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 1-20, of record 1/20/2023, are pending and subject to prosecution.
Priority
Acknowledgement is made of the applicant’s claim for benefit to provisional application 63/308161, filed 2/9/2022.
Specification
The use of the terms Essential 8, B-27, Euthasol, OEC, Visipaque, Runthrough, NOGA, MyoStar, SIGMAFAST, NanoZoomer, Alexa Fluor, and Stata, 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 it appears 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.
Claim Objections
Claim 5 is objected to because of the following informalities:
In line 1 of claim 5, “amiod3arone” should be replaced with “amiodarone”.
Appropriate correction is required.
Claim Interpretation
Claims 1 and 13 recite the limitation “in vitro-differentiated cardiomyocytes”. The cardiomyocytes are defined using product-by-process limitations. Product-by-process limitations are considered only in so far as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product as claimed is the same or obvious over a product of the prior art (i.e., is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113. In the instant application, because the claims do not distinguish the in vitro-differentiated cardiomyocytes structurally from cardiomyocytes generated by other methods, the cardiomyocytes are interpreted as comprising any cardiomyocytes.
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 1, 3, 5, 7-8, 13-14, 16-17, and 19-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kempf et al. (US 20220257665 A1).
Kempf et al. teach methods for treating heart failure using stem cell-derived cardiomyocytes exposed in vitro to anti-arrhythmic agents (See Abstract).
Regarding claims 1, 3, 5, 13-14, 16-17: Kempf et al. teach the culture of a stem cell-derived cardiomyocyte population in a medium comprising one or more anti-arrhythmic agents (See ¶0011, 0077, and 0248-0251). The anti-arrhythmic agent can be amiodarone (See ¶0079). In embodiments, Kempf et al teach the culture of stem cell-derived (which and “in vitro-differentiated”) cardiomyocytes with 1 µM, 10 µM, or 100 µM amiodarone (which is equivalent to 0.65 µg/ml, 6.5 µg/ml, and 65 µg/ml and reads on “0.3 to 10 µg/ml”), however, the concentration of the anti-arrhythmic agent can range between 1-100 nM or 0.1-100 µM (See ¶0068). The cardiomyocytes can be cultured with the anti-arrhythmic agent for less than 24 h or at least 24 h (which read on “0-24 hours”) (See ¶0067). The stem cells can be ESC or iPSCs (See ¶0055-0056). The cardiomyocytes can also be obtained from transdifferentiated somatic cells (which reads on “direct reprogramming of non-cardiomyocytes”) (See ¶0056). The cardiomyocyte population can be transplanted or engrafted into the heart of a subject (See ¶0057-0060, 0069, 0115). The anti-arrhythmic agent can be co-administered in vivo with the cardiomyocytes (See Abstract and ¶0062-0063).
Regarding claims 7-8 and 19-20: Following the discussion of claims 1, 3, 5, 13-14, and 16-17, Kempf et al. teach that the cardiomyocytes can be transplanted with a biomaterial such as a synthetic hydrogel or a biomaterial that comprises hyaluronic acid or collagen (which reads on “a scaffold” and “extracellular matrix composition”) (See ¶0017, 0052, and 0064).
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.
Claims 1, 3, 5-14, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kempf et al. (US 20220257665 A1).
The teachings of Kempf et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 18: Following the discussion of claims 1, 3, 5, 7-8, 13-14, 16-17, and 19-20, Kempf et al. teach a method for preparing cardiomyocytes for transplantation through contacting in vitro with an anti-arrhythmic agent such as amiodarone, but do not expressly teach an embodiment wherein the arrhythmia burden in a subject is reduced relative to administration of untreated cardiomyocytes.
However, Kempf et al. teach that exposure to amiodarone decreases the beat-to-beat variability of stem-cell derived cardiomyocytes in vitro compared to a control (See fig. 15). One of ordinary skill could therefore reasonably expect the treated cells to show a similar reduction in beat-to-beat variability and susceptibility to arrhythmia following engraftment.
Claims 1-3, 5-14, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kempf et al. (US 20220257665 A1) in view of Zhou et al. (US 20230137971 A1).
The teachings of Kempf et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claims 2, 6, and 9-12: Following the discussion of claims 1, 3, 5, 7-8, 13-14, and 16-20, Kempf et al. teach a method for preparing cardiomyocytes for transplantation through contacting in vitro with an anti-arrhythmic agent such as amiodarone at between 1-100 nM or 0.1-100 µM and for up to 24 h (See ¶0011, 0067-0068, 0077, 0079, and 0248-0251). Kempf et al. do not expressly teach contacting the cells with a cryopreservative.
Zhou et al. teach compositions comprising induced cardiomyocytes generated by the reprogramming of differentiated cells (See ¶0046 and 0050). The cardiomyocytes can be frozen in a cryopreservation medium, such as one comprising 10% DMSO, and stored in liquid nitrogen for later use (which reads on “in a concentration sufficient to protect viability of the cells upon freezing”) (See ¶0299). The cells can also comprise a composition along with a cryoprotectant agent such as glycerol, sucrose, dextrose, and trehalose (See ¶0297).
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 composition of Kempf et al. to comprise the addition of a cryopreservative, such as is taught by Zhou et al., for storing the cells. One would be motivated to make this modification because Zhou et al. teach that cardiomyocytes frozen in this manner can be stored and thawed for later use (See ¶0299). There would be a reasonable expectation of success in doing so because a cryopreservative could be readily added to the cells of Kempf et al. for freezing.
Claims 1, 3-5, 7-8, and 13-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kempf et al. (US 20220257665 A1) in view of Knollmann et al. (WO 2021163037 A1).
The teachings of Kempf et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 4: Following the discussion of claims 1, 3, 5, 7-8, 13-14, and 16-20, Kempf et al. teach the transplantation of in vitro-differentiated cardiomyocytes cultured with amiodarone but do not expressly teach the cells as autologous (See ¶0011, 0077, 0079, and 0248-0251).
Knollmann et al. teach the administration of in vitro-differentiated cardiomyocytes and anti-arrhythmic drugs (See Abstract). The cardiomyocytes can be obtained by the differentiation of iPSCs derived from autologous cells (which reads on “the iPS cells are derived from a subject who will receive the transplant composition”) for reducing transplantation risks (See ¶0007, 0029, and 00108).
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 method of Kempf et al. to comprise the use of cardiomyocytes produced from autologous cells, such as are taught by Knollmann et al. One would be motivated to make this modification because Knollmann et al. teach that the use of autologous cells reduces the risk of engraftment rejection or allergic responses (See ¶00108). There would be a reasonable expectation of in doing so because the cardiomyocytes of Kempf et al. could be readily generated from autologous iPSCs.
Regarding claim 15: Following the discussion of claims 1, 3, 5, 7-8, 13-14, and 16-20, Kempf et al. teach the transplantation of cardiomyocytes with anti-arrhythmic agents such as amiodarone, but do not expressly teach the administration of ivabradine (See ¶0011, 0077, 0079, and 0248-0251).
Knollmann et al. teach that amiodarone and ivabradine can be co-administered in order to reduce engraftment arrhythmia and tachycardia and improve survival following cardiomyocyte engraftment (See Abstract; ¶0004-0005 and 0069; and fig. 1-2, 16, and 22-23).
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 method of Kempf et al. to further comprise administration of ivabradine, as taught by Knollmann et al. One would be motivated to make this modification because Knollmann et al. teach that the combination of amiodarone and ivabradine improves survival, prevents tachycardia, and reduces arrhythmia in subjects receiving cardiac grafts (See ¶0069). There would be a reasonable expectation of success in making this modification because Knollmann et al. demonstrate that both drugs can be used to improve the outcomes of cardiomyocyte transplantation in an animal model of myocardial infarction (See fig. 1-2, 16, and 22-23).
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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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633