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, 5-8, 11-12, 19-21, 26-27, 36-37 and 83) in the reply filed on 12/12/2025 is acknowledged.
Applicant’s election of adipogenic stem cells (ASCs) and glycogen phosphorylase, liver form is also acknowledged.
Claims 2-4, 9-10, 13-18, 22-25, 28-35, 38-55. 57-58, 60-65, 67-70, 72-75, 77-82 and 84-87 have been canceled. Claims 11-12, 56, 59, 66, 71, 76 and 83 have been withdrawn from consideration as being drawn to non-elected subject matter. It is noted that claims 11-12 and 83 are withdrawn because they are directed to the non-elected species (adipocytes). Claim 83 does not clearly disclose what the adipogenic cells are. However, claim 83 is interpreted such that the adipogenic cells are adipocytes obtainable from ASCs. Thus, claim 83 is considered to be directed to non-elected subject matter.
Claims 1, 5-8, 19-21, 26-27, and 36-37 have been considered on the merits.
Information Disclosure Statement
The information disclosure statements filed have been considered except C1 non-patent literature listed in the IDS filed on 5/24/2023 because the list is duplicate as it is also listed in the IDS (C1) filed 9/25/2024. The duplicate is lined through.
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.
Claim Objections
Claims 20-21 are objected to because of the following informalities: there should be a comma after “CD213A1” of claim 20, and “CD115” of claim 21. Appropriate correction 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, 5-8, 19-21, 26, and 36-37 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 discloses the term “long-acting”. The term “long” is a relative term which renders the claim indefinite. The term “long” 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.
Claim 1 discloses the term “therapeutically effective amount”. It is not clear what the scope of this term intends to point out. The claimed product is not particularly limited for any intended purpose, and thus, the term “therapeutically effective amount” cannot be determined and thus, considered indefinite. For search purpose, the term is interpreted as any amount.
Claims 6 and 26 disclose “less than about” in line 2 and 1, respectively. It is not clear what is included or excluded from the claimed range. The term “less than” requires a number for the upper end, i.e. at the maximum requirement, and the term “about” does not provide clear boundary of the range, one cannot determine what the maximum number of the claimed range, and thus, it is indefinite by using “less than” and “about” together in defining the range in the claims.
Claims 6-7 disclose that the composition elicits the claimed effect upon administration to a subject. It is not clear if these effects (increase or decrease of the claimed molecules) are contained to the claimed cells or the subject being administered with the composition. Furthermore, it is not clear what the percentage decrease or increase is referring to expression levels of the claimed proteins or secretion thereof, etc. Clarification is required.
Claims 20-21 disclose that the ASCs express elevated or reduced levels of one or more of the listed markers compared to wild type ASCs and/or unenriched ASCs. The term “wild type ASCs” is not particularly defined in the instant specification, and thus, any ASCs not genetically engineered would be considered as wild type. However, the term “unenriched ASCs” is not clear what the scope is. There is no additional limitation what these ASCs are unenriched for. For example, enriched ASCs for a specific marker protein would be also considered unenriched for other marker proteins. Thus, “unenriched” is considered as a relative term that does not provide as 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.
Furthermore, it is not clear how the claimed ASCs would have elevated or reduced levels of the claimed proteins compared to wild type or unenriched ASCs. It is understood that according to the instant specification the ASCs having elevated or reduced expression level of the claimed proteins appear to be produced via selection step, selectively enriching for the claimed proteins (para. 64 and 72). However, the wild type or unenriched ASCs would inherently contain those ASCs with elevated or reduced expression level of the claimed proteins and thus, the same individual ASCs with elevated or reduced levels of the marker expressions would be in the enriched population of ASCs because there would be individual ASCs with reduced or elevated expression level of any given proteins in a population of wild type or unenriched ASCs. Thus, unless these proteins are engineered to express more or less of the claimed proteins in each individual ASCs, merely enriching the ASCs with the claimed protein from the isolated population of wild type or unenriched population would not provide “elevated” or “reduced” expression of the claimed proteins. Thus, it is not clear what subject matter the instant claims intends to point out.
Claim 27 discloses “at least about” in lines 1 and 2. As the term “at least” requires a number for the lower end, i.e. at the minimum requirement, and the term “about” does not provide clear boundary of the range, one cannot determine what the minimum number of the claimed range, and thus, it is indefinite by using “at least” and “about” together in defining the range in the claims. The court held that claims reciting "at least about" were invalid for indefiniteness where there was close prior art and there was nothing in the specification, prosecution history, or the prior art to provide any indication as to what range of specific activity is covered by the term "about." Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991).
Claim Interpretation
The term “allogenic” in claim 1 does not limit the claimed product as the term is directed to the intended use of the product.
The term “non-immunogenic” does not provide any structure to the claimed cells, and yet the claimed function is determined when the product is used, thus, the term is interpreted as an intended use/result and thus, the limitation does not provide any weight in determining patentability of the claimed product.
The term “long-acting” does not provide any structure to the claimed product and this limitation is considered the function when the product is used in a method. Thus, in the absence of any structural feature claimed for such function other than adipogenic cells, this limitation is considered as an intended result from the intended result of the claimed product.
As discussed above, the phrase “therapeutically effective amount” is interpreted as any amount.
Based on the above analyses, claim 1 is interpreted as a composition comprising substantially pure adipogenic cells.
Claims 5-7 and 36 are directed to the features when the claimed product is administered to a subject, and thus, the limitations of the claims are considered as intended results rather than providing any structure to the claimed product. Thus, claims 5-7 are interpreted the same as claim 1.
Claims 20-21 are interpreted as the ASCs expressing elevated levels of the listed markers compared to wild type ASCs.
Claim 26 is interpreted as the ASCs do not express the any surface marker as claimed.
Claim 27 is interpreted as the composition comprising ASCs, and at least 90% of the ASCs express one of the listed markers.
Claim 37 is interpreted as the composition comprising the adipogenic stem cells comprising a heterologous nucleic acid.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 5-8, 19-21, 26-27, and 36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception, a law of nature or a natural phenomenon, without significantly more.
Claims 1, 5-8, 19-21, 26-27, and 36 are directed to a statutory category, e.g., a composition of matter (Step 1:YES).
The claim(s) recite(s) a composition comprising adipogenic cells, and the adipogenic cells are adipogenic stem cells. The adipogenic stem cells are nature-based products, and the nature-based product is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. In this case, adipogenic stem cells (ASCs), which is considered identical to adipose-tissue derived stem cells (adipose stem cells) known in the art, disclosed in the claims are considered naturally occurring products. The instant specification discloses that the ASCs are isolated from adipose tissue, and there is no indication that the claimed ASCs have any structural or functional characteristics that are significantly different from naturally occurring counterparts. Thus, the claimed composition comprising ASCs does not have markedly different characteristics from what occurs in nature, and is a “product of nature” exception. Claims 5-7 disclose that the capability of the claimed ASC composition when administered to a subject, and the results of the administration do not particularly provide any additional structure to the ASCs as these features are known to be inherent to ASCs. Regarding claim 36 directed to the ASCs expressing glycogen phosphorylase, liver form, it is known in the art that human ASCs would inherently express the protein according to Chen et al. (2018, Stem Cell Research & Therapy). Accordingly, the claims are directed to a judicial exception (Step 2A Prong One: YES).
This judicial exception is not integrated into a practical application because there is no additional element that would integrate the judicial product into any improvement in their function or the use of a particular treatment or applying or using the judicial exception in some other meaningful way. Thus, the judicial exception is not integrated into a practical application (STEP 2A Prong Two: NO).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because as discussed above, the marker expression or the results from the use of the claimed product are either inherent or does not provide any structure to the claimed product. Thus, there is no additional elements adding significantly more to the judicial exception (STEP 2B: NO).
Based on the above analysis, the claimed product is not eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 102
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.
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.
Claim(s) 1, 5-8, 19-21, 26-27 and 36-37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gimble et al. (US 2008/0095750A1; IDS ref.) as evidenced by Kolodziej et al. (2019, Adipocyte) and Chen et al. (2018, Stem Cell Research & Therapy).
Gimble et al. teach a purified population of adipose-derived stem cells (ASCs) from adipose tissue (para. 81). Gimble et al. teach that the ASCs are non-immunogenic (para. 9 and 94). As discussed in the claim interpretation, “allogenic” and “long-acting” do not provide any weight in determining the patentability as they are directed to the intended use rather than the structure of the claimed product. Regarding “therapeutically effective amount”, it is interpreted as any amount. Furthermore, Gimble et al. teach the ASCs in an amount effective to reduce levels of psychosine (para. 11-12), and this teaching would meet the limitation.
Regarding claims 5-7, as discussed in the claim interpretation, they are considered the same as claim 1. Thus, the teachings of Gimble et al. meet the limitations.
Regarding claim 19 directed to the characteristics of the ASCs, as Gimble et al. teach the identical cell population as the claimed composition, it is considered that the ASCs of Gimble et al. would inherently contain the characteristics of the claimed cells in the absence of any evidence to the contrary. Furthermore, Kolodziej et al. teach that the human adipose-derived stem cells have glucose uptake from 6.13 ± 0.58 mmol/L to 7.73 ± 0.37 mmol/L (Figure 7(a)) (p.260, 1st col.). Thus, the claimed range of glucose uptake is inherently met by the teaching of Kolodziej et al.
Regarding claims 20-21 directed to ASCs expressing elevated levels (claim 20) or reduced levels of the claimed proteins, Gimble et al. do not particularly teach the limitations. However, it is considered that wild type ASCs, like those human ASCs from adipose tissue taught by Gimble et al., would necessarily contain ASCs having elevated or reduced expression levels of these proteins among the individual ASCs in the population as each individual ASC would have different expression levels of these proteins. As the claimed ASCs are from the same source as the ASCs of Gimble et al., it is considered that the ASCs of Gimble et al. would inherently contain those ASCs expressing elevated levels of markers of claim 20 or reduced levels of markers of claim 21. It is submitted that the claimed ASCs are not particularly claimed such that they are enriched for a specific markers.
Regarding claim 26 directed to negative expression of the claimed markers in ASCs, Gimble et al. teach CD14 and CD45, for example, are negative in ASCs (Table 2).
Regarding claim 27 directed to the positive expression of the claimed markers, Gimble et al. teach positive markers including CD44, CD29, CD73, CD90 and CD105 in ASCs (Table 2).
Regarding claim 36 directed to the ASCs expressing glycogen phosphorylase, liver form, Gimble et al. do not particularly teach the limitation. However, it is considered that ASCs would inherently be capable of expressing glycogen phosphorylase, liver form (PYGL), according to Chen et al. (p.8, 1st col.; Fig. 7).
Regarding claim 37 directed to the ASCs comprising a heterologous nucleic acid, Gimble et al. teach that genetically modified ASCs and the use of expression cassette containing the transgene incorporated into a genetic vector suitable for delivering the transgene to the cells (paras. 90-93).
Thus, the reference anticipates the claimed invention.
Claim(s) 1, 5-8, 19-21, 26-27 and 36 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kastrup et al. (US 2018/0325957A1) as evidenced by Kolodziej et al. (supra) and Chen et al. (supra).
Kastrup et al. teach an isolated substantially homogenous population of human adipose-derived stem cells (ASCs) from adipose tissue (para. 40). Kastrup et al. teach that the ASCs are immunosuppressive (para. 96), and this teaching would meet the “non-immunogenic” property. As discussed in the claim interpretation, “allogenic” and “long-acting” do not provide any weight in determining the patentability as they are directed to the intended use rather than the structure of the claimed product. Regarding “therapeutically effective amount”, it is interpreted as any amount. Furthermore, Kastrup et al. teach the ASCs in an amount for therapeutic use (para. 146).
Regarding claims 5-7, as discussed in the claim interpretation, they are considered the same as claim 1. Thus, the teachings of Kastrup et al. meet the limitations.
Regarding claim 19 directed to the characteristics of the ASCs, as Kastrup et al. teach the identical cell population as the claimed composition, it is considered that the ASCs of Kastrup et al. would inherently contain the characteristics of the claimed cells in the absence of any evidence to the contrary. Furthermore, Kolodziej et al. teach that the human adipose-derived stem cells have glucose uptake from 6.13 ± 0.58 mmol/L to 7.73 ± 0.37 mmol/L (Figure 7(a)) (p.260, 1st col.). Thus, the claimed range of glucose uptake is inherently met by the teaching of Kolodziej et al.
Regarding claim 20 directed to ASCs expressing elevated levels of the claimed proteins, Kastrup et al. do not particularly teach the limitations. However, it is considered that wild type ASCs, like those human ASCs from adipose tissue taught by Kastrup et al., would necessarily contain ASCs having elevated or reduced expression levels of these proteins among the individual ASCs in the population as each individual ASC would have different expression levels of these proteins. As the claimed ASCs are from the same source as the ASCs of Kastrup et al., it is considered that the ASCs of Kastrup et al. would inherently contain those ASCs expressing elevated levels of markers of claim 20. It is submitted that the claimed ASCs are not particularly claimed such that they are enriched for a specific markers.
Regarding claim 21 directed to ASCs expressing reduced levels of the claimed proteins, Kastrup et al. teach that the ASCs upon INF-gamma stimulation, CD9 is reduced (para. 118), and this teaching would meet the limitation of claim 21.
Regarding claim 26 directed to negative expression of the claimed markers in ASCs, Kastrup et al. teach at most 2% of the ASCs express CD14 and CD45 (para. 101).
Regarding claim 27 directed to the positive expression of the claimed markers, Kastrup et al. teach at least 95% of the ASCs express CD90, CD73, CD13, CD29 (para. 101).
Regarding claim 36 directed to the ASCs expressing glycogen phosphorylase, liver form, Kastrup et al. do not particularly teach the limitation. However, it is considered that ASCs would inherently be capable of expressing glycogen phosphorylase, liver form (PYGL), according to Chen et al. (p.8, 1st col.; Fig. 7).
Thus, the reference anticipates the claimed invention.
Claim(s) 1, 5-8, 19-21, 26-27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Marycz et al. (2016, J. Cell. Mol. Med.).
Marycz et al. teach an isolated population of ASC from horses (see entire document). As discussed in the claim interpretation, “allogenic” or “long-acting” does not limit the claimed product as they are directed to an intended use/purpose. While Marycz et al. do not particularly disclose “non-immunogenic”, as Marycz et al. teach that ASCs are immunomodulatory and immunosuppressive (p.2, 1st col.), it is considered that the ASCs of Marycz et al. are inherently non-immunogenic.
Regarding claims 5-7, as discussed in the claim interpretation, they are considered the same as claim 1. Thus, the teachings of Marycz et al. meet the limitations.
Regarding claim 19 directed to the characteristics of the ASCs, as Marycz et al. teach the identical cell population as the claimed composition, it is considered that the ASCs of Marycz et al. would inherently contain the characteristics of the claimed cells in the absence of any evidence to the contrary.
Regarding claim 20 directed to ASCs expressing elevated levels of the claimed proteins, Marycz et al. teach a flow cytometry using anti-LAMP2 antibody to isolate LAMP2 expressing ASCs (p.5, Autophagy assessment). This process would inherently enrich the ASCs positive for LAMP2, also known as CD107b of claim 20. Thus, Marycz et al. teach that ASCs expressing elevated levels of CD107b. Furthermore, it is submitted that considering a population of ASCs of Marycz et al. is heterogenous, it is considered that the population of ASCs of Marycz et al. would comprise those with elevated or reduced levels of any given marker expression. Thus, the population of isolated ASCs of Marycz et al. would inherently meet the limitation of claim 20.
Regarding claim 21 directed to ASCs expressing reduced levels of the claimed proteins, the same analysis discussed above would be applicable to claim 21. While Marycz et al. do not particularly teach the limitations, however, it is considered that wild type ASCs, including horse ASCs of Marycz et al., would necessarily contain ASCs having reduced expression levels of these proteins among the individual ASCs in the population as each individual ASC would have different expression levels of these proteins. As the claimed ASCs are from the same source of adipose tissue as the ASCs of Marycz et al., it is considered that the ASCs of Marycz et al. would inherently contain those ASCs expressing reduced levels of markers of claim 21. It is submitted that the claimed ASCs are not particularly claimed such that they are enriched for a specific markers.
Regarding claim 26 directed to negative expression of the claimed markers in ASCs, Marycz et al. teach lack of expression CD45 (p.6, 2nd col.)
Regarding claim 27 directed to the positive expression of the claimed markers, Marycz et al. teach positive markers including CD44, CD90 and CD105 (p.6; Immunophenotyping and multipotency assay).
Regarding claim 36, as discussed above, the cells of Marycz et al. are identical to the claimed cells in the composition. Thus, the ASCs of Marycz et al. are considered inherently expressing the claimed protein, i.e. glycogen phosphorylase, liver form, in the absence of any evidence to the contrary.
Thus, the reference anticipates the claimed invention.
Conclusion
No claims are allowed.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631