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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12, in the reply filed on 12/01/2025 is acknowledged.
Claims 13-20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/01/2056.
Claims 1-12 as filed on 12/01/2025 are under examination in the instant office action.
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 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 1-5 and 7-11 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Ravi et al (“Effect of bone marrow-derived extracellular matrix on cardiac function after ischemic injury”. Biomaterials. November 2012, 33 (1), pages 1-13).
The cited reference by Ravi teaches that administration of extra-cellular matrix (ECM) preparation, that is produced/made from small segments of decellularized bone marrow tissue, to a rat model of myocardial infraction reduced infarct area lowered macrophage, improved cardiac function, reduced fibrosis or collagen deposition (see abstract, see page 6, it. 3.4). Thus, the cited reference discloses a method for treating a disease heart and altering proteome (by reducing collagen protein deposition). In view of applicants’ definitions (par. 0071 on specification page 13) the ECM-containing microtissue refers to 3D compositions comprising cells and ECM. In the cited method the bone marrow small segments, as a starting material in the cited method, are 3D microtissue compositions comprising bone marrow cells and ECM. In the cited method the bone marrow segments were subjected to decellularization by treating with DNase, surfactant, buffer and mixing/vertexing to produce ECM slurry (page 3, item 2.1) as encompassed by the claims for decellularized ECM particles within the meaning of the claims and in view of specification (see par. 0091 on page 116 describing the same decellularization protocol). Therefore, the cited method comprises same step of contacting a diseased heart with the same therapeutic material such as ECM produced from decellularized bone marrow microtissues for altering proteome as encompassed by the claims 1 and 7.
As applied to claims 2-5 and 8-11, the cited method provides for the same effects as result of practicing the same administration method. Moreover, the cited reference by Ravi clearly recognizes the same effects including lowering macrophage infiltration (altering immune response), improving cardiac function (altering metabolism), reduced fibrosis and collagen deposition or restoring normal level of collagens (page 6, it 3.4) as well as mitigating effects of various growth factors including TGF beta (paragraph bridging pages 7-8).
Thus, the cited reference by Ravi is considered to anticipate the claimed invention.
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.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Ravi et al (“Effect of bone marrow-derived extracellular matrix on cardiac function after ischemic injury”. Biomaterials. November 2012, 33 (1), pages 1-13) in view of US 7,060,494 (Bhat).
The cited reference by Ravi is relied upon as explained above for disclosure of a method of treating a disease heart by administering extra-cellular matrix (ECM) preparation, that is produced/made from decellularized bone marrow tissue small segment microtissues, to a rat model of myocardial infraction.
Although the reference by Ravi is silent about producing/providing ECM from tissue segments or microtissue with mesenchymal stem cells, it is well known that mesenchymal stem cells are present in mammalian bone marrow (of Ravi) including human bone marrow (see abstract of US 7,060,494).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed that the bone marrow-derived ECM in the method of the cited Ravi is produced/made from tissues comprising mesenchymal stem cells that are present in bone marrow. It would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to provide ECM from human bone marrow tissue segments in the method of the cited Ravi because all mammalian bone marrow including rat, swine and human contain mesenchymal stem cells.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Assuncao et al (“Cell-derived extracellular matrix for tissue engineering and regenerative medicine”. Frontiers in Bioengineering and Biotechnology. Published 03 December 2020. Volume 8, article 602009, pages 1-10) in view of Geon Hiu Lee et al (IDS reference; Adv Healthc Mater, 2016, (1), 56-74).
The cited reference by Assuncao teaches that cell-derived extra-cellular matrices (CD-ECM) are increasingly used in therapeutic applications (see abstract) including treating and repairing cardiovascular tissues (page 6) including diseased heart (figure 2). The cell-derived ECM are decellularized to remove immunogenic components (see page 2, col. 1, par. 3, line 5; see page 2, col. 2, par. 4-5). The cell-derived ECM are produced by several methodologies including 3D cultures of spheroids or 3D microtissues (figure 1). The cited reference by Assuncao recognizes that culturing ECM-secreting cells in 3D format achieves mechano-physical re-engineering of ECM scaffolds with unique architecture (page 5, col. 1, par. 4). ). The cited reference by Assuncao acknowledges that application of cell-derived ECM improves cardiac remodeling (Page 6, par. 3). The cited reference by Assuncao also recognizes the use of mesenchymal stem cells (MSC) - derived ECM for recapitulation of stem cell niche sufficiently, for protection of cells from oxidative stress and for promoting cell proliferation and cell differentiation (page 3, col. 2, lines 1-3) in therapeutic applications for tissue repairs.
Thus, as a whole, the cited reference by Assuncao teaches and suggests a method of treating a diseased heart and improving cardiac function by contacting the diseased heart with the cell derived ECM (figure 2), wherein the cell-derived ECM is made from 3D microtissues (fig. 1) by decellularization to remove immunogenicity .
Although the cited reference by Assuncao recognizes the beneficial effects of mesenchymal stem cells (MSC) - derived ECM, the disclosure is silent about providing 3D cultures or 3D microtissues derived/made from MSC. However, the reference by Geon Hiu Lee teaches that 3D microtissues could be made from MSC (table 1) and that 3D microtissues made from MSC maintain their multipotency and enhanced differentiation compared with 2D monolayers (page 58, col. 1, lines 10-12 from bottom).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to practice a method of treating a diseased heart and improving cardiac function by contacting the diseased heart with ECM produced by decellularization of 3D microtissues as taught and suggested by Assuncao. One of skill in the art would have been motivated to provide ECM derived from cultured 3D microtissues that are derived/made from MSC (as taught by Geon H lee) for the expected benefit in enhancing stem cell niche and protecting from oxidative cells as recognized by the prior art (Assuncao).
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
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Vera Afremova
March 17, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653