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 .
Detailed Action
Claims 1 - 18 are currently pending in the instant application. Claims 1 and 18 have been amended, claim 18 has been added and claims 9-18 have been withdrawn by Applicants’ amendment filed on 8/7/2026.
Restriction/Election
Applicant's election, without traverse, in the reply filed August 7, 2026 of Group I, claims 1 - 7, directed to an islet-like organoid expressing monSTIM1 in which insulin is regulated by light irradiation is acknowledged.
Claims 8 - 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 1 – 7 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on May 31, 2024, and December 5, 2024 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed May 31, 2024, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/KR2022/019109, filed November 29, 2022, which claims the benefit of KR10-2022-0048550, filed April 20, 2022, and KR10-2021-0170587, filed December 2, 2021.
Therefore, the earliest priority date is December 2, 2021.
Receipt is acknowledged of certified untranslated copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non- English application.
Claim objection
Claims 1 - 7 are objected to because of the following informalities: abbreviations such as monSTIM1 and AAVS1 should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Rejection - 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 1 - 7 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 is indefinite for the recitation of “wherein the islet-like organoid is derived from a stem cell into which monSTIM1 has been introduced” in lines 2 – 3. The metes and bounds of how an islet-like organoid can be derived from a stem cell and still meet the intended limitation of the claim are not clear. Without a clear statement of the process by which the starting material is derivatized, it is not possible to know the metes and bounds of a "derivative" because any given starting material can have many divergent derivatives depending on the process of derivatization. For the purpose of a compact prosecution the term “derived” recited in claim 1 has been interpreted as “obtained or isolated from.”
Claim 2 is indefinite in its recitation of “the light” in line 1. There is not proper antecedent bases for “the light” in the claim. Claim 1 recites “light irradiation”.
Claims 3 – 7 are indefinite insofar as they ultimately depend on claim 1.
Claim Rejection - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 - 7 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (hereinafter referred to as Kim 2016) ( Kim Y. et al. Sci Rep. 2016 Oct 12;6:35145; in the IDS filed May 31,2024), and further in view of Kim et al. (hereinafter referred to as Kim 2020). (Kim S. et al. Nat Commun. 2020 Jan 10;11(1):210.), as evidenced by Renaud et al. (US 20200140896 A1, published May 7, 2020), and Llanos et al. (Llanos P. et al. PLoS One. 2015 Jun 5;10(6):e0129238.. Erratum in: PLoS One. 2015 Oct 02;10(10):e0140198.).
Regarding claim 1, Kim 2016 teaches islet-like organoids derived from human pluripotent stem cells (Title and Abstract) (interpreted as an islet-like organoid, and islet-like organoid is derived from a stem cell). Kim 2016 teaches that these islet-like clusters are functionally capable of glucose responsive insulin secretion (Abstract). Kim 2016 teaches that these clusters showed Ca2+ oscillation (pg. 2, second paragraph). Kim teaches that the exocytosis of insulin vesicles from hESC-derived ECCs occurs via Ca2+ oscillation (pg. 9, second paragraph) whrere “the first influx of [Ca2+] was detected immediately after glucose stimulation” (page 9, para 2). Thus Kim 2016 teaches that “hESC-derived ECCs have ß cell-like properties in that they rapidly respond to glucose stimuli, showing both [Ca2+ ]i oscillation and insulin secretion.” (page 9, para 2).Kim 2016 does not specifically exemplify islet-like organoid expressing monSTIM1 in which insulin secretion is regulated by light irradiation.
Kim 2020 teaches ultra-light-sensitive optogenetic Ca2+ modulator, named monSTIM1 encompassing engineered cryptochrome2 for manipulating Ca2+ signaling (Abstract). Kim 2020 teaches that optogenetic Ca2+ modulator with ultra light sensitivity that can be readily activated in vivo awake mouse brain through non-invasive light illumination (pg. 2, left column, second paragraph). Kim 2020 teaches that abnormally modulated intracellular Ca2+ dynamics are correlated with brain dysfunctions such as neurodegenerative disease (pg. 2, left column, first paragraph). Kim 2020 teaches that STIM1 would contribute to the multimeric property of OptoSTIM1 without blue light, promoting constitutive Ca2+ influx through CRAC channels and leading to elevated basal Ca2+ level (pg. 2, right column, first paragraph).
Regarding claims 2 and 6, Kim 2020 teaches the cells were exposed to pulsatile illumination of light (5-s irradiation every 10-s, 470 nm, 100 μWmm−2 (pg. 8, left column, second paragraph).
Regarding claim 3, 4, and 7, Kim 2020 teaches that monSTIM1 has effective induction of Ca2+ influx (pg. 4, left column, first paragraph) (interpreted as there is an increase in Ca2+ concentration by light irradiation).
Therefore, in view of the benefits of modulating intracellular Ca2+ dynamics in mice as evidenced by Kim 2020, it would have been prima facia obvious for one of ordinary skill in the art to modify the islet-like organoids derived from human pluripotent stem cells, as taught by Kim 2016, with the optogenetic Ca2+ modulator, as taught by Kim 2020, with a reasonable expectation of success in regulating Ca2+ levels in addition to glucose stimulation inducing intracellular of Ca2+ influx, and thereby enhancing insulin secretion. It would have been prima facia obvious to combine the cited sources because Kim 2016 teaches that the exocytosis of insulin vesicles from hESC-derived ECCs occurs via influx of [Ca2+] (Ca2+ oscillation), and Kim 2020 teaches modulating the Ca2+ using monSTIM1, by light irradiation ..
Kim 2016 and Kim 2020 do not specifically teach that the monSTIM1 has been introduced at an AAVS1 gene locus (claim 1).
Although Kim 2016 and Kim 2020 do not specifically teach that the monSTIM1 has been introduced at an AAVS1 gene locus, one of ordinary skill in the art would have been able to introduce monSTIM1 at the AAVS1 gene locus of stem cells, as evidenced by Renaud et al.
Renaud et al. teaches a method of selectively treating a patient with a gene editing system, comprising introducing said gene editing system into a cell, e.g., population of cells, wherein the cells are HSPCs (claims 1 and 8). Renaud teaches that the target locus is AAVS1 (claim 14). Thus, one of ordinary skill in the art would have been able to introduce monSTIM1 at an AAVS1 gene locus.
Regarding claim 5, Kim 2016 and Kim 2020, Kim 2016 teaches that “hESC-derived ECCs have ß cell-like properties in that they rapidly respond to glucose stimuli, showing both [Ca2+ ]i oscillation and insulin secretion.” (page 9, para 2).Moreover , it is well known in the art that an increase in intracellular Ca2+ concentration is the primary trigger for glucose-stimulated insulin secretion, as evidenced by Llanos et al. (Abstract). Llanos discloses that glucose stimulated insulin secretion requires an increase in intracellular free Ca2+ concentration (abstract).
Conclusion
Claims 1 – 7 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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