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 .
Claims 36-55, of record 7/6/2026, are pending and subject to prosecution.
Election/Restrictions
Applicant's election with traverse of group I, claims 36-45, in the reply filed on 7/6/2026 is acknowledged. The traversal is on the ground(s) that the cells disclosed by Alberio et al. are fundamentally distinct from the cells of the instant application in terms of function (Applicant Remarks, page 10-13). This is not found persuasive because the instant claims do not require the performance characteristics asserted by the applicant. Independent claim 1 requires only an isolated pluripotent stem cell, having a pluripotency of pig pre-gastrulation epiblast cells, expressing one or more pluripotency markers and one or more Epiblast markers, and is capable of stable passage, as amended, for a minimum of 30 times. Alberio et al. teach passaged pig epiblast cells (which read on “isolated pluripotent stem cell, having a pluripotency of pig pre-gastrulation Epiblast cells”) that stably express the pluripotency markers OCT4, SOX2, NANOG, and NODAL from passage 5 through passage 22 (See fig. 2). The stable expression of these markers through 22 passages would reasonably suggest to one of ordinary skill in the art that further passaging of the cells, for example, to 30 passages, would be readily feasible. The cells of Alberio et al. therefore still read on and render obvious the shared technical feature of the claim groups and demonstrate that unity of invention is lacking a posteriori.
The requirement is still deemed proper and is therefore made FINAL.
Claims 46-55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 7/6/2026.
Priority
The instant application is a national stage entry of PCT/CN2022/117588 (filed 9/7/2022). Acknowledgement is made of the applicant’s claim for foreign priority to application 202111061392.9 (filed 9/10/2021 in China).
Drawings
The drawings are objected to because view number must be preceded by the abbreviation “FIG.” See 37 CFR 1.84(u). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The figure legends for fig. 5B and 5E-K identify data points by color, however, the figures are in black and white.
The use of the terms GlutaMAX, B-27, KnockOut, Neurobasal, SuperScript, AMPure, KAPA HyperPure, HiSeq, Accutase, KaryoMAX, Colcemid, BGISEQ-500, Triton X-100, Tween, RealStar, LightCycler, Immobilon, SuperSignal, NEBuffer, RNeasy, Globulin-Zero, Qubit, PiggyBac, MoFlo, and Alexa Fluor, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claims 37-41 and 45 are objected to because of the following informalities:
In claims 36, 38-39 41, and 43, “epiblast”, “hypoblast”, “ectoderm”, and “expression” should not be capitalized.
Claims 37-41 and 45 should be rewritten to recite proper Markush groupings.
In claim 41, “genes” in line 2 should be replaced with “a gene”, and “specific “ should be inserted before “interaction” in line 13.
In claim 45, “isolated” should be inserted before each instance of “cell population” and “of” should be inserted before each instance of “cells”.
Appropriate correction is required.
Claim Interpretation
Claims 36-43 and 45 recite limitations beginning with “preferably”. Preferred features are considered to be optional and are therefore not interpreted as necessarily limiting the scope of the claims.
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 36-45 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.
Regarding claims 36-43 and 45, the terms “preferably”, “e.g.”, and “for example” render the claims indefinite because it is unclear whether the limitation(s) following the terms are part of the claimed invention. See MPEP 2173.05(d). Dependent claim 44 is included in the rejection.
The limitation “expresses at least one Hypoblast marker at a low level” in claim 39 recites a relative term which renders the claim indefinite. The term “low level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 40-41 reference Table 1. Incorporation by reference to a specific figure or table 'is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.' Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). See MPEP 2173.05(s). It would be remedial to copy the table contents into the claims themselves.
Claim 41 recites the limitation “the high-deep in situ high-throughput chromatin conformation capture” in lines 12-13. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 36-39, 42, and 44-45 are rejected under 35 U.S.C. 102(a)(a) as being anticipated by Choi et al. (Stem Cell Reports, 2019).
Regarding claims 36-39, 42, and 44: Choi et al. teach chemically defined media for maintain pluripotency in pig ESCs (See Abstract). Blastocysts were seeded on feeder cells, and the ESC colonies were subcultured (See page 231, col. 1, full ¶1-2). The ESCs were stably maintained in culture for over 50 passages (which reads on “capable of stable passage for at least 30 times, at least 40 times, at least 50 times”) (See page 224, col. 1, ¶2). Pluripotency markers OCT4 (which reads on “POU5F1”), NANOG (which reads on “Epiblast marker”), SOX2, SSEA1, SSEA4, TRA-1-81, and TRA-1-60 were expressed by the cells (See fig. 2). The cells were capable of forming embryoid bodies and differentiating into cardiac muscle cells, pancreatic progenitors, and neural lineage cells (which reads on “has the capacity to differentiate into a cell of any one of endoderm, ectoderm, and mesoblast”) (See page 231, col. 1, full ¶3 and col. 2, ¶1). Undifferentiated cells exhibited little to no expression of SOX17 and GATA4 (which reads on “does not express or expresses at least one Hypoblast marker at a low level”) (See fig. 3A). Transcriptome analysis showed that the ESCs had the greatest similarity to epiblast cells (which reads on “having a pluripotency of pig pre-gastrulation Epiblast cells”) (See page 225, col. 2, ¶1 and page 228, col. 2, full ¶1).
Regarding claim 45: Following the discussion of claims 36-39 and 44, Choi et al. teach that the pig ESCs exhibited extensive staining for the pluripotency markers OCT4, SOX2, NANOG, SSEA1, and TRA-1-60, with significant overlap observed with the nuclear marker (which reads on “at least 50%... cells in the cell population are the pluripotent stem cells”) (See fig. 2C).
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.
Claims 36-38 and 42-45 are rejected under 35 U.S.C. 103 as being unpatentable over Alberio et al. (Stem Cells and Development, 2010), of record.
Regarding claims 36-38, 42-45: Alberio et al. teach the culture of pig epiblast stem cell lines from late ICM-Pre-steak i/ii epiblasts (which reads on “isolated pluripotent stem cell, having a pluripotency of pig pre-gastrulation Epiblast cells” and “derived from pre-gastrulation Epiblast of a pig embryo”) (See Abstract and page 1628, col. 1, full ¶1). The cells expressed the pluripotency markers OCT4 (which reads on “POU5F1”), SOX2, NANOG (which reads on “Epiblast markers”), NODAL (which reads on “Epiblast markers”), and SSEA1 (See fig. 2B-D). The cells exhibited extensive staining for OCT4 and NANOG (which reads on “at least 50%... cells in the cell population are the pluripotent stem cells”) and differentiation potential to ectoderm, mesoderm, and endoderm (See fig. 2C and 4).
Alberio et al. teach stable passage of the pig epiblast cells through 22 passages and do not expressly teach passage of the cells 30 or more times. However, Alberio et al. demonstrate that the cells stably express the pluripotency markers OCT4, SOX2, NANOG, and NODAL from passage 5 through passage 22 (See fig. 2D). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the culture method of Alberio et al. to comprise additional passages, thereby yielding a porcine epiblast cell capable of at least 30 passages. One would have been motivated to make this modification because the stable expression of pluripotency markers through 22 passages reasonably suggests to one of ordinary skill in the art that further passaging of the cells would be feasible. Such a modification could be readily made to the method of Alberio et al.
Allowable Subject Matter
Claims 40-41 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The prior art does not teach or suggest an isolated pluripotent stem cell having porcine pre-gastrulation epiblast pluripotency that is capable of at least 30 stable passages, wherein expression of one of more enumerated gene is increased at least two-fold relative to expression in a hESC or wherein at least one enumerated gene exhibits covariation between regulatory potential score and expression relative to a porcine embryonic fibroblast.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
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