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 .
Status of Claims
Claims 1-11, 14-22, 25-26, 29, 32, 35-37, 40-42, 48-51, 58 and 79-82 are pending.
Claims 12-13, 23-24, 27-28, 30-31, 33-34, 38-39, 43-47, 52-57, and 59-78 are cancelled.
1-8 and 80-82 are examined on the merits herein.
Election/Restrictions
Applicant's election with traverse of Group I, drawn to claims 1-8, in the reply filed on 02/02/2026 is acknowledged. The traversal is on the ground(s) that Valamehr (WO 2015/134652 A1), in view of Tomizawa (Experimental and Therapeutic Medicine, 2011, 2(3): 405-408), does not render obvious claim 1 as amended because Tomizawa teaches experiments with a fibroblast-derived iPSC cell line, that are evaluated in embryoid bodies, which differ from the limitations required by amended claim 1 (p 12-13 of Remarks filed 02/02/2026). Applicant argues that all of claims 2-8, 14-20, 48-51, and 80-82 ultimately depend from claim 1, and include the technical features thereof, and therefore, as presently amended claim 1 is novel and unobvious over the cited references, the features thereof are special technical features shared by dependent claims 2-8, 14-20, 48-51, and 80-82. As such, at least claims 1-8, 14-20, 48-51, and 80-82 share special technical features and possess unity of invention (p 12-13 of Remarks filed 02/02/2026).
Upon reconsideration, Valamehr (US 2017/0073643 A1, corresponds to WO 2015/134652 A1 cited in the Restriction Requirement mailed 12/01/2025) does teach a composition that reads on the composition of claim 1. The updated Restriction Requirement, which maintains the same groupings as set forth in the Restriction Requirement mailed 12/01/2025 but with an updated discussion of the prior art and the shared technical feature of the inventive groups, is set forth below, and Applicant’s arguments are subsequently addressed.
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-8 and 80-82, drawn to a composition for iPSC production, wherein the composition does not comprise a TGFβ inhibitor.
Group II, claims 9-11, drawn to a composition for iPSC production, comprising a TGFβ inhibitor.
Group III, claims 14-20, drawn to a method of producing iPSC, using the composition of claim 1.
Group IV, claims 21-22, 25-26, 29, 32, 35-37 and 40 drawn to a method of producing iPSC, using the composition of claim 9.
Group V, claims 41-42 and 48-51, drawn to an iPSC, a cell line, a clonal population or master cell bank thereof, or a composition thereof.
Group VI, claims 58-58, and 79, drawn to an in vitro system for initiating reprogramming in a non-pluripotent stem cell.
If an application contains claims to more or less than one of the combinations of categories of invention set forth above, unity of invention may not be present. Here, the groups are not directed to one, and only one, of the above listed combination of categories. The claims are presented are directed to four distinct products and two processes of use. Where multiple products, processes of manufacture or uses are claimed, the first invention of the category first mentioned in the claims of the application and the first recited invention of each of the other categories related thereto will be considered as the main invention in the claims, see PCT Article 17(3)(a) and § 1.476(c). Therefore, Group I is considered the main product invention in the claims, and Group III is considered the main process invention in the claims. Groups I and III are related as a product and a process of use of said product.
As set forth in Rule 13.1 of the Patent Cooperation Treaty (PCT), "the international application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept." Moreover, as stated in PCT rule 13.2, "Where a group of inventions is claimed in one and the same international application, the requirement of unity of invention referred to in Rule 13.1 shall be fulfilled only when there is a technical relationship among those inventions involving one or
more of the same or corresponding special technical features." Furthermore, Rule 13.2 defines "special technical features" as "those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art."
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I and III lack unity of invention because even though the inventions of these groups require the technical feature of the composition of claim 1, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Valamehr (US 2017/0073643 A1; cited in IDS 01/08/2024). Valamehr teaches a composition for manufacturing pluripotent stem cells (e.g., Abstract; para 22, 53, 84-86, 117-118, 263, 324), wherein the pluripotent cells have ground state pluripotency (i.e., are not present in an embryoid body) (e.g., Abstract; para 4, 38-42, 70, 84-86, 103, 208-209), and wherein the composition comprises a ROCK inhibitor, a MEK inhibitor, a Wnt pathway agonist (reads on WNT activator), and does not comprise a TGFβ inhibitor (e.g., para 12, 50-52, 64, 97, 127-129, 147-149, 272). Valamehr teaches an embodiment wherein the culture medium comprises a transforming growth factor beta (TGF-β) (para 310). Therefore, the shared technical feature is not a special technical feature, and unity of invention is lacking a posteriori between the inventions of Groups I and III.
Regarding Applicant’s arguments: Applicant argues that all of claims 2-8, 14-20, 48-51, and 80-82 ultimately depend from claim 1. In response, claims 14-20 and 48-51 do not depend from claim 1. Claims 14-20 and 48-51 are drawn to a method of producing iPSCs, comprising a step of cryopreserving a population of iPSCs (claims 14-20), or to iPSCs produced thereof (claims 48-51). As set forth in the Restriction requirement set forth above, claims (1-8), (14-20), and (48-51) are each directed to distinct categories or groups of inventions. New claims 80-82 depend from claim 1, as asserted by Applicant, and are therefore examined herein as part of Group I. Because Valamehr (US 2017/0073643 A1) anticipates the product of claim 1 as set forth above, the teachings of Tomizawa (Experimental and Therapeutic Medicine, 2011, 2(3): 405-408) are no longer relied upon for the restriction requirement. Therefore, Applicant’s arguments regarding Tomizawa are moot.
The requirement is still deemed proper and is therefore made FINAL.
Claims 9-11, 14-22, 25-26, 29, 32, 35-37, 40-42, 48-51, 58, and 79 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 02/02/2026.
Priority
The instant application is a 371 of PCT/US2021/053240 filed 10/01/2021, which claims benefit of Provisional application 63/087,119 filed 10/02/2020.
Specification
The disclosure is objected to because of the following informalities: The disclosure contains a link for a website that does not exist; see para 183 at page 58. As a reminder, references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claim Interpretation
Claim 1 recites the phrase “for preparing induced pluripotent stem cells (iPSCs)” in the preamble (line 1). This is a recitation of intended use, which does not impart further structural limitations to the composition beyond the limitations recited in the body the claim, and therefore does not further limit the claim. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). See MPEP 2111.02(II).
Claim 7 recites phrase “genomic edit,” which is not defined in the specification. In the absence of a definition, the broadest reasonable interpretation of this phrase, which is “a modification of a specific sequence of A, C, G, T units that instruct the sequence of amino acids that comprise a specific protein” and includes naturally occurring gene edits, is used for the purposes of examination (see Bedford Research Foundation, 2019, “Naturally Occurring Gene Edits”).
Claim Rejections - 35 USC § 112(b)
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 2, 4, 7, and 8 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 2 is drawn to the composition of claim 1, with additional limitations as recited in options (a) – (c), with each of the options as alternatives.
Option (a) of claim 2 recites “wherein the long-term iPSC maintenance comprises one or more of stages comprising: single cell dissociation of iPSC colonies, single cell sorting of dissociated iPSCs, iPSC single cell clonal expansion, clonal iPSC master cell bank (MCB) cryopreservation, thawing of iPSC MCB, and optionally additional cryopreserve-thaw cycles of the iPSC MCB.” The stages recited in option (a) are steps in a method; however, claim 2 is drawn to a composition. Because claim 2 recites a product and additional limitations regarding a method of maintaining iPSCs, the metes and bounds of the claim are unclear and would create confusion as to when direct infringement occurs.
Option (b) of claim 2 recites “wherein the TGFβ family protein is optionally added to the composition at single cell dissociation of iPSC colonies, or at iPSC single cell clonal expansion, or at any stage in-between,” and is therefore indefinite for the same reason as set forth above for option (a). Furthermore, because each of the options (a) – (c) in claim 2 are recited as alternatives, and the entirety of option (b) recites an optional embodiment, if option (b) is chosen, claim 2 would be patentably indistinct from claim 1.
Claims 4 and 8 depend from claim 2, and are therefore included in the rejection of claim 2.
Furthermore, claim 4, which depends from claim 2, recites options (i) – (iii) as alternatives. Options (i) and (ii) of claim 4 recite “wherein the non-pluripotent cell comprises,” and option (iii) of claim 4 recites “wherein the reprogramming composition comprises.” The non-pluripotent cell and the reprogramming composition are only recited in option (c) of claim 2, and not in claim 1 or in options (a) – (b) of claim 2. Thus, if options (a) or (b) are selected for claim 2, the limitations of claim 4 would lack antecedent basis.
Furthermore, claim 8, which recites stages of a method in (i), is indefinite for the same reason as set forth above for option (a) of claim 2.
Claim 7 is drawn to “The composition of claim 1, wherein the iPSC comprises at least one genomic edit.” Claim 1 recites a plurality of iPSCs (i.e., “induced pluripotent stem cells (iPSCs),” first recited in line 1 thereof), but not an iPSC in the singular. Therefore, it is unclear whether claim 7 should be interpreted as “wherein the iPSCs comprises an iPSC comprising at least one genomic edit.” Or “wherein each iPSC comprises at least one genomic edit.” The first interpretation is the broadest interpretation of claim 7 as currently written, and will be used for the purposes of examination.
Claim Rejections - 35 USC § 112(a)
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 1-8 and 80-82 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(s) contains subject matter which 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
From M.P.E.P. § 2163, the analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.
For claims drawn to a genus, possession may be shown (for example) through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
Claim 1 is drawn to a composition for preparing induced pluripotent stem cells (iPSCs), comprising: (i) a TGFß family protein, (ii) a ROCK inhibitor, (iii) a MEK inhibitor and a WNT activator, and (iv) the iPSCs, wherein the composition does not comprise a TGFß inhibitor, wherein the composition is effective to improve iPSC pluripotency and genomic stability in a long-term iPSC maintenance, and wherein the iPSCs (a) are not present in an embryoid body, or (b) are iPSCs produced from a T cell. The product of claim 1 recites a structure: a composition comprising (i) a TGFß family protein, (ii) a ROCK inhibitor, (iii) a MEK inhibitor and a WNT activator, and (iv) iPSCs, wherein the composition does not comprise a TGFß inhibitor, and wherein the iPSCs (a) are not present in an embryoid body, or (b) are iPSCs produced from a T cell. The product of claim 1 also recites a function: wherein the composition is effective to improve iPSC pluripotency and genomic stability in a long-term iPSC maintenance. Thus, claim 1 is drawn to a product comprising a very large genus of a composition comprising a TGFß family protein, a ROCK inhibitor, a MEK inhibitor, and a WNT activator, comprising the claimed function.
Neither the specification nor the prior art establishes a structure-function relationship wherein a composition comprising (i) a TGFß family protein, (ii) a ROCK inhibitor, (iii) a MEK inhibitor and a WNT activator, and (iv) the iPSCs, wherein the composition does not comprise a TGFß inhibitor, would be capable of functioning as claimed with any degree of predictability.
Regarding the TGFß family protein: The instant specification discloses supplementing a culture medium with Activin A, TGFß, and/or Nodal (para 33), as well as functional variants or fragments thereof (para 144). The specification does not identify any other TGFß family protein that would be encompassed by the structural limitations of claim 1, and would predictably result in the claimed function of improving iPSC pluripotency and genomic stability in a long-term iPSC maintenance. As such, the instant specification does not provide a sufficient representative sampling of structures that belong to the TGFß family of proteins that are capable of providing for said function as claimed.
The prior art is unpredictable. For example, Valamehr (US 2017/0073643 A1) teaches that the culture medium taught therein, which improves the pluripotency and genomic stability of pluripotent cells cultured therein (para 38-42, 47-49, 70, 81-83, 103, 114-116, 131, 208-210, 250, 269-270, 272, 276, 376), comprises TGFß (para 310), but does not identify another TGFß family protein that could be used in the place of TGFß. Moreover, Poniatowski (Mediators of Inflammation, 2015: 137823) teaches that the TGFß superfamily is “a large and continuously expanded group of regulatory polypeptides,” comprising a model transforming growth factor beta family and other families, such as bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), activins (ACTs), inhibins (INHs), and glial-derived neurotrophic factors (GDNFs), as well as some proteins not included in the above families, such as Müllerian inhibiting substance (MIS), also known as anti-Müllerian hormone (AMH), left-right determination factor (Lefty), and nodal growth differentiation factor (Nodal) (p 2, col 1, para 1; Figure 1). Thus, the prior art cannot be relied upon for making up for the deficit of the instant specification with regard to a sufficient representative number of species that belong to the TGFß family of proteins that provide for said function as claimed.
Regarding the ROCK inhibitor: The instant specification discloses thiazovivin, Y27632, pyrintegrin, Blebbistatin, and functional variants or derivatives thereof, for use in the cell culture medium (para 116). The specification does not identify any other ROCK inhibitors that would be encompassed by the structural limitations of claim 1, and would predictably result in the claimed function of improving iPSC pluripotency and genomic stability in a long-term iPSC maintenance. As such, the instant specification does not provide a sufficient representative sampling of ROCK inhibitors that are capable of providing for said function as claimed.
The prior art is unpredictable. For example, Valamehr (US 2017/0073643 A1) teaches that the culture medium taught therein, which improves the pluripotency and genomic stability of pluripotent cells cultured therein (para 38-42, 47-49, 70, 81-83, 103, 114-116, 131, 208-210, 250, 269-270, 272, 276, 376), comprises thiazovivin, Y27632, Fasudil, AR122-86, Y27632 H-1152, Y-30141, Wf-536, HA-1077, hydroxyl-HA-1077, GSK269962A, SB-772077-B, N-(4-Pyridyl)-N′-(2,4,6-trichlorophenyl)urea, 3-(4-Pyridyl)-1H-indole, and (R)-(+)-trans-N-(4-Pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (para 17, 130, 302), but does not teach that any ROCK inhibitor can be used. Moreover, Feng (Journal of Medicinal Chemistry, 2016, 59(6): 2269-2300) teaches that as of 2015, over 170 ROCK inhibitors have been identified (Abstract), which are categorized into Type I and Type II kinase inhibitors (p 2273, col 1, para 1), and which are further categorized as classic ROCK inhibitors, indazole based ROCK inhibitors, 4-Carboxamido-aromatic Ring Substituted-Pyridine ROCK inhibitors, 4-Amido(urea or carbamate)-aromatic Ring Substituted-Pyridine (Pyrimidine, Pyrrolopyridine, etc.) and Phenoxy Substituted-Pyrrolopyridine Based ROCK Inhibitors, 4-Carboxamido-aromatic Ring Substituted Pyrazole Based ROCK Inhibitors, 4-Amido(ureido or carbamate)-aromatic Ring Substituted-Pyrazole Based ROCK Inhibitors, 4′-Alkylaromatic Ring Substituted Pyrazoles, Benzimidazole, Benzothiazole, Indazole, and Indole Substituted Pyrazole Derivatives, Quinazolinone Substituted Pyrazole Derivatives, Benzathiophene Substituted Pyridine (Pyrimidine, Pyrrolopyridine) Derivatives, Benzamide Derivatives, Aminofurazan Derivatives, 6-/7-Substituted Isoquinoline/Isoquinolinone Derivatives, and Boron Derivatives (Sections 3.1-3.14). Thus, the prior art cannot be relied upon for making up for the deficit of the instant specification with regard to a sufficient representative number of species of ROCK inhibitors that provide for said function as claimed.
Regarding the MEK inhibitor: The instant specification discloses exemplary MEK inhibitors (para 117-119), but does not establish a structure-function relationship between the enumerated MEK inhibitors and the function as recited in claim 1, and only PD0325901 is used in the Fate Maintenance Medium 2 (p 38-39, Tables 1-2). As such, the instant specification does not provide a sufficient representative sampling of WNT activators that are capable of providing for said function as claimed. Cheng (Molecules, 2017, 22(10): 1551) teaches that the MEK inhibitor targets the Ras/Raf/MEK/ERK signaling pathway, inhibiting cell proliferation and inducing apoptosis (p 1, Introduction, para 1). MEK1 and MEK 2 are closely related and participate in the Ras/Raf/MEK/ERK signal transduction cascade (p 2, para 1). Some MEK inhibitors target MEK1, whereas others target both MEK1 and MEK2 (e.g., Table 2). Thus, the prior art cannot be relied upon for making up for the deficit of the instant specification with regard to a sufficient representative number of species of MEK inhibitors that provide for said function as claimed.
Regarding the WNT activator: The instant specification provides a definition of the term “Wnt activator” (para 120) and non-limiting examples of Wnt pathway agonists (para 121). However, only GSK-3ß inhibitors are specifically listed as Wnt agonists suitable for use in the composition of claim 1 (para 122). The specification does not identify any other WNT activators that would be encompassed by the structural limitations of claim 1, and would predictably result in the claimed function of improving iPSC pluripotency and genomic stability in a long-term iPSC maintenance. As such, the instant specification does not provide a sufficient representative sampling of WNT activators that are capable of providing for said function as claimed.
The prior art is unpredictable. For example, Valamehr (US 2017/0073643 A1) teaches that the culture medium taught therein, which improves the pluripotency and genomic stability of pluripotent cells cultured therein (para 38-42, 47-49, 70, 81-83, 103, 114-116, 131, 208-210, 250, 269-270, 272, 276, 376), comprises Wnt pathway agonists, but like the instant specification, only enumerates species of GSK-3ß inhibitors (para 288-292). Moreover, Nihers (Nature Reviews Molecular Cell Biology, 2012, 13(12): 767-779) teaches that the “WNT signalling network is of bewildering complexity, containing numerous components and being subject to many regulatory steps and cross-talk mechanisms” (p 767, col 1, para 3) and that 19 WNT proteins couple to more than 15 receptors and co-receptors in seven protein families (Abstract). Broadly, WNT signaling pathways fall into either ß-catenin-dependent or ß-catenin-independent pathways (p 768, col 1-2), the former, but not latter, of which comprises GSK3 (Figure 1; p 769, col 1, para 2 – p 770, col 1, para 1). Thus, the prior art cannot be relied upon for making up for the deficit of the instant specification with regard to a sufficient representative number of species of WNT activators that provide for said function as claimed.
In conclusion, the skilled artisan would not have reasonable concluded at the time of the invention that application was in possession of the invention as claimed. Claims 2-8 and 80-82 depend from claim 1 and inherit its deficiencies, and are therefore included in the rejection.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 3, 5, 7, and 80-81 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Valamehr (US 2017/0073643 A1; cited in IDS 01/08/2024), as evidenced by Yoshihara (Cell Reports, 2017, 21: 308-315).
Regarding claim 1: Valamehr teaches a composition for manufacturing pluripotent stem cells (e.g., Abstract; para 22, 53, 84-86, 117-118, 263, 324), wherein the pluripotent cells have ground state pluripotency (i.e., are not present in an embryoid body) (e.g., Abstract; para 4, 38-42, 70, 84-86, 103, 208-209), and wherein the composition comprises a ROCK inhibitor, a MEK inhibitor, a Wnt pathway agonist (reads on WNT activator), and does not comprise a TGFβ inhibitor (e.g., para 12, 50-52, 64, 97, 127-129, 147-149, 272). Valamehr teaches an embodiment wherein the culture medium comprises a transforming growth factor beta (TGF-β) (para 310).
As the composition taught in Valamehr reads on the composition of instant claim 1, the composition of Valamehr inherently possesses the characteristics of being effective to improve iPSC pluripotency and genomic stability in a long-term iPSC maintenance, as recited in instant claim 1 (lines 8-9). Moreover, Valamehr teaches that the composition improves the pluripotency of pluripotent cells cultured therein, including from at least 5 to at least 100 passages (para 38-42, 70, 103, 131, 208-210, 269-270, 272, 276). Valamehr further teaches that the composition improves the genomic stability of pluripotent cells cultured therein, including from at least 10 to at least 100 passages (para 47-49, 81-83, 114-116, 209, 250, 270, 376).
Regarding claim 3: Valamehr teaches that the culture medium comprises a transforming growth factor beta (TGF-β) (para 310), and that the WNT activator is a GSK3 inhibitor (para 13, 50-52, 64-65, 129).
Regarding claim 5: As the composition taught in Valamehr reads on the composition of instant claim 1, the composition of Valamehr inherently possesses the characteristics recited in instant claim 5. Moreover, Valamehr teaches that the composition reduces the spontaneous differentiation of pluripotent cells cultured therein, including from at least 5 to at least 100 passages (para 105-109, 209, 269, 271-272, 276). Valamehr further teaches that genomic stability refers to the ability of a cell to faithfully replicate DNA and maintain integrity of the DNA replication process, and is indicated by the frequency of mutations and chromosomal aberrations (such as translocations, aneuploidy, copy number variations and duplications) that is substantially similar to the frequency of mutations and chromosomal aberrations relative to normal somatic human cells (para 250).
Regarding claim 7: Valamehr is silent regarding an iPCS comprising at least one genomic edit. Yoshihara shows that there are genetic variations in iPSC genomes, including de novo point mutations introduced during reprogramming from somatic cells into iPSCs (e.g., Abstract). Thus, the iPSCs used in the method of Valamehr would comprise at least one genomic edit (see Claim Interpretation).
Regarding claims 80-81: Valamehr teaches a composition for manufacturing pluripotent stem cells (e.g., Abstract; para 22, 53, 84-86, 117-118, 263, 324), wherein the pluripotent cells have ground state pluripotency (i.e., are not present in an embryoid body) (e.g., Abstract; para 4, 38-42, 70, 84-86, 103, 208-209).
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.
Claim(s) 1, 5-6, and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Valamehr (US 2017/0073643 A1), in view of Seki (Cell Stem Cell, 2010, 7(1): 11-14; cited in IDS 01/08/2024).
The teachings of Valamehr are set forth above. Valamehr anticipates claims 1 and 5.
Regarding claim 82: Valamehr does not teach the composition of claim 1, wherein the iPSCs are produced from a T cell.
Seki teaches a method of generating iPCSs from human T cells (Title, Abstract). Seki teaches that T cell-derived iPCSs have a traceable genetic signature through TCR locus rearrangement, and therefore, the descendants of T cell-derived iPCSs can be identified by analyzing their TCR rearrangement patterns, which allows for the monitoring of said cells following transplantation into patients (p 13, para 2 – p 14, col 1, para 1). Seki teaches that the method disclosed therein has advantages for research into stem cell reprogramming, TCR rearrangement, immunologic disorders, and the development of genetic markers for future applications of regenerative medicine, and that T cell-derived iPCSs may be relatively easy to use in a clinical setting (p 14, col 1, para 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Valamehr by using iPSCs produced from a T cell. One of ordinary skill in the art would have been motivated to make this modification because Seki teaches that T cell-derived iPCSs are useful in both research and clinical settings. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Seki teaches that iPCSs can be generated from T cells.
Regarding claim 6: As set forth above in the discussion for claim 82, Valamehr, in view of Seki, renders obvious the method of claim 1, wherein the iPSCs are produced from a T cell. Following the discussion for claim 1, Valamehr teaches that the composition taught therein maintains normal karyotypes and genomic stability of the pluripotent cells for at least 100 or more passages (para 250, 270, 376).
Conclusion
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/RISA TAKENAKA/Examiner, Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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