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 .
Status of Claims
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on 21 November, 2025. Claims 1 – 2, 4, 6 – 7, 12, 15 – 19, 21, 24 – 25, and 28 – 32 are currently pending. Claims 1 and 4 have been amended in the Applicant’s amendment filed 21 November, 2025. No claims have been added or canceled in the Applicant’s amendment filed 21 November, 2025.
Applicant's election, without traverse, in the reply filed 20 July, 2025 of Group I, claims 1 – 2, 4, 6- 7, 12, and 15, directed to a method for preparing induced dopaminergic neuronal progenitors (iDPs) is acknowledged.
Claim 16 – 19, 21, 24 – 25, and 28 - 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1 – 2, 4, 6- 7, 12, and 15are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 21 November, 2025 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed 21 March, 2022, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/KR2020/012721, filed 21 September, 2020, which claims the benefit of KR10-2019-0116258, filed 20 September, 2019.
The Examiner acknowledges the untranslated certified copy of the foreign application, filed on 21 March, 2022.
Therefore, the earliest priority date is 20 September, 2019.
Claim objections
Claims 1, 4, and 7 are objected to because of the following informalities: abbreviations such as Oct4, EGG, Wnt1 etc. should be spelled out at the first encounter in the claims. Appropriate correction is required.
Withdrawn Objections/Rejections
Nonstatutory Double Patenting
The rejection of claims 1 – 2, 4, 6 – 7, 12, and 15 is withdrawn on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 - 9 of U.S. Patent No. 10226486 B2 (hereinafter referred to as “Cho”) (published 12 March, 2019), and in view of You et al. (hereinafter referred to as “You”) (US20180155685 A1, published 6 July, 2018).
Claim 1 has been amended and the claims no longer read on Cho and You.
In view of the withdrawn rejection, Applicant’s arguments are moot.
Claim Rejection - 35 USC § 112(b)
The rejection of claims 1 – 2, 4, 6 – 7, 12, and 15 is withdrawn 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 has been amended and is no longer indefinite.
In view of the withdrawn rejection, Applicant’s arguments are moot.
Maintained Objections/Rejections
Claim Rejection - 35 USC § 103
The rejection of claims 1 – 2, 4, 6 – 7, 12, and 15 is maintained under 35 U.S.C. 103 as being unpatentable over Cho et al. (hereinafter referred to as “Cho”) (US20160256495 A1, published 9 August, 2016, issued as U.S. Patent No. 10226486 B2, published 12 March, 2022), and further in view of You et al. (hereinafter referred to as “You”) (US20180155685 A1, published 6 July, 2018).
Regarding claims 1 (in part), 4 (in part), and 7 (in part), Cho teaches a method for preparing induced dopaminergic neuronal progenitors (iDPs) comprising Oct4, Sox2, Klf4, and c-Myc genes in adult cells (Abstract) (interpreted as introducing Oct4 into adult cells, instant claim 1 (in part)). Cho teaches that the OSKM factor-expressing cells (cells expressing Oct4, Sox2, Klf4, and c-Myc genes) were cultured in EGF and FGF2 to induce reprogramming to the dopaminergic neuronal progenitors (Paragraph [0104]). Cho teaches the direct reprogramming of these adult cells to iDPs by treating the cells with SHH and FGF8 (Abstract). Cho teaches that the method for preparing iDPs comprising Wnt signaling agonists including Wnt1 (claim 8) (referring to instant claims 1 (in part), 4 (in part), and 7 (in part)). Cho teaches 0.2 mM ascorbic acid is added to the culture for neuronal cell differentiation (Paragraph [0105]) (referring to instant claim 7 (in part)). Cho teaches that Dopaminergic Neuronal Progenitors (DPs) are a type of neural stem cells (Paragraph [0043]).
Regarding claim 2, Cho teaches that the adult cells are blood cells or fibroblasts (Claim 4). Cho teaches that the patients’ own somatic cells can be used (Abstract).
Regarding claim 12, Cho teaches that OSKM factors were included in the culture medium from D0 to D5 (Paragraph [0102]). Cho teaches that 100 ng/mL FGF8, 2 ng/mL FGF4, and 20 ng/mL FGF were added to medium for the next 8 days (Paragraph [0104]). Cho teaches that Wng signaling was activated at the late stage (Paragraph [0115]).
Regarding claim 15, Cho teaches the direct reprogramming of the adult cells to the iDPS (Abstract).
Cho does not specifically exemplify culturing the cell in a medium comprising TGF-β (instant claim 1 (in part), 4 (in part), and 7 (in part)), that the adult fibroblasts are derived from humans, the properties exhibited by the induced dopaminergic neuronal progenitors (instant claim 1 (in part)), and the method further comprises adding Y-27632 (instant claim 6).
Regarding claims 1 (in part), 4 (in part), claim 6, and claim 7 (in part), You teaches a method of inducing oligodendrocyte precursor cells (OPCs) through direct reprogramming from human somatic cells, wherein the OPCs are useful as a cell therapeutic agent for an intractable demyelinating disease (Abstract). You teaches direct reprogramming through human somatic cells into which a nucleic acid encoding an Oct4 protein has been introduced (Paragraph [0001]). You teaches the cell were proliferated by FGF2 (Paragraph [0092]). You teaches that the method of inducing OPCs from human somatic cells through direct reprogramming includes culturing human somatic cells, into which a nucleic acid encoding an Oct4 protein is introduced, in a medium containing a TGF-β inhibitor, a ROCK inhibitor, a histone deacetylase inhibitor, and SHH (Paragraph [0012]) (interpreted as the adult cells are derived from humans (instant claim 1 (in part)). Specifically, You teaches that A83-01 is a transforming growth factor-β type I (TGF-β type I) receptor inhibitor, which is a substance that binds to a TGF-β type I receptor to interfere with a normal signaling process of TGF-β type I (Paragraph [0044]) (referring to instant claims 1 (in part), 4 (in part), and 7 (in part)). You teaches that TGF-β inhibits the proliferation of neural stem cells, and the proliferation of neural stem cells is promoted by treatment with the inhibitor (Paragraph [0044]). You teaches that Y-27632 can block ROCK signal inducing apoptosis of neural cells and neural stem cells and a PTEN signal inhibiting proliferation of the neural stem cells, and is expected to inhibit the apoptosis of the neural stem cells and increase a self-renewal activity and a self-proliferation activity (Paragraph [0045]) (referring to instant claim 6).
Therefore, in view of the benefits of inducing oligodendrocyte precursor cells (OPCs) through direct reprogramming from human somatic cells, wherein the OPCs are useful as a cell therapeutic agent for an intractable demyelinating disease as taught by You, it would have been prima facia obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to supplement the reagents used in the method for preparing induced dopaminergic neuronal progenitors (iDPs) as taught by Cho, with the addition of A83-01, a TGF-β type I receptor inhibitor, and Y-27632, a ROCK inhibitor, as taught by You, with the reasonable expectation of success in increasing the proliferation activity and self-renewal activity of the neuronal progenitor cells. It would have been prima facia obvious to combine the cited sources because Cho teaches a method wherein OSKM factor-expressing cells (cells expressing Oct4, Sox2, Klf4, and c-Myc genes) were cultured in EGF and FGF2 to induce reprogramming to the dopaminergic neuronal progenitors, wherein dopaminergic neuronal progenitors are a type of neural stem cells, and You teaches the direct reprogramming through human somatic cells into which a nucleic acid encoding an Oct4 protein has been introduced, wherein A83-01 and Y-27632 are introduced to inhibit apoptosis, and increase the self-renewal activity and self-proliferation activity of the neural stem cells.
Although the combined references do not specifically exemplify the properties exhibited by the induced dopaminergic neuronal progenitors (instant claim 1), Cho and You teach the instantly recited method of preparing induced dopaminergic progenitors (iDPs), such that by performing the method, the progenitors generated will inherently have the properties as stated in claim 1 (See; MPEP 2112.1, 2112.01(II) and MPEP 2112(V)).
Response to Arguments as they apply to rejection of claims 1 – 2, 4, 6 – 7, 12, and 15 under 35 USC § 103
Applicant’s arguments filed 21 November, 2025 have been fully considered but they are not persuasive. Applicant essentially asserts (a) claim 1 of the present application pertains to human iDPs(hiDPs), where as Cho relates to mouse DPs (miDPs) (pg. 11, first and second paragraph); (b) Example 9 of the specification shows that the reprogramming conditions of mouse IDPs have no effect on the direct reprogramming of the human fibroblasts into hiDPs (pg. 11, third paragraph), (c) contrary to Yuan and You, iNSC is not produced in the Step b) of the method of claim 1 (pg. 11, sixth paragraph); (d) the Office has not shown the Cho and You teach any heterogenous expression characteristics (pg. 11, last paragraph, and pg. 12 first and second paragraph).
Regarding (a) and (b), Applicant’s argument that Cho relates to mouse DPs is not persuasive. Please note that the rejection above has been amended to show that the adult cells have been derived from humans.
As an initial matter, Applicant is reminded that none of the references has to teach each and every claim limitation. If they did, this would have been anticipation and not an obviousness-type rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s assertion that Cho does not teach hiDPs is not found persuasive. Applicant is reminded that the rejection of record is based on the combination of Cho and Yuan, wherein Cho clearly teaches the a method wherein OSKM factor-expressing cells (cells expressing Oct4, Sox2, Klf4, and c-Myc genes) were cultured in EGF and FGF2 to induce reprogramming to the mouse dopaminergic neuronal progenitors, wherein dopaminergic neuronal progenitors are a type of neural stem cells, and You teaches the direct reprogramming through human somatic cells into which a nucleic acid encoding an Oct4 protein has been introduced, wherein A83-01 and Y-27632 are introduced to inhibit apoptosis, and increase the self-renewal activity and self-proliferation activity of the neural stem cells. Thus, Cho and Yuan teach all the limitations of the instant claims.
The Applicant notes Example 9 of the specification shows that the reprogramming conditions of mouse IDPs have no effect on the direct reprogramming of the human fibroblasts into hiDPs. The as-filed Specification teaches that The present inventors have examined whether the conditions previously used for directly reprogramming of mouse fibroblasts into iDPs could be used in human fibroblasts so as to produce human induced dopaminergic neuron precursors (hiDPs) (Paragraph [0343]). This is referring to the conditions as taught by Cho, such that those conditions taught by Cho do not yield hiDPs. The conditions taught by Cho does not require the use of TGF-β and Y-27632. As the rejection is based on the combination of Cho and You, wherein when one of ordinary skill in the art will be able to combine these teachings to yield iDPs.
Regarding (c), Applicants argue that You describes that iNSCs were produced by reprogramming, followed by differentiation to yield DPs, and that iNSCs are not produced by the method of claim 1. Applicant’s argument is not found persuasive. Specifically, Cho teaches the use of OSKM factor-expressing cells (cells expressing Oct4, Sox2, Klf4, and c-Myc genes), and that You teaches reprogramming on cells that encode Oct4 and wherein A83-01 and Y-27632 have been introduced. Thus, one of ordinary skill in the art would not care or expect whether the iNSCs are produced, rather that the addition of A83-01 and Y-27632 on cells expressing Oct4 will ultimately lead to the production of DPs and increase the self-renewal activity and self-proliferation activity of the neural stem cells.
Applicant is reminded that
MPEP 2144(I) teaches:
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); Ex parte Clapp, 227 USPQ 972 (Bd. Pat. App. & Inter. 1985) (examiner must present convincing line of reasoning supporting rejection); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning) (underline added).
Thus, one of ordinary skill in the art would reference You to increase the self-renewal activity and self-proliferation activity of the neural stem cells to ultimately yield DPs.
Regarding (d), Applicant notes that the prior art does not teach any heterogenous expression characteristics. As an initial matter, the instant claims are directed to a method. Thus, by following the method, the cells would inherently have the heterogeneous expression characteristics described in the amended claim 1.
MPEP § 2112(I) states:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that, "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP § 2112.01 with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103.
MPEP § 2112(II) indicates:
there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999) ("If a product that is offered for sale inherently possesses each of the limitations of the claims, then the invention is on sale, whether or not the parties to the transaction recognize that the product possesses the claimed characteristics."); Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1348-49, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999) ("Because ‘sufficient aeration’ was inherent in the prior art, it is irrelevant that the prior art did not recognize the key aspect of [the] invention.... An inherent structure, composition, or function is not necessarily known."); SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1343-44, 74 USPQ2d 1398, 1406-07 (Fed. Cir. 2005).
Furthermore, as noted in MPEP § 2112.01(I), where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). As shown above, Cho and You teach the instant claims, and thus, the resulting cells would have the properties as described by claim 1.
Conclusion
Claims 1 – 2, 4, 6 – 7, 12, and 15 remain rejected.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of
the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638