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
Election/Restriction
Applicant’s election of Group II, claims 20-23, drawn to a system (examined as a device) configured to perform the method of modulating nephron differentiation, in the reply filed on 08/26/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-19 and 24-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Status
Claims 1-25 are pending.
Claims 1-19 and 24-25 are withdrawn.
Claims 20-23 are considered on the merits.
Priority
This application is a 371 of PCT/US2023/067804 (filed on 06/02/2023), which claims benefit from provisional application 63/365,790 (filed on 06/03/2022). The priority claim of the instant application has been granted and the earliest benefit date is 06/03/2022 from the application 63/365,790.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/12/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Specification Objections
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., p. 39-42 and 46). Applicant is required to amend or delete the embedded hyperlink and/or other form of browser-executable code. For example, “www” can be replaced with “world wide web” and “http” can be replaced with “hypertext transfer protocol” as the URL code. See MPEP § 608.01.
Claim Objections
Claims 21 and 23 are objected to because of the following informalities:
Claim 21 recites the phrase “a nephron progenitor cell or a cell of a cell aggregate”. Since indirect base claim 1 recites “at least one nephron progenitor cell” and “primitive nephron aggregate”, it is recommended to change the phrase to “the at least one nephron progenitor cell or a cell of the primitive nephron aggregate”.
Claim 23 similarly recites the phrase “a nephron progenitor cell”. It is recommended to change the phrase to “the at least one nephron progenitor cell”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 20-23 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 20 is dependent on withdrawn Claim 1. Instant Claim 20 is indefinite because it refers to the limitations of the withdrawn claim, thus lacks antecedent basis. Examiner suggests to make claim 20 independent by listing all the limitations of the withdrawn claim. Claims 21-23 are rejected as being dependent from claim 20 but not resolving the ambiguity.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
In the instant case, the limitations in claim 20 “the system configured to perform the method of claim 1 (for effecting a change in mechanical stress experienced by a nephron progenitor cell)” and claim 21 “a manipulator configured to exert a mechanical stress on a nephron progenitor cell” are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, and are limited by the description in the specification, especially in instant claims 2-7 and 11-12, limiting the system or the manipulator being an extrinsic mechanic stress (comprising an external compression, an external stretching force, a vibration, a sonication, changing environmental stiffness or imparting boundary curvature), or an intrinsic mechanical stress on the nephron progenitor cell (comprising modulating a list of signal pathways), or changing in stress of one accessory cell in mechanical communication with the nephron progenitor cell.
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.
Claims 20-22 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Garreta et al., (Nat Mater. 2019;18(4):397-405 and suppl. Fig 14).
With respect to claims 20 and 21, as discussed above, claim 20 is examined as a system configured to perform the method of modulating nephron differentiation comprising effecting a change in mechanical stress, comprising changing application of an extrinsic mechanical stress by changing environmental stiffness, experienced by nephron progenitor cells (NPCs) so as to give rise to cell differentiation and primitive nephron aggregate formation by the NPCs. Regarding the limitation “the at least on nephron progenitor cell optionally being present in a patterned arrangement”, Applicant is reminded that claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. See MPEP 2111.04 (I). Claim 21 is examined as the system comprises a manipulator configured to exert a mechanical stress on the NPCs comprising application of an extrinsic mechanical stress by changing environmental stiffness on the NPCs.
Garreta teaches a method of fine tuning the extracellular environment that accelerates the derivation of kidney organoids from human pluripotent stem cells using functionalized polyacrylamide hydrogels of tunable stiffness (ranging from soft, 1 kPa, to very rigid, 60 kPa) as substrates for hPSC differentiation (e.g., abstract and p. 401, right col., also see Fig 4 and suppl. Fig 14). Garreta teaches “Upon differentiation under 3D organotypic culture, IM-committed cells derived on soft hydrogels began to develop RVs one day earlier (at day 7: Supplementary Fig. 16c), and resulted in the generation of more RVs than those derived on rigid hydrogels” (p. 401, right col. and see Fig. 4a,b. It is noted that renal vesicles (RVs) comprise nephron progenitor cells (NPCs), see e.g., Fig 1a for diagram of kidney organoid differentiation from hPSC in which NPC induction from IM-committed cells is from day 0 to day 5, and RV induction is from day 5 to day 8). Garreta continues to teach “day 16 kidney organoids from soft conditions developed more WT1+ glomerulus-like and LTL+ tubule-like structures than those derived from rigid conditions (Fig. 4c,d), and expressed increased mRNA levels of late-stage nephron (NPHS1, SCNN1B) and vascularization (ENDOGLIN, VEGFR) markers (Fig. 4e)” (p. 401, right col., see Fig 4c for primitive nephron aggregates having WT1+ glomerulus-like and LTL+ tubule-like structures). In summary, Garreta teaches a system (e.g., hydrogels having tunable stiffness ranging from soft, 1 kPa, to very rigid, 60 kPa) configured to perform the method of modulating nephron differentiation comprising effecting a change in mechanical stress comprising changing application of an extrinsic mechanical stress by changing environmental stiffness, experienced by nephron progenitor cells (NPCs) (i.e., by culturing the NPCs on the hydrogels with different stiffness to change the environmental stiffness experienced by the NPCs), so as to give rise to cell differentiation and primitive nephron aggregate formation by the NPCs in claim 20, and the system comprises a manipulator configured to exert a mechanical stress on the NPCs comprising application of an extrinsic mechanical stress by changing environmental stiffness on the NPCs (i.e., the manipulators being the hydrogels having different stiffness configured to exert an extrinsic mechanical stress on the cultured NPCs) in claim 21.
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With respect to claim 22, Garreta teaches hPSCs grown on soft hydrogels show reduced nuclear localization of the mechanotransduction marker Yes-associated protein (YAP) (p. 401, right col., and see Suppl. Fig. 14c attached), thus teaches the system comprises a supply of an agent (e.g., the hydrogels with different stiffness) that modulates a Yap/Taz pathway.
Accordingly, Garreta anticipates instant claims.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Garreta et al., (Nat Mater. 2019;18(4):397-405 and suppl. Fig 14) in view of Toh et al., (bioRxiv preprint, doi: https://doi.org/10.1101/2021.03.19.436118; posted March 19, 2021, p. 1-23).
Claims 20-22 are anticipated by Garreta, thus are made obvious by Garreta.
Claim 23 is directed to the system further comprising a source of illumination configured to effect an optogenetic process within the NPCs.
However, Garreta is silent on the system comprising a source of illumination for effecting an optogenetic process within the NPCs in claim 23.
Toh teaches optogenetic manipulation of YAP by an optogenetic construct (optoYAP) for manipulating YAP localisation, and consequently its activity and function (see e.g., title and abstract). Toh teaches HEK293T cells are transfected with optoYAP and subjected to 488 nm pulsatile illumination of 1 s every 30 s, and in 488 nm light, the LOV2 domain unfolds, exposing the NLS, which shuttles optoYAP into the nucleus. Nuclear import of optoYAP is reversible and tunable by light intensity. In cell culture, activated optoYAP promotes YAP target gene expression, cell proliferation, and anchorage-independent growth (e.g., abstract, see p. 3, “Characterisation of optogenetic YAP in mammalian cells” and Fig 1 for nuclear shuttling, see p. 4, “Functionality of nuclear-localised optoYAP” and Fig 3a, b for promoting proliferation, and see p. 5 for transformed cells being able to bypass rigidity sensing). Toh teaches the illumination is by Perkin Elmer or Nikon W1 or a LED light strip (see p. 17, section “Light activation”), thus teaches a source of illumination (e.g., a LED light strip) configured to effect an optogenetic process within transfected cells, related to claim 23.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the system configured to differentiate NPCs into nephron aggregates using hydrogels with different stiffness that change YAP nuclear localization disclosed by Garreta, by substituting culturing NPCs on multiple hydrogels each having a specific stiffness with transfecting the cells with an optoYAP construct and using a source of illumination as suggested by Toh with a reasonable expectation of success. Since Garreta cultures NPCs on multiple hydrogels with different stiffness that results in different nuclear localization of YAP in the cells, and since Toh teaches optogenetic manipulation of YAP nuclear localization and function by transfecting the cells with an optoYAP construct, and in combination with a source of illumination, optoYAP can shuttle in and out nucleus (be activated and deactivated) that is reversible and tunable by light intensity (see above), one of ordinary skill in the art would have had a reason to make this substitution in order to take advantage of manipulating YAP function in the cultured NPCs in a reversible and tunable manner to study the nephron differentiation from NPCs in response to mechanical stress on the NPCs since YAP is the mechanotransduction marker as taught by Garreta.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Douglas (Doug) Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANJIAN ZHU/Examiner, Art Unit 1631
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