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, 4, 8, 10, 14, 15, 17, 19, 21, 23, 28, 32, 33, 40, 44, 48, 49, 52, 54 and 67 are pending in this application.
Election/Restrictions
Applicant’s election of Group I (Claims 1, 4, 8, 10, 14, 15, 17, 19, 21, 23 and 28) in the reply filed on 03/26/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 32, 33, 40, 44, 48, 49, 52, 54 and 67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/26/2026.
Claims 1, 4, 8, 10, 14, 15, 17, 19, 21, 23 and 28 were examined on their merits.
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.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it is too short to describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The use of the terms FLUOVOLT™ and NANOSTRING™, 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 term. 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 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 14 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 term “resembles” is a relative term which renders the claim indefinite. The term 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. The disclosure does not define the degree or nature (e.g. physical? genetic?) of the “resemblance” such that the ordinary artisan could reasonably ascertain the metes and bounds of the claim. For purposes of examination, the Examiner has construed the claim as any immature cardiomyocyte resembling a fetal cardiomyocyte.
Claim Rejections - 35 USC § 102
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)(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, 8, 10, 14, 15, 17, 19, 23 and 28 are rejected under 35 U.S.C. § 102(a)(1) as anticipated by Lee et al. (WO 2020/247957 A2), cited in the IDS.
Lee et al. teaches a method of producing mature cardiomyocytes from immature
cardiomyocytes comprising contacting the immature cardiomyocytes with an mTOR
inhibitor (rapamycin, torin1, torin2) at varying concentrations and time points (pulse treatment) in 3D culture (Pg. 125, Lines 9-26 and Pg. 126, Lines 17-30);
wherein the immature cardiomyocytes are derived from an induced pluripotent stem cells (iPSCs) (Pg. 125, Lines 27-33 and Pg. 126, Lines 1-7), reading on Claims 1, 4, 8, 10 and 14.
With regard to Claim 15, the reference further teaches an embodiment wherein the immature cardiomyocytes are contacted with the mTOR inhibitor after the immature cardiomyocytes begin beating (Pg. 2, Lines 32-33 and Pg. 3, Lines 1-3).
With regard to Claim 17, the reference further teaches an embodiment wherein the immature cardiomyocyte exhibits increased expression of one or more genes of maturation as compared to an immature cardiomyocyte (Pg. 2, Lines 15-18).
With regard to Claim 19, the reference further teaches an embodiment wherein the immature cardiomyocyte exhibits increased expression of one or more sarcomeric proteins as compared to an immature cardiomyocyte (Pg. 2, Lines 18-20).
With regard to Claim 23, the reference further teaches an embodiment wherein the mature cardiomyocyte exhibits increased expression of REST and/or GATA4 as compared to an immature cardiomyocyte or exhibits a decreased beating rate as compared to an immature cardiomyocyte (Pg. 2, Lines 23-26);
wherein the mature cardiomyocyte exhibits a decreased beating rate as compared to an immature cardiomyocyte (Pg. 3, Lines 16-17);
wherein the resting membrane potential of the cardiomyocytes is within the range of greater than -70 mV (Pg. 52, Lines 5-9);
wherein the cardiomyocytes have an upstroke velocity of greater than 200 V/sec (Pg. 52, Lines 10-13).
With regard to Claim 28, the reference further teaches an embodiment wherein the mature cardiomyocyte is electrically, contractility and/or metabolically mature (Pg. 2, Lines 27-31).
Claims 1, 4, 10 and 14 are rejected under 35 U.S.C. § 103 as being unpatentable over Sacchetto et al. (05/11/2020).
Sacchetto et al. teaches a method of producing mature cardiomyocytes from immature cardiomyocytes comprising 3D-culturing hiPS-CMs (human induced pluripotent stem cell derived cardiomyocytes) in the absence of a cardiomyocyte maturation factor (Pg. 7, Paragraph 3 and Pg. 8, Table 2);
and separately teaches torin1, an mTOR inhibitor, and cardiomyocyte maturation factor, was shown to enhance hiPS-CMs maturation and promote a significant increased expression of mature cardiomyocyte markers in hiPS-CMs, as well as enhanced metabolic, contractile, and electrophysiological properties toward values observed in adult CMs (Pg. 7, Lines 5-9), reading on Claims 1, 4, 10 and 14.
Sacchetto et al. did not teach wherein immature cardiomyocytes were contacted with torin1 in 3D culture, as required by Claim 1.
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Sacchetto et al. of producing mature cardiomyocytes from immature cardiomyocytes using 3D culture to further treat the immature cardiomyocytes with torin1 because this would enhance cardiomyocyte maturation. Those of ordinary skill in the art would have been motivated to make this modification in order to obtain the desired mature cardiomyocytes. There would have been a reasonable expectation of success in making this modification because the reference teaches that torin1 treatment enhanced cardiomyocyte maturation.
Claims 1, 4, 8, 10, 14, 15, 17, 19, 21, 23 and 28 are rejected under 35 U.S.C. § 103 as being unpatentable over Sacchetto et al. (05/11/2020), as applied to Claims 1, 4, 10 and 14 above, and further in view of Garbern et al. (2019), cited in the IDS.
The teachings of Sacchetto et al. were discussed above.
Sacchetto et al. did not teach a method wherein the torin1 contacts the immature cardiomyocytes via pulse treatment, as required by Claim 8;
wherein the torin1 contacts the immature cardiomyocytes after they begin beating, as required by Claim 15,
wherein the mature cardiomyocytes have increased expression of one or more maturation genes as compared to an immature cardiomyocyte, as required by Claim 17;
wherein the mature cardiomyocytes have increased expression of one or more sarcomeric proteins as compared to an immature cardiomyocyte, as required by Claim 19;
wherein the mature cardiomyocytes have increased expression of one or more ion channel genes as compared to an immature cardiomyocyte, as required by Claim 21;
wherein the mature cardiomyocyte has increased expression of GATA4 as compared to an immature cardiomyocyte, as required by Claim 23;
or wherein the mature cardiomyocyte is electrically, contractility and metabolically mature, as required by Claim 28.
Garbern et al. teaches contacting beating immature cardiomyocytes derived from induced pluripotent stem cells with torin1 in a pulse treatment (Pgs. 287, Column 1, 3rd paragraph);
wherein the mature cardiomyocytes (torin1 treated) have increased expression of one or more maturation genes (TNNI3) as compared to an immature cardiomyocyte (control) (Pg. 290, Fig. 2A);
wherein the mature cardiomyocytes (torin 1 treated) have increased expression (e.g., contractility mature) of one or more sarcomeric proteins (TNNT2) as compared to an immature cardiomyocyte (control) (Pg. 290, Fig. 2A);
wherein the mature cardiomyocytes (torin 1 treated) have increased expression (e.g. electrically mature) of one or more ion channel genes (KCNJ2) as compared to an immature cardiomyocyte (control) (Pg. 293, Fig. 4A);
wherein the mature cardiomyocytes (torin 1 treated) have increased expression (e.g. metabolically mature) of one or more ion channel genes (PPARGC1) as compared to an immature cardiomyocyte (control) (Pg. 292, Fig. 3F);
and wherein the mature cardiomyocyte (torin1 treated) has increased expression of GATA4 as compared to an immature cardiomyocyte (control) (Pg. 294, Fig. 5A).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Sacchetto et al. of producing mature cardiomyocytes from immature cardiomyocytes using 3D culture to further treat the immature cardiomyocytes with torin1 using pulse treatment as taught by Garbern et al. because this would enhance cardiomyocyte maturation. Those of ordinary skill in the art would have been motivated to make this modification in order to obtain the desired mature cardiomyocytes. There would have been a reasonable expectation of success in making this modification because the reference teaches that torin1 treatment enhanced cardiomyocyte maturation.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 04/09/2026
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