-92; hereinafter Guo).
Regarding claims 1 – 7, Kumamaru discloses a method of generating spinal cord neural stem cells (NSC) comprising contacting human (Abstract) pluripotent stem cells (hPSC) in a stem cell-appropriate medium. Kumamaru further discloses in some embodiments that the medium comprises (para. [0042]): SB-431542 at a concentration of 5 – 10 µM, CHIR99021 at a concentration of 3 – 4 µM, FGF2 and FGF8 are used at a concentration of 25 – 100 ng/ml each, 100 nM of LDN193189 (para. [0068]), and no DAPT. Regarding claims 1 and 6, Kumamaru teaches all of the elements of the current invention as stated above except for using FGF-8b in the medium for generating NSCs.
However, Guo discloses that FGF-8a and FGF-8b have distinct activities (Abstract) in the developing midbrain and hindbrain (MHB) due to their different binding affinities with FGF receptors. Guo further discloses/provides motivation by demonstrating that Fgf8b and not Fgf8a deletion leads to the loss of multiple key regulatory genes, including Fgf8 itself, in the MHB region (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kumamaru’s method for generating spinal cord NSCs from hPSCs with the isoform of FGF-8, FGF-8b. Doing so would be expected to lead to a successful outcome, according to Guo due to FGF-8b’s role in gene regulation.
Regarding claim 8, Kumamaru discloses in some embodiments, the hPSC are human embryonic stem cells (para. [0003]).
Regarding claim 9, Kumamaru discloses a 10 day culture period (para. [0041]).
Regarding claim 10, Kumamaru and Guo teach all of the elements of the current invention as stated above except the additional 30 – 60 days of culturing. However, Kumamaru discloses that 20 days after neural induction, the NSCs differentiated into PAX6+/SOX2+ dorsal and NKX6.1+/SOX2+ ventral spinal cord progenitors (para. [0057]), Example 2. Long-Term.., Fig. 9D).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the teaching of Kumamaru on the spinal cord progenitor induction for an additional 10 days, to allow for the NSCs to differentiate into spinal cord progenitors before engrafting the cells into the spine. Doing so would allow for the cells to be functional as spinal cord cells before being engrafting into the spinal cord injury site.
Claims 11 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over Kumamaru and Guo as applied to claims 1 – 10 above, and further in view of Xiaojun et al. (U.S. Patent Application Publication No. 2021/0139858; hereinafter Xiaojun).
Regarding claims 11 – 13 and 19, Kumamaru and Guo teach all of the elements of the current invention as stated above except explicitly disclosing that the spinal cord neural stem cells are karyotypically stable. However, Xiaojun discloses in an invention related to a serum-free hPSC culture medium, a G-bank karyotyping assay for determining karyotypical stability (para. [0021]) in hPSCs. Xiaojun further discloses that karyotypic stability can diminish over time depending on the medium used for culture. Also, karyotypic instability can cause chromosomal abnormalities in the cells, which leads to poor outcomes for neural cell preparations.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching and G-bank karyotyping assay of Xiaojun with the spinal cord NSC generating method of Kumamaru and Guo. Doing so would allow for the generation of a spinal cord neural stem cell as described in instant claim 13. Also, the stem cells of Kumamaru and Guo can be tested for karyotypic stability.
Regarding claims 14 – 16, Kumamaru discloses (para. [0054]) that the cultured NSCs are capable of being used for implantation into a patient for a therapeutic effect (spinal cord injury, [0061], Example 4); (para. [0033], amyotrophic lateral sclerosis (ALS)), as they will survive, engraft, and form functional connections with cells of the recipient.
Regarding claims 17 – 18 and 20, Kumamaru discloses (para. [0012], Figs. 3A – P: Survival, Differentiation…) that spinal cord grafts robustly extend axons for three months in the spinal cord injury site in vivo. Kumamaru further discloses the neuronal and glial differentiation (para. [0022], Fig. 13B, Neuronal Subtypes…) of the NSCs in vivo.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached M-F 7:30A - 5:00P.
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/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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