DETAILED ACTION
Notice of Pre-AIA or AIA Status
The text of those sections of Title 35, U.S. Code not included in this action can
be found in a prior Office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to the papers filed on 06/03/2026. Claims 1, 4-14, and 17-21 are currently pending as per claims filed on 06/03/2026. Claims 2, 3, 15, and 16 are cancelled and Claim 1 and 9 have been amended by Applicants’ amendment filed on 06/03/2026. Claims 12-14 and 17-21 are withdrawn.
Therefore, claims 1 and 4-11 are under examination to which the following grounds of rejection are applicable. Claim 1 is an independent claim.
Priority
The instant application claims domestic benefit to US provisional patent application number 63/388,129 filed on 07/11/2022 and US provisional patent application number 63/401,014 filed on 08/25/2022.
Thus, the earliest possible priority for the instant application is 07/11/2022.
Response to Arguments
Withdrawn objections/rejection in response to Applicants’ arguments or Amendment
Claim Objections
In view of Applicants’ amendment of claim 1 and 9, the claim objection has
been withdrawn.
Claim Rejections - 35 USC § 102
In view of Applicants’ amendment of claim 1, the claim rejections under 35
U.S.C. 102 as being anticipated by Lee et al (Biology of Blood and Marrow Transplantation, 2014, pages 1282-1289) as evidenced by Kim et al (Nature Cell Biology, 2011, pages 132-142; hereinafter "Kim 2011") has been withdrawn. Applicant amended the claim to recite specifically that the method is for increasing the longevity of specifically an iPSC-EC population, thus overcoming the rejection.
In view of Applicants’ amendment of claim 1, the claim rejections under 35
U.S.C. 102 as being anticipated by Ting-Ting et al (Biochemical and Biophysical Research Communications, 2019, pages 826-834) has been withdrawn. Applicant amended the claim to recite specifically that the method is for increasing the longevity of specifically an iPSC-EC population, thus overcoming the rejection.
Claim Rejections - 35 USC § 103
In view of Applicants’ amendment of claim 1, the claim rejections under 35
U.S.C. 103 as being unpatentable over Jiang et al (Stem Cells and Development, 2015, pages 2740-2745; cited in IDS) and further in view of Fu et al (RSC Advances, 2018, pages 23947- 23962), Fan et al (Autophagy, 2017, pages 41-56), Kim et al (Experimental & Molecular Medicine, 2016, pages 1-12; hereinafter "Kim 2016"), and Lee et al (Biology of Blood and Marrow Transplantation, 2014, pages 1282-1289) has been withdrawn. Applicant amended the claim to recite specifically that the method is for increasing the longevity of specifically an iPSC-EC population, thus overcoming the rejection.
New objections/rejection in response to Applicants’ arguments or Amendment
Claim Objections
The amendment to the claims filed on 06/03/2026 does not comply with the requirements of 37 CFR 1.121(c) because changes in the texts of cancelled claim 3 filed on 06/03/2026 was not completely marked with respect to the previously presented claims, filed on 02/18/2026. Specifically, claim 3 is not identified with the proper status in the claim listing. Amendments to the claims filed on or after 02/18/2026 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
Any further claim amendments must comply with 37 CFR 1.121(c) or they may not be entered.
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 and 4-11 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.
M.P.E.P. § 2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number
of species by actual reduction to practice (see i)(A), above), reduction to drawings (see
i)(B), above), 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 i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
Further, the written description inquiry is limited to that which is contained within the four corners of the specification, not the extent to which the skilled artisan, given his or her
knowledge of the art, would have considered it to expand with only routine
experimentation. See Ariad Pharms. Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en banc); see also id. at 1352 (“[I]t is the specification itself that must
demonstrate possession A description that merely renders the invention obvious does
not satisfy the requirement.").
Claim 1 is directed to a method of increasing longevity of an iPSC-EC population comprising stimulating, in any manner, mTOR-independent ULK1-mediated autophagy in the cells.
There is not structure/function correlation for the claimed genus of any method of stimulating mTOR-independent ULK1 mediated autophagy in cells such that they can increase the longevity of an iPSC-EC population. Rather, the only structure/function correlation present is a method of administering Rg2 during in vitro culture to increase the longevity of iPSC-ECs. The specification does not contemplate the method comprising any method of administration (i.e. that it could be administered in vivo and in vitro) or any agent that stimulates mTOR-independent ULK1-mediated signaling other than Rg2 (specification, page 21, lines 13-30; Example 2, page 22; Figure 5A-C and Figure 6A-C). Thus, the specification only teaches methods of increasing the longevity of iPSC-ECs comprising contacting the iPSC-ECs in an in vitro culture environment with the agent Rg2 such that mTOR-independent ULK1-mediated autophagy is stimulated in the iPSC-ECs.
The specification does not disclose that any other type of agent, other than Rg2, would result in the function of increasing longevity in iPSC-ECs, nor that any administration/contact of the agent with the iPSC-ECs would elicit this result other than in an in vitro culture environment. Therefore, it is unclear if the disclosed method will provide the same function as the disclosed invention.
The prior art discloses the unpredictability of using mTOR-independent, ULK-mediated autophagy approaches for modulating cell death. For instance, Liu et al (cancers, 2020, pages 1-23) teaches that ULK1 activation can promote autophagy in some cell types, but can also promote cell death, as it was shown that administration of ULK1 activators induce autophagy-associated cell death (page 7, 3.2. Activation of ULK1-Mediated Autophagy for Cancer Treatment). Liu also teaches that compounds such as clove, activate AMPK/ULK1 pathway and inhibit tumor growth, indicating modulation of autophagy and decreasing cell longevity. Thus, the prior art indicates that stimulating mTOR-independent ULK1-mediated autophagy can negatively effect cells such that longevity is decreased via cell death.
Applicant were referred to the guidelines for Written Description Requirement
published January 5, 2001 in the Federal Register, Vol.66, No.4, pp.1099-1110 (see
http://www.uspto.gov). The disclosure of a single species is rarely, if ever, sufficient to
describe a broad genus, particularly when the specification fails to describe the features
of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue
Pharma L. P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000). The possession may
be shown by actual reduction to practice, clear depiction of the invention in a detailed
drawing, or by describing the invention with sufficient relevant identifying characteristics
(as it relates to the claimed invention as a whole) such that a person skilled in the art
would recognize that the inventor had possession of the claimed invention. See, e.g.,
Pfaff v. WellsElectronics, Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,
1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai
Pharmaceutical, 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991).
The “written description” requirement may be satisfied by using such descriptive
means as words, structures, figures, diagrams, formulas, etc., that fully set forth the
claimed invention. See Noelle v. Lederman, 355 F.3d 1343, 1349, 69 USPQ2d 1508,
1514 (Fed. Cir. 2004) and Lockwood v. American Airlines, Inc., 107 F.3d at 1572, 41
U.S.P.Q.2d at 1966. A definition by function alone “does not suffice” to sufficiently describe a coding sequence “because it is only an indication of what the gene does,
rather than what it is.” Regents of the University of California v. Eli Lilly & Co., 119 F.3 at
1568, 43 USPQ2d at 1406 (Fed. Cir. 1997) (discussing Amgen Inc. v. Chugai
Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016 (Fed. Cir. 1991)). In Fiers v.
Ravel, 984 F.2d at 1169-71, 25 U.S.P.Q.2d at 1605-06 (1993), the CAFC found that “a
mere wish or plan for obtaining the claimed chemical invention” is not sufficient to
describe a chemical invention (discussed in Eli Lilly at 1404).
In the instant application, the only method disclosed is for increasing longevity of a population of iPSC-ECs comprising administering Rg2 during in vitro culture of iPSCs-ECs to stimulate mTOR-independent ULK1-mediated autophagy in the iPSC-ECs. Therefore, the limited disclosure in the specification is not deemed sufficient to reasonably convey to one skilled in the art that the applicants were in possessions of the huge genera of agents that would stimulate mTOR-independent ULK1-mediated autophagy of iPSC-ECs recited in the claims at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genera.
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.
Claim 1 and 4-11 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 1 recites the limitation "stimulating mammalian target of rapamycin (mTOR}-independent unc-51-like autophagy activating kinase 1 (ULK1)- mediated autophagy in the cells" in line 2-4. There is insufficient antecedent basis for the phrase “the cells” in the claim. Appropriate correction is required.
Claims 4-11 inherit these deficiencies insofar as they depend from claim 1.
Claim Rejections - 35 USC § 102
Claim(s) 1, 4-9, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hekman et al (JVS-Vascular Science, 2020, page 254) as evidenced by Kim et al (Experimental & Molecular Medicine, 2016, pages 1-12; as cited in office action mailed 04/01/2026; hereinafter "Kim 2016").
The applied Hekman reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1). The publication dated for Hekman is 26 December 2020. The earliest effective filing date of the instant application is 11 July 2022.
Therefore, rejection under 35 U.S.C. 103 CANNOT be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)© establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Because the reference qualifies as prior art under 102(a)(1), the provisions of MPEP 717.02 do not apply.
Regarding claim 1, 4-9, and 11, Hekman teaches stimulating mammalian target of rapamycin-independent ULK1-mediated autophagy with Rg2 (a plant-based small molecule) improved the longevity of iPSC-ECs in culture by significantly improving proliferative capacity of iPSC-ECs over multiple passages (page 254, right col, para 1-2; conclusion), hence anticipating a method of increasing the longevity of an induced pluripotent stem cell-derived endothelial cell (iPSC-EC) population comprising stimulating mammalian target of rapamycin (mTOR)-independentunc-51-like autophagy activating kinase 1 (ULK1)- mediated autophagy in the cells (claim 1), administering an agent to the cell population to stimulate mTOR independent ULK1-mediated autophagy (claim 4), wherein the agent is a small molecule (claim 5), wherein the cell population is cultured in the presence of the agent (claim 6), wherein the indirect activator is Rg2 (claim 9), and wherein the agent is an activator of unc-51-like autophagy activating kinase 1 (ULK1).
Regarding claim 7 and 8, while Hekman does not explicitly recite wherein the agent is an AMPK activator and the AMPK activator is an indirect activator, respectively, Kim 2016 teaches ginsenosides, including Rg2, have been reported to activate AMPK (left col, para 1, page 6) and “these compounds are likely to activate AMPK via AMP-dependent mechanisms” (i.e. indirect activation; ginsenosides are listed in as indirect activators in Table 1 Indirect AMPK activators). Hence, the Rg2 compound of Hekman anticipates claims 7 and 8.
Claim Rejections - 35 USC § 103
Claims 1 and 4-11 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al (Stem Cells and Development, 2015, pages 2740-2745; cited in IDS) and Kwon et al (Molecules and Cells, 2017, pages 607-612) and further in view of Fu et al (RSC Advances, 2018, pages 23947- 23962), Fan et al (Autophagy, 2017, pages 41-56; as cited in office action mailed 04/01/2026), Kim et al (Experimental & Molecular Medicine, 2016, pages 1-12; as cited in office action mailed 04/01/2026; hereinafter "Kim 2016"), and Lee et al (Biology of Blood and Marrow Transplantation, 2014, pages 1282-1289; as cited in office action mailed 04/01/2026) This rejection is a new rejection in consideration of the applicant's amendment filed on 06/03/2026.
Regarding claim 1, 4-9, and 11 Jiang teaches “endothelial cells (ECs) that are derived from iPSCs could be used in vascular repair and regeneration”, however “early senescence, limited cell proliferation, and instability of the endothelial phenotype remain significant challenges to the large-scale production and wide use of these cells” (page 1, Introduction, para 1). Jiang teaches that overexpression of the SIRT1 gene via lentiviral vector transfection in iPSC-ECs maintains EC phenotype, function, and proliferative capacity by overcoming early cell senescence (abstract, page 1), hence Jiang teaches a method of increasing longevity of an iPSC-EC population.
Jiang does not teach that the method comprises stimulating mTOR-independent ULK1-mediated autophagy of cells (claim 1), administering an agent to stimulate mTOR independent LK1-mediated autophagy (claim 4), the agent is a small molecule (claim 5), the cell population is cultured in the presence of the agent (claim 6), the agent is an AMPK activator (claim 7), is an indirect activator (claim 8), is Rg2 (claim 9), and is an activator of ULK1 (claim 11).
However, one of ordinary skill in the art would have considered the teachings of
Kwon, Fu, and Fan as these references are analogous prior art pertaining to the role of autophagy in cell senescence and the therapeutic plant compound Rg2’s ability to upregulate SIRT1 and activate autophagy independently of mTOR in in vitro cell culture conditions.
Kwon teaches that autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting an intimate relationship (abstract, left col, page 607) and autophagy suppresses cellular senescence by removing damaged macromolecules or organelles (abstract, left col, page 607). Fan teaches pharmacological strategies to activate autophagy are needed to treat disease and many compounds are difficult and highly costly to synthesize (page 41, left col, para 1). Moreover, Fan teaches that using plant compounds is a desirable alternative as they are “a natural reservoir of molecules for drug discovery” (page 41, right col, para 1) and Rg2, a ginsenoside, “is a novel AMPK activator and induces autophagy through activation of the AMPK-ULK1 pathway, but not by inhibition of mTOR” (i.e. mTOR-independent) (abstract, page 41). Fu teaches that 20(S)-ginsenoside Rg2 confers a cardioprotective effect by improving post-ischemic cardiac function, reducing the apoptotic index, and upregulating SIRT1 (abstract, page 23947).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the method of overexpression of SIRT1 to increase longevity of iPSC-ECs, as taught by Jiang, to instead use Rg2 in the culture conditions as Fu taught that Rg2 was capable of upregulating SIRT1, hence would similarly elicit an increase in the longevity of iPSC-ECs. Moreover, Kwon teaches that autophagy suppresses cell senescence, providing a motivation to target autophagy in cell senescence iPSC-ECs from Jiang. Fan taught that Rg2 is an AMPK activator and induces autophagy through activation of the AMPK-ULK1 pathway, independently of mTOR during in vitro cell culture conditions, and plant compounds are a desirable alternative in drug discovery further providing motivation to use Rg2 instead of SIRT1 overexpression to increase longevity of iPSC-ECs. As use of Rg2 during in vitro cell culture and its effects of upregulating SIRT1 and inducing autophagy through activation of the AMPK-ULK1 pathway were known in the art, one would have a reasonable expectation of success.
Additionally, it is noted that the In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). It is noted that, if the prior art discloses identical chemical structure, the properties applicant discloses and/or claims are necessarily present, In re Spada, 911 F.2d 705, 709, 15 USPQ2d. As such, the functional limitations would be present in the identical compound taught by Fu and Fan (i.e. the Rg2 which is capable of upregulating SIRT1 and does so by activating AMPK) and would therefore elicit the effects of stimulating mTOR-independent ULK1-mediated autophagy whenever it is administered to iPSC-ECs since Jiang taught that SIRT1 upregulation increases iPSC-EC longevity and Fu teaches that Rg2 upregulates SIRT1. Therefore, the method performed by Jiang, Fu, and Fan anticipates the instant claims.
Regarding claims 8 and 9, while Jiang, Kwon, Fu, and Fan do not explicitly teach Rg2 being an indirect activator, Kim 2016 teaches ginsenosides, including Rg2, have been reported to activate AMPK (left col, para 1, page 6) and “these compounds are likely to activate AMPK via AMP-dependent mechanisms” (i.e. indirect activation; ginsenosides are listed in as indirect activators in Table 1 Indirect AMPK activators). Hence, the Rg2 compound taught by Fu and Fan inherently anticipates claims 8 and 9.
Regarding claim 10, the teachings of Jiang, Kwon, Fu, and Fan render obvious claims 1, 4, and 7. However, the combined teachings do not teach the AMPK activator is a direct activator.
Lee teaches a method of enhanced long-term repopulation capacity (i.e longevity) of hematopoietic stem/progenitor cells (HSPCs) by pre-conditioning (i.e. culturing/stimulating/exposing) with a small molecule AMPK activator (AICAR) (abstract, page 1) and AICAR is a direct activator, as evidenced by Kim 2016 (page 6, right col, 5-Aminoimidazole-4-carboxamide riboside).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of a method of increasing iPSC-EC longevity by culturing iPSC-ECs in the presence of an indirect AMPK activator such as Rg2 as taught by Jiang, Fu, and Fan to instead use a direct activator such as AICAR as taught by Lee since Lee teaches that AICAR can increase longevity in hematopoietic stem/progenitor cells (HSPCs). One would be motivated to do so to increase overall yield of iPSC-ECs through increased longevity/proliferation of the iPSC-ECs and since the use of AICAR in in vitro cell culture was known in the art, one would have a reasonable expectation of success.
Response to Applicant’s arguments as they apply to rejection of claims 1 and 4-11 under 35 USC § 103
Applicant’s arguments filed 06/03/2026 have been fully considered but not persuasive.
Applicant asserts that 1) the stated motivation: that iPSC-ECs have limited proliferative capacity, would benefit from longevity-enhancing methods, and that culturing of iPSC-ECs and methods to increase cell viability are known in the art, is not a satisfactory motivation to combine references, 2) there is no motivation, teaching, suggestion, or reasonable expectation of success when combining the references as pathway behavior, particularly autophagy modulation, between cell types is unpredictable and 3) Rg2, acting through the mTOR-independent AMPK-ULK1 pathway, demonstrated a statistically significant improvement in iPSC-EC proliferative capacity over serial passages and that beneficial effect was blocked in a dose-dependent manner by the ULK1 kinase inhibitor SBI- 0206965, confirming mechanistic specificity which was an unexpected result.
Regarding argument 1), the prior art of Jiang teaches that iPSC-ECs suffer from early senescence and that this limitation hinders the proliferative capacity of iPSC-ECs and high proliferative capacity is imperative to scaling production and expanding use of these cells, thus Jiang does indeed provide motivation to seek methods to enhance longevity/proliferation. Jiang teaches the method of overexpressing a gene (SIRT1) via lentiviral transduction as a method for enhancing longevity and Fu teaches that Rg2 indeed increases SIRT1 expression, hence providing a suggestion to use Rg2 to increase SIRT1 expression in iPSC-ECs. The prior art of Lee teaches a method of enhancing longevity of hematopoietic stem cells by exposing hematopoietic stem cells to AICAR which is an AMPK activator. While Lee does not teach iPSC-ECs, the overall concept of using AICAR to improve proliferation of a subtype of stem cells was demonstrated by Lee, thus providing a basis to use AICAR in iPSC-ECs for the purpose of increasing longevity/proliferation. Furthermore, there is no evidence to suggest that AICAR does not stimulate ULK-mediated autophagy independent of mTOR. Although Lee shows proliferation of hematopoietic stem cells in vivo, the prior exposure of hematopoietic stem cells in vitro to AICAR was shown to enhance cell repopulation in vivo nonetheless. Hence, the known issue of low proliferative capacity of iPSC-ECs, SIRT1 expression increasing cell proliferation/longevity and the known successful approach of using AICAR to enhance repopulation/proliferation/longevity in an alternative stem cell type, would have led one of ordinary skill in the art to combine the references and arrive at the claimed invention of a method of increasing longevity in iPSC-ECs by using as AMPK activator, such as Rg2 or AICAR, which stimulates autophagy in an mTOR-independent ULK-mediated manner.
Regarding argument 2, while the examiner acknowledges applicant’s assertation that behavior of a signaling pathway in one cell type frequently does not predict its behavior in another, it is noted that claim 1 recites the phrase “comprising” indicating that mTOR-independent ULK1-mediated autophagy, as well as mTOR-independent ULK1-mediated autophagy could be occurring simultaneously while employing the claimed method. Furthermore, the art of Kim 2011 indicates that while active AMPK relieves mTOR-mediated suppression of AMPK, as recited in Applicant Remarks page7, active AMPK can also directly phosphorylates ULK1 which then causes autophagy (See Figure 8 below). Despite Kim 2011 teaching the need for low glucose conditions to activate AMPK (as seen in Figure 8), the claims as written do not preclude that the method of increasing the longevity of an iPSC-EC cell population cannot occur in low glucose conditions.
Figure 8 from Kim 2011
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As claim 1 recites “comprising”, the action of both AMPK-mediated direct phosphorylation of ULK1 (mTOR-independent) and AMPK-mediated inhibition of mTOR (mTOR dependent) process can concurrently occur. The examiner additionally notes that the Applicant’s remarks on page 7 lists autophagy and mitophagy modulators that did not elicit the function of increasing longevity of iPSC-EC cell populations despite their known function in autophagy pathways, however none of the modulators listed are those shown in the examiner’s cited prior art. Additionally, while the examiner acknowledges that the specification indeed discloses the panel of autophagy and mitophagy modulators (mTOR-independent ULK1-kinase mediated autophagy improves iPSC-EC proliferation, page 21, lines 6-30), this argument is not found persuasive because it is noted that the features upon which applicant relies (i.e., known autophagy modulators tested) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993).
Regarding argument 3, the statistically significant improvement in iPSC-EC proliferative capacity over serial passages and that beneficial effect was blocked in a dose-dependent manner by the ULK1 kinase inhibitor SBI- 0206965 is not found persuasive because it is noted that the features upon which applicant relies (i.e. having statistically significant improvement in iPSC-EC proliferative capacity) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). This is the case here. The claims do not recite the requirement of improved proliferative capacity such that is blocked in a dose dependent manner by the ULK1 kinase inhibitor SBI- 0206965.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIANA IRENE CANDELARIA/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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