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
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.
Response to Amendments
Applicant’s amendments, corrected drawings and specification, and response filed Oct. 17, 2025 have been received and entered into the case.
Status of the Claims
Claims 1-5, 7-10, and 31 are currently pending.
Claims 1, 3, 5, and 7 are amended.
Claims 6 and 11-30 are cancelled.
Claim 31 is new.
Claims 1-5, 7-10, and 31 have been considered on the merits.
Drawing Objections
The drawing objections for illegible text are withdrawn due to amendment. The objections for the description of color for Fig. 7 and 22 are maintained, since the specification has not been amended to remove the description of color.
The disclosure is objected to because of the following informalities:
The drawings are objected to because of the following informalities: there is illegible text in Fig. 4, 7, 9, 11, 13, 25-26, 30, and 37; and there is description of color in the Specification for Fig. 7 in para. 0122 and for Fig. 22 in para. 0152 and the various colors cannot be distinguished from each other since the figures are in black and white.
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 Objections
Specification objections are withdrawn due to amendment.
Claim Rejections - 35 USC § 112
The claim rejections under 35 USC § 112, (b) or second paragraph (pre-AIA ), are withdrawn due to amendment. New claim rejections under 35 USC § 112, (b) or second paragraph (pre-AIA ) have been added to address the claim amendments.
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 1-5, 7-11 and 31 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.
In claim 1, line 8, the phrase “after a predetermined period of time”, renders the claim and its dependents indefinite, since it is unclear how the period of time is predetermined. The claim further defines that “the predetermined period of time is dependent on a length of the at least one CF bridge” in lines 12-13. It unclear whether the length is being used to predetermine the length of time. For the purposes of compact prosecution, “after a predetermined period of time” in the phrases will be interpreted to mean “after a
In claim 3, the phrase “wherein the MEA is measures a field potential of the at least two CM cell clusters”, renders the claim and its dependents indefinite, since it is unclear whether the MEA is meant to be capable of measuring a field potential or whether this is a step is intended to be a product-by-process type of limitation. For the purposes of compact prosecution, the phrase will be interpreted to mean “wherein the MEA is capable of measuring a field potential of the at least two CM cell clusters”, since the claim is to a composition and not a method.
In claim 6, line 8, the phrase “after a predetermined period of time”, renders the claim and its dependents indefinite, since it is unclear how the period of time is predetermined. The claim further defines that “the predetermined period of time is dependent on a length of the at least one CF bridge” in lines 12-13. It unclear whether the length is being used to predetermine the length of time. For the purposes of compact prosecution, “after a predetermined period of time” in the phrases will be interpreted to mean “after a
In claims 6 and 7, lines 1-2, the phrases:
“wherein a first of the at least two CM cell clusters oscillating at a first initial beating frequency and a second of the at least two CM cell clusters oscillating at a second initial beating frequency”,
“wherein after a predetermined period of time, the first of the at least two CM cell clusters and the second of the at least two CM cell clusters oscillate at a same synchronized beating frequency, the first and second beating frequencies being different than the synchronized beating frequency”, and
“wherein the predetermined period of time is dependent on a length of the at least on CF bridge”,
render the claims and their dependents indefinite, since it is unclear if these limitations are steps that must happen, meant to be characteristics of the cells or meant to be product by process type limitations. It is unclear it is meant to be a product by process type limitation. For the purposes of compact prosecution, the phrases will be interpreted to be product by process type limitations.
All other claims depend directly or indirectly from rejected claims and are, therefore, also rejected under USC 112 for the reasons set forth above.
In claim 1, line 8, the phrase “after a predetermined period of time”, renders the claim and its dependents indefinite, since it is unclear how the period of time is predetermined. The claim further defines that “the predetermined period of time is dependent on a length of the at least one CF bridge” in lines 12-13. It unclear whether the length is being used to predetermine the length of time. For the purposes of compact prosecution, “after a predetermined period of time” in the phrases will be interpreted to mean “after a .
Appropriate correction is required.
Claim Rejections - 35 USC § 102
The claim rejections under 35 USC § 102 are withdrawn due to amendment. New claim rejections under 35 USC § 102 have been added to address the claim amendments.
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 1, 4, 5, 7-10, and 31 are rejected under 35 U.S.C. 102(a) as being anticipated by Gaudesius et al. (Circulation Research, 2003) (ref. of record) as evidenced by Zorlutuna (US 2017/0069860 A1).
With respect to claims 1, 7, 9 and 10, Gaudesius teaches a heterocellular culture model which has impulse propagation where strands of cardiomyocytes are electrically coupled to fibroblasts and each other (a coupled bio-oscillating material) (abstract and pg. 424 para. 1). With respect to claims 1 and 7, Gaudesius teaches multiple strands of cardiomyocytes with cardiac fibroblasts filling in gaps between cardiomyocyte strands on an agar substrate (at least two cardiac (CM) muscle clusters and at least one cardiac fibroblast (CF) cell bridge on a substrate; and at least two biological oscillators, and at least one biological coupling element connecting the at least two biological oscillators) (Fig. 1 and Fig. 2A). With respect to claims 1 and 8, Gaudesius teaches that the fibroblasts of cardiac origin are capable of relaying electrical excitation between two separated strands of cardiomyocytes linked by the fibroblasts (the at least one CF bridge provides electrical conduction between the at least two CM cell clusters; and the at least two biologically oscillators are connected electrically, mechanically, and optically) (pg. 422 para. 1 and pg. 423 Col. 2 para. 2). With respect to claims 1 and 7, Gaudesius teaches that the linked cardiomyocyte stands have spontaneous contractions, synchronization and have impulse propagation along the strand (oscillate and synchronize at a unique phase ordering between the two CM cell clusters or two biological oscillators) (pg. 423 Col. 2 para. 2-3).
With respect to claims 1 and 7, Gaudesius teaches the cardiomyocyte stands initially have contractile activity that is different and which eventually synchronize (oscillate at frequencies different from the synchronized frequency) (pg. 423 Col. 2 para. 2). Gaudesius teaches that the frequency of spontaneous contractions varied among the strands and the functional linking of the strands by fibroblasts established synchronization (first of the at least two CM cell clusters oscillating at a first initial beating frequency and a second of the at least two CM cell clusters oscillating at a second initial beating frequency) (pg. 423 Col. 2 para. 2). With respect to claims 1, 7 and 31, Gaudesius teaches that the synchronization of the contractile activity between the linked cardiomyocyte strains occurred as soon as 8 hours after seeding of the fibroblasts in short to middle size inserts whereas it took up to 24 hours for synchronization the inserts were longer (the period of time is dependent on a length of the at least on CF bridge) (pg. 423 Col. 2 para. 2).
Although Gaudesius teaches the method by which the cardiomyocyte strands or clusters are produced as claims 1, 7 and 31 are being interpreted, these limitations are interpreted as product by process type limitations. It is noted that the patentability of a product does not depend on its method of production. If the claimed product is the same or obvious from a product in the prior art (i.e. the product disclosed in the cited reference), the claim is unpatentable even though the reference product was made by a different process. When the prior art discloses a product which reasonably appears to be identical with or slightly different than the claimed product-by-process, rejections under 35 U.S.C 102 and/or 35 U.S.C 103 are proper. (MPEP 2113)
With respect to claim 4, Gaudesius teaches the cardiac fibroblasts (CF bridge) delay the activation and the activation delay increases as the length of the fibroblast insert increases (the CF bridge is equivalent to a Resistor-Capacitor (RC) filter) (pg. 424 Col. 1 para. 2).
Although, Gaudesius is silent with respect to synchronized frequency that the cardiomyocyte strands synchronize at and does not teach that the CM cell clusters synchronize at a frequency in the range from 0.01 to 10 Hz as recited in claim 5, this would inherently have occurred or be present in the composition of Gaudesius, since Gaudesius teaches the same composition containing at least two cardiac muscle cell clusters and at least one cardiac fibroblast cell bridge (abstract, pg. 424 para. 1, Fig. 1 and Fig. 2A). Additionally, Zorlutuna reports cultured cardiomyocytes which beat at a rate of 0.5 to 1.5 Hz (0111).
Therefore, the reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
The claim rejections under 35 USC § 103 are withdrawn due to amendment. New claim rejections under 35 USC § 103 have been added to address the claim amendments.
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 1-5, 7-10 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Gaudesius et al. (Circulation Research, 2003) (ref. of record) as evidenced by Zorlutuna (US 2017/0069860 A1) in view of Zorlutuna (US 2017/0069860 A1).
With respect to claims 1, 7, 9 and 10, Gaudesius teaches a heterocellular culture model which has impulse propagation where strands of cardiomyocytes are electrically coupled to fibroblasts and each other (a coupled bio-oscillating material) (abstract and pg. 424 para. 1). With respect to claims 1 and 7, Gaudesius teaches multiple strands of cardiomyocytes with cardiac fibroblasts filling in gaps between cardiomyocyte strands on an agar substrate (at least two cardiac (CM) muscle clusters and at least one cardiac fibroblast (CF) cell bridge on a substrate; and at least two biological oscillators, and at least one biological coupling element connecting the at least two biological oscillators) (Fig. 1 and Fig. 2A). With respect to claims 1 and 8, Gaudesius teaches that the fibroblasts of cardiac origin are capable of relaying electrical excitation between two separated strands of cardiomyocytes linked by the fibroblasts (the at least one CF bridge provides electrical conduction between the at least two CM cell clusters; and the at least two biologically oscillators are connected electrically, mechanically, and optically) (pg. 422 para. 1 and pg. 423 Col. 2 para. 2). With respect to claims 1 and 7, Gaudesius teaches that the linked cardiomyocyte stands have spontaneous contractions, synchronization and have impulse propagation along the strand (oscillate and synchronize at a unique phase ordering between the two CM cell clusters or two biological oscillators) (pg. 423 Col. 2 para. 2-3).
With respect to claims 1 and 7, Gaudesius teaches the cardiomyocyte stands initially have contractile activity that is different and which eventually synchronize (oscillate at frequencies different from the synchronized frequency) (pg. 423 Col. 2 para. 2). Gaudesius teaches that the frequency of spontaneous contractions varied among the strands and the functional linking of the strands by fibroblasts established synchronization (first of the at least two CM cell clusters oscillating at a first initial beating frequency and a second of the at least two CM cell clusters oscillating at a second initial beating frequency) (pg. 423 Col. 2 para. 2). With respect to claims 1, 7 and 31, Gaudesius teaches that the synchronization of the contractile activity between the linked cardiomyocyte strains occurred as soon as 8 hours after seeding of the fibroblasts in short to middle size inserts whereas it took up to 24 hours for synchronization the inserts were longer (the period of time is dependent on a length of the at least on CF bridge) (pg. 423 Col. 2 para. 2).
Although Gaudesius teaches the method by which the cardiomyocyte strands or clusters are produced as claims 1, 7 and 31 are being interpreted, these limitations are interpreted as product by process type limitations. It is noted that the patentability of a product does not depend on its method of production. If the claimed product is the same or obvious from a product in the prior art (i.e. the product disclosed in the cited reference), the claim is unpatentable even though the reference product was made by a different process. When the prior art discloses a product which reasonably appears to be identical with or slightly different than the claimed product-by-process, rejections under 35 U.S.C 102 and/or 35 U.S.C 103 are proper. (MPEP 2113)
With respect to claim 4, Gaudesius teaches the cardiac fibroblasts (CF bridge) delay the activation and the activation delay increases as the length of the fibroblast insert increases (the CF bridge is equivalent to a Resistor-Capacitor (RC) filter) (pg. 424 Col. 1 para. 2).
Although, Gaudesius is silent with respect to synchronized frequency that the cardiomyocyte strands synchronize at and does not teach that the CM cell clusters synchronize at a frequency in the range from 0.01 to 10 Hz as recited in claim 5, this would inherently have occurred or be present in the composition of Gaudesius, since Gaudesius teaches the same composition containing at least two cardiac muscle cell clusters and at least one cardiac fibroblast cell bridge (abstract, pg. 424 para. 1, Fig. 1 and Fig. 2A). Additionally, Zorlutuna reports cultured cardiomyocytes which beat at a rate of 0.5 to 1.5 Hz (0111).
Gaudesius does not teach the coupled bio-oscillating material where the substrate is embedded with a microelectrode array (MEA) and where the MEA is configured to measure a field potential of the at least two CM cell clusters as recited in claims 2 and 3.
However, Zorlutuna teaches similar a coupled bio-oscillating material which is cell-based diode where the cells are cardiomyocytes that spontaneously beat (0004, 0008, 0058 and 0110-0111). Zorlutuna teaches the material containing a chain of cardiomyocytes or a patch of cardiomyocytes connected to a patch of cardiac fibroblasts (0100 and 0116). Zorlutuna teaches the coupled bio-oscillating material where the substrate is embedded with a microelectrode array (MEA) and where the MEA is configured to measure a the electrical response of the micropatterned cells (field potential of the at least two CM cell clusters) (0106). Zorlutuna further teaches the MEA allows for simultaneous stimulation and recording of electrical channels and is capable of assigning recording and stimulation functions to individual channels (0106).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the coupled bio-oscillating material of Gaudesius to include a MEA for the benefit of measuring the electrical response of the cells on the substrate as taught by Zorlutuna. It would have been obvious to one of ordinary skill in art to include other known electrical measuring devices such as the MEA taught by Zorlutuna in the coupled bio-oscillating material of Gaudesius for the purpose of recording the electrical activity of the cardiomyocytes. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to the coupled bio-oscillating material of Gaudesius, since Zorlutuna teaches a similar coupled bio-oscillating material with a MEA and Gaudesius teaches measuring the electrical activity of the material (pg. 423 Col. 1 para. 3 and Fig. 2).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Oct. 17, 2025 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 102 and § 103, Applicant argues that the new limitations of amended claims 1 and 7 are not taught by Gaudesius and/or Zorlutuna (Remarks pg. 10-11 bridging para. and pg. 12 para. 1 and 4). The Applicant’s amendments limiting claims 1 and 7 to include the new limitations of
“wherein a first of the at least two CM cell clusters oscillating at a first initial beating frequency and a second of the at least two CM cell clusters oscillating at a second initial beating frequency”;
“wherein after a predetermined period of time, the first of the at least two CM cell clusters and the second of the at least two CM cell clusters oscillate at a same synchronized beating frequency, the first and second beating frequencies being different than the synchronized beating frequency”; and
“wherein the predetermined period of time is dependent on a length of the at least on CF bridge”,
necessitated new rejections. Applicant’s arguments are drawn to Gaudesius and Zorlutuna failing to teach these new limitations. However, the new limitations are addressed in the new rejections.
Applicant argues that Gaudesius is silent with respect to synchronized frequences and that the synchronization of frequencies is not inherent to the coupled bio-oscillating material of Gaudesius and/or Zorlutuna (Remarks pg. 11 para. 2). However, this argument was not found to be persuasive, since as explained in the rejections, Gaudesius teaches synchronization of the cardiac muscle cell clusters.
Applicant argues that the initial frequencies of the clusters are different and over time reach the same frequency dependent on the length of the CF (cardiac fibroblast cell) bridge as shown in the specification in para. 0123 and that these limitations are not inherent to Gaudesius and/or Zorlutuna (Remarks pg. 11 para. 2). Applicant argues that Zorlutuna does not teach synchronization or an association between the timing of synchronization with CF length (Remarks pg. 11 para. 2). The Applicant’s amendments limiting claims 1 and 7 to include the new limitation of “wherein the predetermined period of time is dependent on a length of the at least on CF bridge”, necessitated new rejections. Applicant’s arguments are drawn to Gaudesius and Zorlutuna failing to teach these new limitations. However, the new limitations are addressed in the new rejections.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632