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
This action is in response to the papers filed September 16, 2026.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/16/2026 has been entered.
Claim Amendments
Applicant’s amendment to the claims filed 09/16/2026 is acknowledged.
Claims 3, 5 and 21-32 have been cancelled.
Claim 1 is amended.
Claims 1-2, 4, 6-20 and 33 are pending and under examination.
Priority
The instant application 18/043,501 was filed on 02/28/2023. This application is a national stage of international application PCT/JP2021/042028 filed 11/16/2021, claiming priority based on Japanese patent application JP2020-190551 filed 11/16/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. A verified English-language translation of JP2020-190551 has been filed on 05/21/2026 in U.S. Application No. 18/043,501.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 06/16/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
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 1-2, 4, 6-20 and 33 are rejected under 35 U.S.C. 103 as being unpatentable US 2019/0269739 A1 to Brodie et al.; in view of WO 2017/204231 A1 to Nagamura et al.
WO 2017/204231 A1 to Nagamura et al. was published in a non-English language. This rejection relies on a machine translation of the publication generated by Google Patents. A paper copy of said translation has been provided with this action.
This rejection is newly applied, necessitated by amendment.
Brodie provides pharmaceutical compositions comprising a mesenchymal stromal cell (MSC) population, extracellular vesicles secreted therefrom, and a combination thereof, and methods of use thereof in treatment of a disease or disorder. See, Abstract.
The method of treating a disease or condition in a subject in need thereof comprises a step of administering the MSC population to the subject. See, e.g., par. 74, 97, 270.
The MSCs are umbilical cord-derived MSCs (UC-MSCs). See, e.g., par. 23. 53, 59, 86.
The disease or disorder is a muscular disease or disorder, including muscle aging or sarcopenia. See, e.g., par. 39, 43, 68, 97, 210, 212, 348-353.
Accordingly, Brodie is found to teach or fairly suggest a method for suppressing age-related muscle mass loss in a subject in need thereof comprising administering a cell preparation comprising umbilical cord-derived cells to the subject, as claimed in claim 1.
Brodie does not teach or fairly suggest obtaining umbilical cord-derived cells by cutting an umbilical cord tissue and culturing the cut umbilical cord tissue in a culture medium comprising a human mesenchymal stem cell basal medium and an animal-free additive, wherein the umbilical cord tissue comprises amnion, blood vessels, perivascular tissue, and Wharton jelly, as instantly claimed in claim 1.
Nagamura is relevant prior art for disclosing a process of obtaining a cell preparation comprising umbilical cord-derived cells, wherein the cell population is prepared using the umbilical cord as a raw material. In particular, the preparation method comprises a step of cutting the umbilical cord and culturing the cut umbilical cord. The cut umbilical cord tissue contains amnion membrane, blood vessels, perivascular tissue and Wharton jelly. The cut umbilical cord tissue is cultured in a culture solution suitable for umbilical cord-derived cells comprising a basal medium, such as mesenchymal stem cell growth medium, and an additive, such as a serum replacement or human serum. See, Abstract and pages 2-4 of the provided translation.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Brodie by obtaining umbilical cord-derived cells by cutting an umbilical cord tissue and culturing the cut umbilical cord tissue in a culture medium comprising a human mesenchymal stem cell basal medium and an animal-free additive, wherein the umbilical cord tissue comprises amnion, blood vessels, perivascular tissue and Wharton jelly, in view of Nagamura, with a reasonable expectation of success because such a preparation method would have been suitable for obtaining the desired umbilical cord-derived cells, and the use of animal-free components minimizes contaminants, reducing the risk of immune rejection.
Claim 1 further recites the umbilical cord-derived cell is positive for CD105, CD73, CD90, CD44, HLA-class I, HLA-G5 and PD-L2, and negative for CD45, CD34, CD11b, CD19 and HLA-Class II. Brodie teaches the MSCs express CD105, CD73, CD90, CD44, HLA-class I (HLA-A,B,C) and PD-L2 (CD273), and negative for CD45, CD34, CD11b, CD19 and HLA-Class II. See, e.g., par. 52, 321-322. Nagamura teaches the umbilical cord-derived cells are positive for CD105, CD73, CD90, CD44, HLA-class I, HLA-G5 and PD-L2, and negative for CD45, CD34, CD11b, CD19 and HLA-Class II. See, pages 2-3 of the provided translation. Accordingly, the cited prior art teaches that the umbilical cord-derived cell expresses or does not express the surface markers recited in claim 1.
For these reasons, claim 1 would have been prima facie obvious over the prior art.
Regarding dependent claim 2, Brodie teaches that the umbilical cord-derived cell is an umbilical cord-derived mesenchymal cell. See, e.g., par. 23. 53, 59, 86.
Regarding dependent claim 6, Brodie teaches administration of 1 x 106 cells to mice. See, par. 310, 357-359.
Regarding dependent claim 7, Brodie teaches the composition may further contain extracellular vesicles secreted from the UC-MSCs and/or conditioned media from the UC-MSCs. See, e.g., Abstract; par. 86-96.
Regarding dependent claim 33, Nagamura teaches that the preparation method further comprises passaging proliferating cells obtained from culturing the cut umbilical cord tissue. See, pages 3-4 of the provided translation.
Regarding dependent claims 4, 8-20, the claims further recite that the umbilical cord-derived cell, under an inflammatory condition, induces expression of a gene or a protein or both of at least one protein selected from the group consisting of IDO and PD-LI, or induces secretion of PGE2, or induces both the expression and the secretion, in the subject (claim 4); the cell preparation improves a mitochondrial function in a muscle tissue of the subject (claim 8); the cell preparation increases a number of mitochondria in a muscle tissue of the subject (claim 9); the cell preparation induces expression of a mitochondrial function-improving gene in a muscle tissue of the subject (claim 10), wherein the mitochondrial function-improving gene is at least one gene selected from the group consisting a PGC1-α gene, a COX4 gene, and a GLUT4 gene (claim 11); the cell preparation suppresses apoptosis of muscle cells of the subject (claim 12); the cell preparation exhibits an anti-inflammatory effect in a muscle tissue of the subject (claim 13); the cell preparation suppresses expression of at least one gene selected from the group consisting of an inflammatory cytokine gene and a chemokine gene, in a muscle tissue of the subject (claim 14), wherein the inflammatory cytokine gene is a TNF-α gene (claim 15), wherein the chemokine gene is a MCP-1 gene (claim 16); the cell preparation promotes proliferation of muscle cells of the subject (claim 17); the cell preparation induces expression of a muscle cell proliferation-promoting gene in the subject (claim 18), wherein the muscle cell proliferation-promoting gene is a TGF-β1 gene (claim 19); and the cell preparation exhibits a muscle tissue-repairing effect in the subject (claim 20).
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). See, MPEP 2112.
In this case, the above limitations of claims 4, 8-20 describe the intended results and/or functional properties of performing the process steps (manipulative actions) positively recited in claim 1. A recitation of an intended result or functional property of the claimed process must result in a manipulative difference between the claimed process and the cited prior art in order to patentably distinguish the claimed process from the cited prior art. If the prior art process is capable of performing the intended result, or if the functional property naturally flows from the prior art process, then the prior art reads on the intended result or functional property recitation. There is no requirement that the cited prior art expressly teach or suggest the intended result or functional property recitation, but only that the subject matter is, in fact, present in the cited prior art. As outlined above, the manipulative actions positively recited by the claims would have been prima facie obvious over the cited prior art. In particular, Brodie teaches the administration of umbilical cord-derived cells to a subject in need of suppression of muscle mass loss, and Nagamura teaches preparing the umbilical cord-derived cells by culturing cut umbilical cord tissue comprising comprises amnion, blood vessels, perivascular tissue and Wharton jelly, as claimed in claim 1. Therefore, the intended result and/or functional property limitations would have naturally flowed from performing the process steps taught by cited references.
In addition, Brodie discloses similar results and/or functional properties as those claimed in claims 4, 8-20, including increased mitochondria transfer, suppression of inflammation, reduced expression of cytokines and TNF-alpha, and muscle regeneration. See par. 223, 348-353. Moreover, Nagamura discloses expression of IDO, PGE2 and PD-L1 is induced under conditions of inflammation. See, page 2 of the provided translation.
For these reasons, absent evidence to the contrary, the intended results and/or functional properties of dependent claims 4, 8-20 are not found to patentably distinguish the claimed invention from the cited references.
Response to arguments:
Applicant’s remarks filed 09/16/2026 have been carefully considered, but are not found persuasive for the following reasons:
Applicant argues that there is no reason to combine Brodie and Nagamura to arrive at te claimed invention because (i) Nagamura relates to umbilical cord-derived cells for treating brain disorders and does not suggest sarcopenia or muscle aging, and (ii) Brodie does not teach or suggest any need to improve its cells or cell production method. See, pages 5-6 of the reply.
The arguments against the references individually are not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, the ordinary skilled artisan knew from Brodie that umbilical cord-derived cells possessed utility in treating muscle dystrophies or disorders, including muscle aging or sarcopenia. Nagamura is provided for teaching a means of obtaining the umbilical cord-derived cells taught by Brodie.
Applicant further argues that “serum replacement” or “serum substitute,” as found in the machine-generated translations of Nagamura, are not necessarily free of animal-derived materials, and the disclosed species – albumin, transferrin, fatty acids, insulin, sodium selenate, cholesterol, collagen precursors, trace elements, 2-mercaptoethanol and 3’-thiol glycerol – are generally found in animals. Therefore, Nagamura provides no specific reason or suggestion to select an “animal-free additive” as claimed.
The argument is not persuasive. "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). See MPEP 2144.01. In this case, prior to the effective filing date of the instantly claimed invention, serum additives were known to be a chemically-undefined cell culture additives comprising xenogenic or allogeneic constituents, and Nagamura expressly teaches replacing or substituting the serum additive in the cell culture. Although a number of the disclosed species may be found in animals and isolated therefrom, including albumin, transferrin and insulin, such species are also recombinantly produced from cells cultured in vitro by routine and conventional means. Other species, including 2-mercaptoethanol and 3’-thiol glycerol, are not typically isolated from animals but rather conventionally made by chemical synthesis. Perhaps most importantly, however, is the finding that Nagamaru expressly describes the species as replacements or substitutes for serum, and therefore Nagamura reasonably conveys that the disclosed species are not derived from their animal source in serum.
In addition, the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992); see also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); Ex parte Clapp, 227 USPQ 972 (Bd. Pat. App. & Inter. 1985) (examiner must present convincing line of reasoning supporting rejection); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See, MPEP 2144. In this case, the rejection provides a clear motivation to avoid animal-derived component in the cell culture, i.e., to minimize contaminants and reduce the risk of immune rejection, which was generally known in the field of cell-based therapy prior to the effective filing date of the instantly claimed invention.
Applicant further argues that the ordinary skilled artisan, when considering the cited references, would not have expected umbilical-cord derived cells would provide a therapeutic effect in treating sarcopenia or muscle aging, as claimed. Applicant argues that none of the working examples in Brodie relate to treating sarcopenia or age-related muscle mass loss, but rather the working examples relate to Duchenne muscular dystrophy (DMD) and drug-induced acute muscle injury, which differ significantly in etiology and pathogenesis.
The argument has been carefully considered but found unpersuasive based on the preponderance of evidence, as outlined below:
As an initial matter, although Brodie provides no working examples for treating sarcopenia or muscle aging, Brodie does nonetheless teach treating sarcopenia or muscle aging within the specification. Further, while significant etiological and pathogenetic exist, sarcopenia or age-related muscle mass loss are broadly related to muscular dystrophies or injuries as being associated with muscle weakness and/or loss of muscle mass.
The inquiry whether treatment of sarcopenia or age-related muscle mass loss was enabled in the prior art, or that one of ordinary skill in the art would have had a reasonable expectation of success in doing so, must not only consider the references cited under 35 U.S.C. 102 or 103 but rather take into account the teachings of the prior art, as a whole, at the time of filing. In this case, prior to the effective filing date of the instantly claimed invention, US 2020/0188440 A1 to Brodie et al. (published: 18 Jun 2020), which shares inventorship with cited US 2019/0269739 A1 to Brodie et al., provides a working example (Example 9, paragraphs 198-201) using umbilical cord-derived mesenchymal stem cells (UC-MSCs) to treat sarcopenia, and Wang et al. (2018) “Human umbilical cord Wharton’s jelly derived mesenchymal stromal cells may attenuate sarcopenia in aged mice induced by hindlimb suspension” Medical science monitor: international medical journal of experimental and clinical research, 24, 9272-9281, describes using human umbilical cord Wharton’s Jelly derived mesenchymal stromal cells (hWJ-MSCs) to treat sarcopenia in model mice, resulting in significantly increased whole body muscle strength and endurance, gastrocnemius muscle mass and myofiber cross-sectional area (CSA) compared to controls. Accordingly, although cited Brodie (US 2019/0269739 A1) teaches treatment of sarcopenia or age-related muscle mass loss but does not reduce to practice said treatment, one of ordinary skill in the art would had available similar prior art disclosures with reductions to practices, at the time of filing, when considering the teachings of cited Brodie.
For these reasons, based on the evidence of record, the argument is not found persuasive.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
