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 .
Claim status
In the reply filed 02 September 2025 applicant has Applicant has amended claims 1, 5, 7, 8, 11 and 12, added new claim 15 and withdrawn claims 13-14. Therefore, claims 1-15 are herein pending.
Election/Restrictions
Applicant previously elected without traverse of Group 1, claims 1-12 drawn to a method of inducing a non-pluripotent mammalian cell into an induced pluripotent stem cell in the reply filed on 07 April 2025. The scope of new claim 15 reads on group 1.
While Applicant elected Group 1 without traverse, applicant argues that Lee and Gnanasambandam do not render obvious the claimed method for these reasons, elected claims 1-12 are inventive over Lee and Gnanasambandam. The argument is moot as the aforementioned combination of references has not been applied in the rejection set forth below.
Claims 13-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 1-12 and 15 are herein under examination.
Priority
This application was filed 05/10/2022 and is a 371 application of PCT/US2020/060071 filed on 11/11/2020, which claims benefit to the Provisional Application 62933926 filed on 11/11/2019. Thus, the earliest possible priority for the instant application is 11/11/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/14/2023, and 09/23/2025 are in compliance with the provisions of 37 CFR 1.97. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure because the copies of references cited by applicant in accordance with MPEP 609, 707.05(b) and 708.02 are not furnished to applicant with the Office action.
Accordingly, the information disclosure statement is being considered all references except, where lined through by the examiner (IDS filed on 07/14/2023). This objection specifically refers to the Non-Patent Literature document titled "Cholesterol-rich lipid rafts are required for release of infectious human respiratory syncytial virus particles”.
Maintained Abstract Objection
The amended abstract of the disclosure filed 02 September 2025 is objected because the amended abstract is only 42 words in length. Therefore, amended abstract is considered non-compliant and maintain the objection.
Applicant is reminded of the proper language and format for an abstract of the disclosure. MPEP §608.01(b) states that the abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Therefore, appropriate correction is required.
Withdrawn Rejections
The prior rejection of claims 1-8 and 11-12 pursuant to 35 U.S.C. 103 as obvious over Lee et al. (US20190161738A1; "Lee") in view of Yu et al. (Journal of Biomolecular Screening, 06 June 2014, Vol. 19, lss. 8, Pgs. 1164-1173; "Yu"), Sachs et al. (US20060014691Al; "Sachs") and Chang et al. (Virology, 422 (2012) 205-213; "Chang") is withdrawn. Applicant argues that Lee emphasizes that mechanical agitation -which induces cell aggregation-is essential for the reprogramming to occur. POSITA would understand that inhibiting mechanosensitive and stretch-activated ion channel would serve the opposite role of applying mechanical agitation, and applying both would be incompatible. Lee's method specifically relies on mechanical agitation of the non-pluripotent cells and aggregation of them for successful reprogram. Further, the claimed method has surprisingly superior efficacy compared to the methods of Lee. For example, the claimed method yields stem cell-like phenotypes overnight (see, e.g., Results in Example in the Specification) whereas Lee's method takes four days (see, e.g., Example 3 of Lee). Therefore, Applicant’s arguments have been fully considered and withdrawn the obviousness rejection.
Therefore, prior rejection on dependent claims 1 and 9-10 under 35 U.S.C. 103 as being unpatentable over Lee et al. in view of Yu et al and Sachs et al. as applied to claim 1 above, and further in view of Gerardo et al. (Sci Rep 9, 9086 (2019); cited in IDS filed 07/14/2023; hereinafter “Gerardo”) is withdrawn.
Claim Interpretation
As per MPEP § 2111 and § 2111.01, “[d]uring patent examination, the pending claims must be ‘given their broadest reasonable interpretation consistent with the specification’" and the words of a claim must be given their ‘plain meaning’ unless such meaning is inconsistent with the specification, wherein ‘plain meaning’ of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. Because applicant has the opportunity to amend the claims during prosecution, giving a claim its broadest reasonable interpretation will reduce the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Yamamoto, 740 F.2d 1569, 1571 (Fed. Cir. 1984).
Below are notes made by the examiner regarding claim interpretation of the most recent set of claims. Applicant is respectfully invited to comment on or dispute any of these statements.
In the present case, the preamble of the claim recites a method for inducing non-pluripotent mammalian cells into pluripotent stem cells using specific conditions. As per MPEP 2111, whether the preamble gives patentable weight or otherwise limits the claim as a whole is to be determined on a case-by-case basis. In the present application, the examiner is interpreting the claim to be limited to methods wherein such a transition from non-pluripotent mammalian cells to pluripotent stem cells does occur.
Claim Rejections - 35 USC § 112(a)
(Written description)
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- 4, 6-7, 9-12 and 15 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 contains subject matter that 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 pre-AIA the inventor, at the time the application was filed, had possession of the claimed invention.
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Claim 1 preamble encompasses a genus of any non-pluripotent mammalian cell (hereinafter “nPMC”);
Claim 1a encompasses any mechanosensitive and stretch-activated ion channel (hereinafter “MSAIC”) inhibitors in any amount sufficient to the ion channel of any nPMC; and,
Claim 1b encompasses any cholesterol reducing agents (hereinafter “CRA”) in any amount sufficient to reduce the cholesterol level of any nPMC;
Claim 1c encompasses any soft extracellular matrix (hereinafter “sECM”) having a Young's elastic modulus of 20 kPa or less.
The specification discloses that the nPMC can be induced according to the disclosed methods wherein, mammalian cells are selected from human fibroblasts and human peripheral blood mononuclear cells. In an embodiment, nPMC are cells that are not genetically modified to express pluripotency inducing factors, such as Oct4, Nanog and Sox2 (See SPEC [0073-0074], [0092], [0095] ¶ of US20220389389A1). Furthermore, SPEC discloses the methods, in which the MSAIC inhibitors (i.e., GsMTX4) were attenuated with multiple methods combined (FIG. 29). For example, embryonic fibroblasts are treated with CRA (i.e., cyclodextrin, e.g., methyl-beta-cyclodextrin (MβCD)), then cultured on the soft hydrogels (i.e., sECM) made of polyacrylamide. In another example, embryonic fibroblasts are treated with GsMTX4, then cultured on the sECM are hydrogels made of polyacrylamide. In an embodiment, the combined use of the cell-cholesterol depletion compound and soft extra-cellular matrix induces more frequent reprogramming and the increased appearance of cells possessing novel differentiated phenotypes ([0092] ¶). Specification also discloses that cells are contacted with the MSAIC inhibitor (GsMTX4) at a concentration of at least 1μM, between about 10μM and in a preferred embodiment, cells are contacted with GsMTX4 at a concentration of 5μM ([0077] ¶ of SPEC) and with the CRA agent (MβCD) at a concentration of at least 1mM, between about 10mM and in a preferred embodiment, cells are contacted with MβCD at a concentration of 5mM ([0083] ¶ of SPEC). Therefore, the specification doesn't provide adequate support in the disclosure for the any MSAIC inhibitors in any amount sufficient to the ion channel of any nPMC; or any CRA in any amount sufficient to reduce the cholesterol level of any nPMC; or any sECM having a Young's elastic modulus of 20 kPa or less that exercise in this invention to inducing any non-pluripotent mammalian cell into pluripotent stem cell.
In the prior art Yu et al. (Journal of Biomolecular Screening, 06 June 2014, Vol. 19, lss. 8, Pgs. 1164-1173; cited in IDS filed 07/14/2023; hereinafter “Yu”) teaches a method to produce an induced pluripotent stem cell (e.g., NPC1 iPSCs) from non-pluripotent mammalian (i.e., patient dermal fibroblasts; cited as a non-pluripotent mammalian cell in the instant specification p. 11 [0034] 26 ¶136 of Yu) and the differentiation of NPC1 iPSCs to NSCs and subsequently neurons for evaluation of drug efficacy (abstract and p. 1165 left-hand column, 2nd ¶ of Yu). Further, Yu discloses that the cell cholesterol reducing agents (i.e., methyl-β-cyclodextrin (MβCD)) in an amount (e.g., 300µM) sufficient to reduce the mammalian cell cholesterol level (Fig. 4C and p. 1168, right-hand column, 2nd ¶ of Yu). Furthermore, Sachs et al. (US20060014691A1; Pub. Date: Jan. 19, 2006; cited in PTO892; hereinafter “Sachs”) discloses that a mechanosensitive and stretch-activated ion channel inhibitors (e.g., peptide) in an amount (e.g., 5uM, Fig. 2, [0012] of Sachs) sufficient to inhibit the mammalian cell ion channels ([0004], [0009], [0033-0034], [0036] of Sachs). The peptide is designated as GsMTx4. The enantiomer of this peptide is designated herein as D-GsMTX4. The L-form of GsMTX4 peptide is referred to herein as GsMTx4 or as the wild type GxMTX4 or L-GsMTX4 ([0008] of Sachs). The amino acid sequence of this peptide is disclosed in SEQ ID NO:1 ([0008] of Sachs) is 100% identical to the instant claim sequence of GsMTX4 (see the attached ABSS Amino acid sequence alignment report).
The prior art does not support to identify a method to inducing any non-pluripotent mammalian cell into pluripotent stem cell comprising any MSAIC inhibitors in any amount sufficient to the ion channel of any nPMC; or any CRA in any amount sufficient to reduce the cholesterol level of any nPMC; or any sECM having a Young's elastic modulus of 20 kPa or less. Accordingly at the time of filling any MSAIC inhibitors in any amount sufficient to the ion channel of any nPMC; or any CRA in any amount sufficient to reduce the cholesterol level of any nPMC; or any sECM having a Young's elastic modulus of 20 kPa or less is not well established and POSITA cannot predictably identify a method that exercise in this invention to any MSAIC inhibitors in any amount sufficient to the ion channel of any nPMC; or any CRA in any amount sufficient to reduce the cholesterol level of any nPMC; or any sECM having a Young's elastic modulus of 20 kPa or less that exercise in this invention to induce any non-pluripotent mammalian cell into pluripotent stem cell.
Therefore, it concludes that the claimed genus of any MSAIC inhibitors in any amount sufficient to the ion channel of any nPMC; or any CRA in any amount sufficient to reduce the cholesterol level of any nPMC; or any sECM having a Young's elastic modulus of 20 kPa or less to induce any non-pluripotent mammalian cell into pluripotent stem cell doesn't have an adequate written description. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed in claim 1 and dependent claims 2-4, 6-7, 9-12 and 15.
Subject matter free of art.
Current application claimed a method to induce any non-pluripotent mammalian cell into pluripotent stem cell. In the closest prior art, Yu teaches a method to produce an induced pluripotent stem cell (e.g., NPC1 iPSCs) from non-pluripotent mammalian (i.e., patient dermal fibroblasts; cited as a non-pluripotent mammalian cell in the instant specification p. 11 [0034] 26 ¶136 of Yu) and the differentiation of NPC1 iPSCs to NSCs and subsequently neurons for evaluation of drug efficacy (abstract and p. 1165 left-hand column, 2nd ¶ of Yu). Further, Yu discloses that the cell cholesterol reducing agents (i.e., methyl-[Symbol font/0x62]-cyclodextrin (M[Symbol font/0x62]CD)) in an amount (e.g., 300µM or 0.3mM) sufficient to reduce the mammalian cell cholesterol level (Fig. 4C and p. 1168, right-hand column, 2nd ¶ of Yu). This is contrary from instant method claims, because, current application claimed to induce any non-pluripotent mammalian cell into pluripotent stem cell comprising mechanosensitive and stretch-activated ion channel (MSAIC) inhibitors in a concentration of about 5 μM (instant claim 5) and M[Symbol font/0x62]CD in concentration of about 5 mM (instant claim 8). Yu does not teach or fairly suggest to to induce any non-pluripotent mammalian cell into pluripotent stem cell, wherein the MSAIC inhibitors and M[Symbol font/0x62]CD in a concentration of about 5μM and 5mM respectively.
Claims 5 and 8 are objected because art does not teach or reasonably suggest the MSAIC inhibitors and cholesterol reducing agent (M[Symbol font/0x62]CD) amount. Since claims 5 and 8 depends from rejected base independent claim 1, accordingly, 5 and 8 are likewise objected to as depend from claim 1. Claim 1 would be free of the art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 02 September 2025 are acknowledged.
The rejection of claims 1-12 as obvious over 35 U.S.C. 103 has been withdrawn considering Applicant’s remarks and the evidence of claimed method presented surprisingly superior efficacy compared to the methods of cited prior arts. Therefore, Applicant’s arguments are moot.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684