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 .
The claims filed 4/21/2026 are under consideration.
The amendments and arguments presented in the papers filed 4/21/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 1/26/2026 listed below have been reconsidered as indicated.
a) The objection of the specification is withdrawn in view of the amendments to the specification.
b) The rejections of claims 1-6 and 8-10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of the amendments to the claims.
c) The rejection of claim 8 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn in view of the amendments to claim 8.
d) The rejections of: claim(s) 1-6, 8 and 10 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Velasco (WO 2020/243657 A1); and claim(s) 9 under 35 U.S.C. 103 as being unpatentable over Velasco (WO 2020/243657 A1), are withdrawn because Velasco does not teach a “multi-tissue organoid” as defined in para. 33 of the original specification.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection are detailed below.
Election/Restrictions
Applicant elected with traverse Group I, claims 1-6 and 8-10, in the reply filed on 11/4/2025.
Claims 7 and 11-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Priority
The present application claims priority to US provisional application 63/291,045 (filed 12/17/2021).
Priority is recognized.
While the ‘045 provisional application does not use the term “multi-tissue organoids”, the subject matter was disclosed as described by the Remarks (p. 15-16).
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the body the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Claim Interpretation
The steps of claim 1 are interpreted as not being performed in the order they are listed. While some steps, such as c, are performed after previously recited steps, i.e., steps a and b, not all the step refer to elements of a previously recited step.
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.
Claim 3 is 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.
The following are new rejections.
Regarding claim 3, the claim states “the data generated in (e) identifies association of a genetic variant with a molecular phenotype or an expression quantitative trait loci (eQTL)”. The claim sets forth an intended result and/or property of the data generated in (e). It is unclear what additional elements, if any, are required in order achieve the intended result and/or confer the property. It is further unclear, based on the use of the passive voice, if the claim is intended to require an additional active method step of “identifying an association of a genetic variant with a molecular phenotype or an expression quantitative trait loci (eQTL) using the data generated in (e)”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 3 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 2, the claim recites “the first PSC or second PSC is an induced PSC (iPSC)”. The language is describing the PSC used in forming multi-tissue organoids. The instant specification defines an “multi-tissue organoid” in para. 33 as being “derived from an iPSC”. Thus, the PSCs described in claim 1 as being used to form “multi-tissue organoid” are iPSC in view of the specification. Claim 2 fails to further limit claim 1 when properly interpreted in view of the specification.
Regarding claim 3, the claim states “the data generated in (e) identifies association of a genetic variant with a molecular phenotype or an expression quantitative trait loci (eQTL)”. The language does not include any additional active method steps nor does it further limit any aspect of (e). Thus, the claim fails to further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 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) 1-6 and 10 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Han (Genome Biology. 2018. 19:47, 19 pages).
Regarding claim 1, Han teaches forming first and second “multi-tissue organoids” or embryoid bodies from PSC derived from H9 and H1 cells. Alternatively, Han teaches first and second “multi-tissue organoids” or embryoid bodies cultured over 4 days and 8 days, respectively. See p. 14 of 19, Cell culture and differentiation. The embryoid bodies have cells of all three germ layers (Fig. 1).
Han teaches the embryoid bodies were allowed to differentiate in a particular media (p. 15 of 19, left column).
Han teaches carrying out scRNA-seq to collect transcriptomic data regarding the embryoid cells (p. 3 of 19, scRNA-seq analysis of hPSCs and EBs; and p. 15 of 19, Single-cell capture and scRNA-seq library preparation) as encompassed by step (e) and aspects of step (d).
Han teaches clustering and annotating cells based on the sequencing data and expression matrices (p. 16 of 19, Sequencing data analysis) as encompassed by parts (1), (2) and (3) of step (d). See also, Fig. 4, 5 and 6.
Han further teaches comparing the expression data between “multi-tissue organoids” in Fig. 2 and 4 and 5 and 6.
Regarding claim 2, Han teaches the induced PSC was derived by resetting H9 and H1 cells (p. 14 of 19, Cell culture and differentiation).
Regarding claim 3, the claim does not include any additional active method steps nor does it further limit any aspect of (e).
Han anticipates claim 3 for the same reason as claim 1.
Regarding claim 4, as noted above, Han uses scRNA-seq.
Regarding claim 5, as noted above, Han analyzed embryoid bodies from PSC derived from H9 and H1 cells and at days 4 and 8. This results in the analysis of at least different 4 embryoid bodies using the method describe above. These samples satisfy the elements of claim 5 requiring at least 3 different “multi-tissue organoids” being analyzed.
Regarding claim 6, Han teaches “topic modeling” in their sequencing data analysis (p. 16 of 19), as broadly encompassed by the claim in view of para. 36 of the instant specification.
Regarding claim 10, Han teaches scRNA-seq as noted above, which provides transcriptomic data for each of the cells.
Claim Rejections - 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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Han (Genome Biology. 2018. 19:47, 19 pages) in view of Mandal (Toxicology in Vitro. 2018. 46:66-76).
Regarding claim 8, Han teaches forming first and second “multi-tissue organoids” or embryoid bodies from PSC derived from H9 and H1 cells. Alternatively, Han teaches first and second “multi-tissue organoids” or embryoid bodies cultured over 4 days and 8 days, respectively. See p. 14 of 19, Cell culture and differentiation. The embryoid bodies have cells of all three germ layers (Fig. 1).
Han teaches the embryoid bodies were allowed to differentiate in a particular media (p. 15 of 19, left column).
Han teaches carrying out scRNA-seq to collect transcriptomic data regarding the embryoid cells (p. 3 of 19, scRNA-seq analysis of hPSCs and EBs; and p. 15 of 19, Single-cell capture and scRNA-seq library preparation) as encompassed by step (e) and aspects of step (d).
Han teaches clustering and annotating cells based on the sequencing data and expression matrices (p. 16 of 19, Sequencing data analysis) as encompassed by parts (1), (2) and (3) of step (d). See also, Fig. 4, 5 and 6.
Han further teaches comparing the expression data between “multi-tissue organoids” in Fig. 2 and 4 and 5 and 6.
While Han teaches the above methods, Han is silent regarding any of the embryoid bodies being from a mammal with a disease state.
Mandal teaches forming first and second “multi-tissue organoids” or embryoid bodies from human embryonic carcinoma cells that are either exposed or not exposed to ethanol (p. 67, 2.1. Cell culture and ethanol treatment), as encompassed by (a) and (b). Those exposed to ethanol represent the disease state of fetal alcohol syndrome while those not exposed to ethanol represent a disease-free state.
It would have been prima facie obvious to the ordinary artisan at the time of filing to have modified the method of Han by treating the some of the embryoid body cultures with ethanol in order to model a mammal having fetal alcohol syndrome as a disease state. One would have been motivated to do so to better understand how ethanol impacts the development of the cell clusters identified by Han. The modification has a reasonable expectation as it simply involves an additional sample to be analyzed via scRNA-seq.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Han (Genome Biology. 2018. 19:47, 19 pages).
Regarding claim 9, Han teaches forming first and second “multi-tissue organoids” or embryoid bodies from PSC derived from H9 and H1 cells. Alternatively, Han teaches first and second “multi-tissue organoids” or embryoid bodies cultured over 4 days and 8 days, respectively. See p. 14 of 19, Cell culture and differentiation. The embryoid bodies have cells of all three germ layers (Fig. 1).
Han teaches the embryoid bodies were allowed to differentiate in a particular media (p. 15 of 19, left column).
Han teaches carrying out scRNA-seq to collect transcriptomic data regarding the embryoid cells (p. 3 of 19, scRNA-seq analysis of hPSCs and EBs; and p. 15 of 19, Single-cell capture and scRNA-seq library preparation) as encompassed by step (e) and aspects of step (d).
Han teaches clustering and annotating cells based on the sequencing data and expression matrices (p. 16 of 19, Sequencing data analysis) as encompassed by parts (1), (2) and (3) of step (d). See also, Fig. 4, 5 and 6.
Han further teaches comparing the expression data between “multi-tissue organoids” in Fig. 2 and 4 and 5 and 6.
While Han teaches RNA-seq and a transcriptome analysis, Han does not specifically teach data generated for the genome of the “multi-tissue organoids”.
However, RNA-seq provides information regarding the genome of the cells of the “multi-tissue organoids” that reflects any coding sequence variations and the structure of the genome regarding whether it is in an open or closed state related to gene expression.
Thus, claim 9 is an obvious variant of the methods of Han.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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