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 February 28, 2023.
Claim Amendments
Applicant’s amendment to the claims filed 02/28/2023 is acknowledged.
Claims 1-20 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. While a certified copy of the foreign patent application is provided with the instant application, a certified English translation of said foreign patent application has not been provided.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/28/2023, 07/28/2023, 01/09/2025 and 09/24/2025 have been considered.
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, or by applicant in an information disclosure statement (IDS), they have not been considered.
Specification & Sequence Compliance
The specification is objected to because the present application is not found to be in compliance with the sequence rules, as set forth in 37 CFR 1.52(e)(8), 77(b)(5) and 821(c). In particular, the specification is missing an incorporation by reference of the material in the ASCII plain text file submitted on 02/28/2025, i.e., the “Sequence Listing,” in a separate paragraph, identifying the name of the file, its date of creation, and its size in bytes.
Claim Interpretation
Paragraph 15 of the specification defines the term the term "umbilical cord" to mean a white tubular tissue that connects the fetus and the placenta and does not include the placenta and umbilical cord blood.
Claim Objections
Claims 4-5 are objected to because of the following informalities:
In claim 4, line 5, the term “PGE2” should be “PGE2.” See paragraph 19 of the specification.
In claim 5, line 4, the phrase “consisting amnion” should be “consisting of amnion.”
Appropriate action is required.
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.
Claims 1-20 are 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.
Claim 1 recites a step of “using a cell preparation for use in suppressing muscle mass loss against a subject.” The terms “using” and “against,” as claimed, are found to render the scope of the claims indefinite.
First, regarding the term “using,” it is unclear how the claimed cell preparation is “used” for suppressing muscle mass loss. For example, it is unclear if the cell preparation itself is administered to the subject, or if the cell preparation is cultured in vitro to produce exosomes or conditioned medium which are administered to the subject instead of the cell preparation, or if the cell preparation comprises stem cells which are differentiated into muscle progenitor cells prior to administration to the subject, or if the cell preparation is “used” in some other manner. Accordingly, he claim is indefinite because it merely recites using the claimed cell preparation without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986), which held "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" to be indefinite. See MPEP 2173.05(q).
Second, regarding the term “against,” it is unclear how suppressing muscle mass loss is “against” the subject. For example, the preamble of the claim (“[a] method for suppressing muscle mass loss in a subject”) suggests that the method is broadly directed to treating muscle mass loss in a subject. However, by reciting that the cell preparation is used “against” the subject, the body of the claim, at least appears to, broadly suggest that the cell preparation does not, in fact, suppress muscle mass loss, but rather permits or promotes muscle mass loss in the subject. That is, the term “against” suggests that “suppressing muscle mass loss” is in opposition to the “subject.” It would appear, then, to be more appropriate to recite suppressing muscle mass loss “for” or “in” the subject in order to be consistent with the therapeutic purpose of the preamble of the claim.
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 4 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.
Claim 4 recites “at least one protein selected from the group consisting of ... PGE2.” The term PGE2 is defined in the specification to mean prostaglandin E2. However, prostaglandin E2 (PGE2) is not a “protein,” as claimed. Rather, PGE2 is a lipid molecule. Accordingly, PGE2 cannot be selected from the Markush grouping of claim 4 because PGE2 is a lipid molecule and not a “protein,” as claimed. In addition, there is no “gene” that expresses PGE2, as claimed in claim 4. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 5 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.
Claim 5 recites the umbilical cord-derived cell is a cell prepared from umbilical cord tissue, comprising at least one material selected from the group consisting amnion, blood vessels, perivascular tissue, and Wharton jelly. The recitation is indefinite because the “amnion” is not part of the “umbilical cord tissue,” as claimed. See, e.g., Lindenmair et al. (2012) “Mesenchymal stem or stromal cells from amnion and umbilical cord tissue and their potential for clinical applications” Cells, 1(4), 1061-1088. Accordingly, “amnion” cannot be selected from the Markush grouping of claim 5 because the amnion is part of the umbilical cord tissue, as claimed. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 7 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.
Claim 7 recites “at least one cell selected from the group consisting of an extract of the umbilical cord-derived cell and a secretion of the umbilical cord-derived cell.” The recitation is indefinite because the claim recites selection of a “cell” but no member of the Markush grouping is a “cell,” as claimed. In particular, both “an extract of the umbilical cord-derived cell” and “a secretion of the umbilical cord-derived cell” are not “cells,” as claimed. Accordingly, no member of the Markush grouping can be “selected” because none are a “cell.” For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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.
(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 1-2, 4, 8-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huang et al. (13 Oct 2021) “Potential of human instantaneous zone-derived mesenchymal cells for the treatment of sarcopenia” Journal of Japanese Association on Sarcopenia and Frailty, Vol. 5, Suppl. 2021.10, p. 124, of record in IDS filed 02/28/2023.
The “Huang” disclosure was published in a non-English language. This rejection relies on the machine translation provided in applicant’s IDS filed 02/28/2023. See Citation #7.
Huang investigated the use of human umbilical cord-derived mesenchymal cells (UC-MSCs) to treat age-related sarcopenia. US-MSCs were injected systemically into model Senescence-Accelerated Mouse prone 10 (SAMP 10) mice. The results of the study indicate that MSC cell therapy is expected to be an effective treatment for sarcopenia. See entire disclosure.
Accordingly, Huang is found to teach a method of treating sarcopenia (i.e., age-related loss of muscle mass and strength) in a subject, said method comprising a step of administering a cell preparation comprising umbilical cord-derived mesenchymal cells (UC-MSCs) to the subject.
For these reasons, Huang anticipates claim 1.
Regarding dependent claim 2, Huang discloses that the umbilical cord-derived cell is an umbilical cord-derived mesenchymal cell (UC-MSC). See entire disclosure.
Regarding dependent claims 4, 8-20, the claims further recite that the umbilical cord-derived cell induces expression of a gene or a protein or both of at least one protein selected from the group consisting of IDO, PGE2, or PD-LI under an inflammatory condition (claim 4); the cell preparation exhibits an effect of improving a mitochondrial function in muscle tissue (claim 8); the cell preparation exhibits an effect of increasing the number of mitochondria in muscle tissue (claim 9); the cell preparation exhibits an effect of inducing expression of a mitochondrial function-improving gene in muscle tissue (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 exhibits an effect of suppressing apoptosis of muscle cells (claim 12); the cell preparation exhibits an anti-inflammatory effect in muscle tissue (claim 13); the cell preparation exhibits an effect of suppressing expression of at least one gene selected from the group consisting an inflammatory cytokine gene and a chemokine gene, in muscle tissue (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 exhibits an effect of promoting proliferation of muscle cells (claim 17); the cell preparation exhibits an effect of inducing expression of a muscle cell proliferation-promoting gene (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 (claim 20)
Claim scope is not limited by claim language that does not limit a claim to a particular structure. See MPEP 2111.04. In this case, the above limitations of claims 4, 8-20 describe the intended results and/or functional properties which naturally flow from performing the process steps positively recited in the method of claim 1, i.e., a step of using a cell preparation comprising umbilical cord-derived cells. The limitations of claims 4, 8-20 do not clearly limit the claims to a particular structure or manipulative action. A recitation of an intended result or functional property of the claimed invention must result in a structural or manipulative difference between the claimed invention and the cited prior art in order to patentably distinguish the claimed invention from the cited prior art. If the prior art structure is capable of performing the intended result, or if the functional property naturally flows from the cited prior art structure, then the cited prior art reads on the intended result or functional property limitation. There is no requirement that the cited prior art expressly teach or suggest such an intended result or functional property limitation. As outlined above, the structure and manipulative actions positively recited by claim 1 is taught by the cited prior art. In particular, a process of using a cell preparation comprising umbilical cord-derived cells for suppressing muscle mass loss in a subject, as claimed in claim 1, is taught by Huang, and therefore the intended results and/or functional properties recited by dependent claims 4, 8-20 would have naturally flowed from the process of the prior art.
In addition, Huang discloses similar results and/or functional properties as those claimed in claims 4, 8-20, including increased muscle weight and strength, increased mitochondria number, expression of PGC1-1a and COX4 mRNA, suppression of muscle apoptosis and inflammation, reduced expression of TNF-a and MCP-1 mRNA, muscle cell proliferation, and muscle tissue regeneration. See Results.
For these reasons, 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 prior art.
Claims 1-2, 4-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2019/0269739 A1 to Brodie et al.
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 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, such as muscular dystrophy or sarcopenia. See, e.g., par. 39, 68, 97, 210, 348-353.
Accordingly, Brodie is found to anticipate a method for suppressing muscle mass loss in a subject comprising using a cell preparation comprising umbilical cord-derived cells for use in suppressing muscle mass loss in a subject, as claimed in claim 1.
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 5, Brodie teaches the umbilical cord-derived cell is a cell prepared from umbilical cord tissue, comprising Wharton’s jelly (WJ). See, e.g., par. 4, 298.
Regarding dependent claim 6, Brodie teaches administration of 1 x 106 cells to mice (par. 310, 357-359).
Regarding dependent claim 7, Brodie teaches extracellular vesicles secreted from the UC-MSCs. See, e.g., Abstract; par. 86-96.
Regarding dependent claims 4, 8-20, the claims further recite that the umbilical cord-derived cell induces expression of a gene or a protein or both of at least one protein selected from the group consisting of IDO, PGE2, or PD-LI under an inflammatory condition (claim 4); the cell preparation exhibits an effect of improving a mitochondrial function in muscle tissue (claim 8); the cell preparation exhibits an effect of increasing the number of mitochondria in muscle tissue (claim 9); the cell preparation exhibits an effect of inducing expression of a mitochondrial function-improving gene in muscle tissue (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 exhibits an effect of suppressing apoptosis of muscle cells (claim 12); the cell preparation exhibits an anti-inflammatory effect in muscle tissue (claim 13); the cell preparation exhibits an effect of suppressing expression of at least one gene selected from the group consisting an inflammatory cytokine gene and a chemokine gene, in muscle tissue (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 exhibits an effect of promoting proliferation of muscle cells (claim 17); the cell preparation exhibits an effect of inducing expression of a muscle cell proliferation-promoting gene (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 (claim 20)
Claim scope is not limited by claim language that does not limit a claim to a particular structure. See MPEP 2111.04. In this case, the above limitations of claims 4, 8-20 describe the intended results and/or functional properties which naturally flow from performing the process steps positively recited in the method of claim 1, i.e., a step of using a cell preparation comprising umbilical cord-derived cells. The limitations of claims 4, 8-20 do not clearly limit the claims to a particular structure or manipulative action. A recitation of an intended result or functional property of the claimed invention must result in a structural or manipulative difference between the claimed invention and the cited prior art in order to patentably distinguish the claimed invention from the cited prior art. If the prior art structure is capable of performing the intended result, or if the functional property naturally flows from the cited prior art structure, then the cited prior art reads on the intended result or functional property limitation. There is no requirement that the cited prior art expressly teach or suggest such an intended result or functional property limitation. As outlined above, the structure and manipulative actions positively recited by claim 1 is taught by the cited prior art. In particular, a process of using a cell preparation comprising umbilical cord-derived cells for suppressing muscle mass loss in a subject, as claimed in claim 1, is taught by Brodie, and therefore the intended results and/or functional properties recited by dependent claims 4, 8-20 would have naturally flowed from the process of the prior art.
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.
For these reasons, 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 prior art.
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0269739 A1 to Brodie et al., as applied to claims 1-2, 4-20 above; in view of Ding et al. (2016) “Characterization of HLA-G and related immunosuppressive effects in human umbilical cord stroma-derived stem cells” Cell transplantation, 25(2), 217-228.
Regarding dependent claim 3, the claim 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.
However, Brodie is silent with regards to HLA-G5 expression.
Prior to the effective filing date of the instantly claimed invention, Ding is relevant prior art for teaching that HLA-G is expressed much more in human umbilical cord mesenchymal stem cells (HUCMSCs) than MSCs of other origins, and isoform HLA-G5 was also found to be expressed in all of four HUCMSC lines. See Abstract. Ding further teaches that HLA-G5 has been reported to play an important role in allograft acceptance through induction of immunosuppressive/regulatory T cells and a NK cytolysis effect. See page 224, left column.
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 invention of Brodie by selecting umbilical-cord cells positive for HLA-G5, in view of Ding, with a reasonable expectation of success because HLA-G expression is a marker for umbilical-cord-derived MSCs, and the isoform HLA-G5 promotes allograft acceptance.
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