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 .
Response to Amendment
Applicant’s amendment filed 03/04/2026 is acknowledged. Claims 1, 7, 9 and 12 are amended. Claims 1, 4, 5, 7, 9, 10, 12, 16, 21 and 29 are pending and under examination.
Rejections Withdrawn
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112(a)
The rejection of claims 1, 5, 7, 9, 10, 12, 16, 21 and 29 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in response to Applicant’s amendment. Specifically, the claims now clearly require that both the MYDGF and the fragment/variant share 97% sequence identity to SEQ ID NO: 1. Further, claims 7, 10 and 12 have been amended to delete “preventing”.
Rejections Maintained
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
Claim Rejections - 35 USC § 103
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.
The rejection of claims 1, 4, 5, 7, 9, 10, 16 and 21 under 35 U.S.C. 103 as being unpatentable over Korf-Klingebiel et al. (Nat Med. 2015 Feb;21(2):140-9—on IDS filed 07/19/2022) in view of Talman (Cell Tissue Res (2016) 365:563–581) and Linck et al. (Cardiovascular Research 31 (1996) 625-632) is maintained for reasons of record and the following.
Response to Arguments
Applicant argues at p. 5 of the Remarks filed 03/04/2026 that “scarring effects after myocardial infarction [MI] and interstitial fibrosis in chronic heart failure are two distinct phenomena”. Applicant’s assert further that while Korf-Klingebiel et al. teach MYDGF limits initial damage and improves wound healing, resulting in smaller scar following MI, the authors are silent with respect to “any direct antifibrotic effects of MYDGF”.
This argument has been fully considered, but is not found persuasive. First, none of the claims require treatment of interstitial fibrosis in chronic heart failure. Claim 1 and its dependents recite only treating or reducing fibrosis. Claim 7 and its dependents recite “treating or reducing fibrosis, heart failure, and/or hypertrophy”, and therefore read on treating only fibrosis in the alternative. While Korf-Klingebiel and colleagues do not teach fibrosis, per se, the supporting reference by Talman teaches that the scar formation that occurs after MI is fibrosis (see p. 563, right column, 2nd paragraph):
The fibrotic response after an MI can be classified into two types of fibrosis, namely replacement and reactive fibrosis, both of which are mediated by fibroblasts and myofibroblasts. Replacement fibrosis, i.e. scar formation, is a pivotal process to prevent the rupturing of the ventricular wall after an ischemic insult. However, the increased mechanical stress post-MI, together with hormonal and paracrine media tors, also induces the expansion of connective tissue in areas remote to the infarction. This reactive fibrosis in the infarct border zone and in the remote uninjured myocardium leads to altered chamber compliance and increased ventricular stiffness thereby compromising cardiac output. (Citations omitted by examiner).
Thus, the prior art teachings as a whole suggest that the methods taught by Korf-Klingebiel reduce “replacement fibrosis”, referred to therein as scarring. Further, for the record, the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983). See also MPEP 2112.
Applicant cites case law at the top of p. 6, to which the examiner takes no issue. Applicant also argues at pages 6-7 that the instant specification provides evidence of unexpected effects, citing to the examples in the specification. Applicant concludes that the applied prior art neither teaches nor suggests any direct antifibrotic effects of MYDGF on fibroblasts and an antifibrotic efficacy in heart failure. Applicant argues further that Talman’s teaching that scar formation is replacement fibrosis does not imply that any effect on scar formation or scar size inevitably impacts fibrosis and asserts that the skilled artisan would understand that the size of the scar depends on the size of the initially damaged myocardial area and on the quality of the subsequent healing process. Applicant concludes that the combination of references does not teach any direct antifibrotic effects of MYDGF on fibroblasts.
These arguments have been fully considered, but are not found persuasive. The MPEP 716.02(d) instructs that unexpected results must be commensurate in scope with the claimed invention. Regarding the cited examples, the claims are silent with respect to any effects on (1) collagen 1A1 and CTGF expression, (2) smooth muscle actin promoter activity, or (3) TGF-beta-induced gene expression changes observed in cultured neonatal rat ventricular fibroblasts. The claims are also silent with respect to any effects on inhibiting SMAD phosphorylation or migration of cultured in cultured human lung fibroblasts or in cultured mouse embryonic fibroblasts. Applicant argues that the applied prior art references are silent with respect to the effect on fibroblasts, however, the claims broadly claim treating or reducing fibrosis (claim 1) or fibrosis, heart failure, and/or hypertrophy (claim 7), therefore, the cardiac fibrosis resulting from myocardial infarction taught in the applied prior art is also encompassed by the claims. Further, Talman teaches “[t]he fibrotic response after an MI can be classified into two types of fibrosis, namely replacement and reactive fibrosis, both of which are mediated by fibroblasts and myofibroblasts”, therefore the applied prior art also teaches that fibrosis resulting from MI is mediated by fibroblasts.
New Rejection under 35 USC § 103
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Korf-Klingebiel et al., Talman and Linck et al. as applied to claims 1, 4, 5, 7, 9, 10, 16 and 21 above, and further in view of Szibor et al. (WO 2014/096437). Claim 12 is drawn to a method for treating or reducing fibrosis, heart failure, and/or hypertrophy comprising administering to a patient in need thereof a therapeutically effective amount of a host cell comprising the nucleic acid of claim 7. The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. The combined teachings of Korf-Klingebiel et al., Talman and Linck et al. and how they meet the limitations of claims 1, 4, 5, 7, 9, 10, 16 and 21 are outlined above in the preceding rejection and are hereby incorporated. See also pages 9-11 of the Office action mailed 12/16/2025, hereby incorporated. The second factor to consider is to ascertain the differences between the prior art and the instant claims. While Korf-Klingebiel et al. teach administering an Mydgf nucleic acid (i.e., gene therapy) to a mouse model for myocardial infarction, they do not explicitly teach administering a host cell comprising the nucleic acid of claim 7.
Szibor et al. teach methods in which host cells carrying polynucleotides are used to treat lung and heart damage (see abstract; paragraph bridging pages 22-23; top. of p. 24; p. 25, lines 21-36; paragraph bridging p. 27-28 and claims 4-11). It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the combined teachings of Korf-Klingebiel et al., Talman and Linck et al. by delivering the polynucleotide via the host cell, as taught by Szibor et al. because it represents an alternative method of gene therapy. The person of ordinary skill in the art would have been motivated to use host cells as a delivery vehicle for polynucleotides because they represent a simple substitution of one known method for another. The prior art taught that polynucleotides could also be delivered via a host cell (see cited portions of Szibor). The person having ordinary skill in the art would be choosing from a finite number of identified methods for administering polynucleotides. Furthermore, the person of ordinary skill in the art could have reasonably expected success because Szibor et al. teach that methods of engineering host cells for gene delivery were known in the art (see p. 22, lines 23-36).
Thus, the claims do not contribute anything non-obvious over the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The provisional rejection of claims 1, 4, 5, 16 and 21 on the ground of nonstatutory double patenting as being unpatentable over claims 42-47 of copending Application No. 18/871,433 in view of Linck et al. (Cardiovascular Research 31 (1996) 625-632) and Wollert (WO 2014/111458—of record) is maintained for reasons of record and the following.
No arguments were made with respect to the rejection; rather Applicants’ request deferral of this issue until other issues of patentability are resolved in their response filed 03/04/2026 is acknowledged. However, deferral of arguments is not proper; an argument after the claims have been found otherwise allowable that obviousness type double patenting does not exist will not be considered timely. Accordingly, the provisional rejection is maintained.
Claim Objections
Claim 29 is 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.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
