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 .
Status of the Claims
Claims 1-2, 4-6, 10-13, 15, 19-21, 31, 32, and 35-39 are pending.
Claims 31-32, and 35-39 are withdrawn.
Applicant’s election without traverse of group I claims 1-2, 4-6, 10-13, 15, 19-21, 31, 32, and 35-39 in the reply filed on 12/10/2025 is acknowledged. Claims 31-32, and 35-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Information Disclosure Statement
The listing of references in 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, they have not been considered.
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.
(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.
Grijalva
Claims 1, 4, 6, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Grijalva, Sandra I., et al. "Engineered cardiac pacemaker nodes created by TBX18 gene transfer overcome source–sink mismatch." Advanced Science 6.22 (2019): 1901099.
PNG
media_image1.png
265
557
media_image1.png
Greyscale
Regarding claim 1, Grijalva engineered TBX18‐induced pacemaker spheroids and patterned the spheroids to model the SAN's ability to pace‐and‐drive the neighboring myocardium. (Grijalva, Conclusion, Figure 5a-b appears below).
First Grijalva teaches the engineering of TBX18 spheroids from Neonatal rat ventricular myocytes (NRVM) which they found to demonstrate pacemaker activity. (Grijalva, Section 2.3). To test if TBX18 spheroids were able to pace‐and‐drive the neighboring myocardium, Grijalva patterned sphTBX18 within a rectangular shape to serve as an electrical ‘source' and juxtaposed monolayers of NRVMs as an electrical “sink” in fixed dimensions. (Grijalva, Fig. 5a).
Grijalva teaches an engineered cardiac tissue structure comprising a support having a first side (the mold). (Figure 5b, ii or iii).
Grijalva teaches a first engineered cardiac tissue layer/area/region disposed at the first side of the support (The monolayer NVRM seeded into the larger sink area in the mold).
PNG
media_image2.png
617
872
media_image2.png
Greyscale
Grijalva’s mold includes a narrower section (Section 2 and 3), (See attached drawing made by the examiner for clarity). The TBX18 pacemaker cells are disposed into the narrow end of the mold (Section 2), and the third region forms a conduction pathway for the propagation of action potentials between the second region (Section 2 of drawing) and the first region (section 1 of drawing). Grijalva in Figure 5 section c shows that the cells in the end, of the narrow end propagate a conduction pathway through to the attached larger monolayer of cells (pictured is a calcium activation map of conduction propagations from Grijalva’s Fig. 5).
Regarding the limitation that the second region forms a geometrically insulated cardiac tissue node, the specification defines G-Node as another term for geometrically insulated node. (Spec. [0068]). The specification defines G-node as “an isolated cluster of cells connected through a single conducting exit pathway.” (Spec. [0171]) So, in this case, Grijalva’s clump of engineered pacemaker cells placed into the narrow end of the mold reads on a geometrically insulated cardiac tissue node, because they are connected through a single conducting exit pathway (section 2) to the cardiomyocyte monolayer/sink (Section 1).
Grijalva anticipates claim 1.
Regarding claim 4, Grijalva’s engineered tissue structure has a perimeter and doesn’t contact any other cardiac cells beyond the perimeter. (Grijalva, Fig. 5a-b).
Regarding claim 6, Grijalva’s engineered tissue structure appears to be sized and shaped for spontaneous contraction of the first region (sink) to initiate/be triggered in the second region (smaller region with engineered pacemaker cells) more often than in the first region. Grijalva doesn’t mention the shape’s influence on this outcome specifically, but they analyzed the frequency of source‐to‐sink propagation in a quantitative manner. They found that when the source has limited contact with the sink, but not embedded by the sink, (design (ii)), majority of the beats were initiated from spheroids in sphTBX18 cocultures. (Grijalva Section 2.5). So, Grijalva’s engineered tissue is shaped in such a way to permit the spontaneous contractions as claimed.
Regarding claim 10, Grijalva’s second region comprised TBX18‐induced pacemaker cell spheroids that acted as a cardiac pacemaker for the engineered cardiac tissue structure. (Grijalva, Fig. 5).
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.
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.
Grijalva
Claims 1, 2, 4-6, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over:
Grijalva, Sandra I., et al. "Engineered cardiac pacemaker nodes created by TBX18 gene transfer overcome source–sink mismatch." Advanced Science 6.22 (2019): 1901099.
Claims 1, 4, 6, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grijalva.
Regarding claim 2, Grijalva’s engineered tissue structure lacks the claimed narrower second area, which might be described as a “neck” between the larger NRVM sink and the smaller area containing the engineered cardiomyocyte pacemaker cells.
However, generally speaking, changes in shape without some evidence that the specific configuration is significant to the invention are not patentable. In reDailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966) (The court held that the configuration of the claimed disposable plastic nursing container was a matter of choice which a person of ordinary skill in the art would have found obvious absent persuasive evidence that the particular configuration of the claimed container was significant.).
Regarding claim 5, Grijalva’s engineered tissue structure has corners, and at least in some of the images appear to be rounded somewhat, but it is not clear if that is just the cells themselves just not reaching the edges of the mold, or the mold itself. (Grijalva, Fig. 5a-b). However, this “rounded” limitation is just directed to a change in shape, and generally speaking changes in shape without some evidence that the specific configuration is significant to the invention are not patentable. In reDailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966) (The court held that the configuration of the claimed disposable plastic nursing container was a matter of choice which a person of ordinary skill in the art would have found obvious absent persuasive evidence that the particular configuration of the claimed container was significant.).
Allowable Subject Matter
Claims 19-21 are allowed.
Claims 11-13, and 15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art, Grijalva, fails to suggest the double-sided cardiac tissue structure encompassed by claim 11 and 19, and especially let alone the swimming structure of claim 15. The prior art, Grijalva included, seems more concerned with describing models to study signal propagation among cardiomyocytes, whereas this claimed invention appears to be a totally novel application of a double-sided cardiomyocyte tissue structure.
Conclusion
Claims 1, 2, 4-6, and 10 are rejected.
Claims 11-13 and 15 are objected to.
Claims 19-21 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS RUSSE AMICK whose telephone number is (571)272-5474. The examiner can normally be reached 7:30-5 M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/THOMAS R. AMICK/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights