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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/22/2025 has been entered.
Claims 1-20 have been considered on the merits. All arguments have been considered.
Priority
Based on the applicant argument in the remarks filed 12/22/2025 with regard to the previously determined priority date, the priority has been reconsidered and the applicant’s argument was persuasive. Therefore, the earliest filing date of the instant application has been re-determined as the filing date of Application No. 16/857,932 as the provisional application, 62/867,541, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The ‘541 application fails to provide support for the claimed step of isolating a collagen protein from the secretome, and combining the isolated collagen protein with a pharmaceutically acceptable carrier. There is no disclosure of isolating collagen per se or the collagen being combined with the carrier. Thus, the earliest priority date is determined as the filing date of the instant application which is 4/24/2020.
It is noted that the basis of the priority determination is whether the instant application introduces new matter under 112(a). As pointed out by the applicant, the paragraph [0037] is considered to support the limitation of the instant claim 1. However, the same paragraph was not disclosed in the ‘541 application and thus, the instant application as well as the ‘932 application introduce new matter that is not supported from the ‘541 application. As discussed previously, Table 2 of ‘541 application or Fig. 8 of the ‘541 application is not considered to provide the claimed limitation.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Peled et al. (US 9,567,569; IDS ref.) in view of Casper et al. (1999, Molecular Pharmacology), Komaratih et al. (2019, Biochem. Cell. Arch.), Riordan (WO2019083995 A1) and Naughton et al. (US 6,372,494) as evidenced by Niacinamide (2025, NIST), McKewon (2014, Br. J. Radiol.) and Zohora et al. (2023, Heliyon)
Regarding claim 1 and 15, Peled et al. teach a method of culturing and expanding mesenchymal stem cells, and the culture medium used for the method contains an aryl hydrocarbon receptor (AHR) antagonist, and nicotinamide (col. 2, lines 22-26, 56-58). Peled et al. teach resveratrol, a polyhydroxy stilbene, as an AHR inhibitor/antagonist (col. 17, lines 19-27).
Regarding the limitation directed to the concentration of resveratrol being 0.1 mg/ml to 40 mg/ml (claim 1), Peled et al. do not particularly teach the limitation.
Casper et al. teach resveratrol has an antagonist activity on AHR (see entire document). Casper et al. teach that resveratrol binds and translocates AhR to the nucleus, and resveratrol displaced TCDD (i.e. AhR ligand) with an EC50 of 6x10-6 M, and highest concentration tested was 1x10-5 M (p.786, 1st col.; Fig. 1). The concentration of 6x10-6 M, i.e. 6 mM, can be converted to 1.37 mg/ml based on the MW of resveratrol being 228.24 g/mol (according to the instant Remark, p.7), and 1x10-5 M can be converted to 2.28 mg/ml. These concentrations are within the claimed range of 0.1 mg/ml to 40 mg/ml.
Komaratih et al. teach the use of resveratrol at 0.1-1 mM in a culture medium to treat WJ-MSCs in order to obtain secretome (see Abstract; p.4738, 2nd col., last para.). The pretreatment with resveratrol at the concentration tested (i.e. 0.1-1 mM), VEGF-A, HGF and HGF secretion was induced (see Table 1). The concentration of 0.1-1 mM is converted to 0.0228 mg/ml to 0.228 mg/ml, and this range is overlapping with the claimed range.
Furthermore, Riordan teaches a conditioned medium from mesenchymal stem cells (para. 139) and the culture medium contains resveratrol in a concentration of 10-100 mM (para. 132).
It would have been obvious to a person skilled in the art to use the concentration of resveratrol taught by Casper et al., Komaratih et al. or Riordan for the concentration of resveratrol used in the method of Peled et al. because the concentration taught by Casper et al. is known for the function of resveratrol as an AHR inhibitor/antagonist and Komaratih et al.
Peled et al. do not teach the step of collecting the conditioned growth medium and isolating collagen (claim 1).
Naughton et al. teach a method of making a conditioned cell culture medium composition by culturing any eukaryotic cell type including mesenchymal stem cells (Abstract; col.4, lines 46-52). Naughton et al. teach that the conditioned medium contains numerous products that may be isolated and purified therefrom (col. 20, lines 49-51), and exemplified collagen.
It would have been obvious to a person skilled in the art to utilize the conditioned medium produced by mesenchymal stem cells of Peled et al. to isolate collagen with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because Naughton et al. teach that collagen can be isolated from conditioned medium. While Naughton et al. exemplified conditioned medium from culturing fibroblasts as a source of collagen isolation, however, Naughton et al. teach that the conditioned medium can be obtained from any eukaryotic cells including mesenchymal stem cells, and therefore, one skilled in the art would recognize that collagen can be isolated from the conditioned medium of culturing mesenchymal stem cells with a reasonable expectation of success.
Regarding claims 2-3 and 16, it is submitted that the structure of nicotinamide would meet the claimed structure according to Niacinamide (a.k.a. nicotinamide; NIST 2025).
Regarding claims 4, 6 and 15 directed to the culturing under normoxic (claim 4) or hypoxic conditions (claims 4 and 15), Peled et al. teach normoxic or hypoxic conditions are contemplated for the culturing of the MSCs (col. 53, line 65).
Regarding claim 5 directed to the normoxic conditions comprising the O2 content about 15-25%, or claims 7-8 and 15-18 directed to hypoxic conditions comprising the O2 content less than 15%, about 1-10% or about 2-8%, while Peled et al. do not particularly teach the limitation, however, it is well known in the art that normoxic is the oxygen content in the range of about 20-21%; and hypoxia is about 0.4-2% according to McKeown (see Table 1). Thus, the normoxia or hypoxia taught by Peled et al. would meet the limitation of claims 5, 7-8 and 15-18.
Regarding claims 9 and 12 directed to the types of collagen, it is submitted that the combined teachings of Peled et al. and Naughton et al. would inherently meet the limitations of collagen protein being COL1A1 and COL1A2. This is because Peled et al. teach the marrow derived mesenchymal stem cells can be derived from bone marrow, adipose tissue, placenta or umbilical cord blood (col. 2, lines 59-62), and it is well known in the art that COL1A1 and COL1A2 are components of the secretome derived from BMMSCs according to Zohora et al. (see Table 5; p.11, 4. Therapeutic importance and functional dynamics of BMSC-secretomes in degenerative disorders: a giant growing).
Regarding claims 10-11 and 19-20 directed to the pharmaceutically acceptable carrier being configured for topical application to a wound, or the composition being a topical cream, Peled et al. do not teach the limitation. However, Naughton et al. teach that the conditioned cell medium is processed for uses which include wound healing (col.1, lines 8-15; col.5, lines 29-45) and the medium compositions may be used to treat skin conditions topically (col.22, lines 27-44; col. 25, lines 39-45). Naughton et al. teach that the conditioned media may be formulated into pharmaceuticals with a pharmaceutically acceptable carrier in the form of creams (col. 29, lines 14-18). It would have been obvious to a person skilled in the art to prepare the collagen isolated from the conditioned medium derived from culturing BMMSCs of Peled et al. in view of Naughton et al. into a pharmaceutical composition using a known pharmaceutically acceptable carrier for the purpose of treating wound with a reasonable expectation of success.
Regarding claims 13-14 directed to the pharmaceutically acceptable carrier being a saline, or a diluent, Peled et al. teach a pharmaceutically acceptable carrier or diluent such as sterile saline and aqueous buffer solution (col.60, lines 40-45). Thus, it would have been obvious to a person skilled in the art to use a sterile saline as a diluent to prepare the collagen isolated from the conditioned medium of BMSCs of Peled et al. in view of Naughton et al. with a reasonable expectation of success.
Regarding claim 14 directed to the pharmaceutically acceptable carrier being a lubricant, Peled et al. do not teach the limitation. However, Naughton et al. teach that pharmaceutically acceptable excipients such as lubricants (col. 29, lines 21-28). Thus, it would have been obvious to a person skilled in the art to use any known pharmaceutically acceptable carrier including a lubricant taught by Naughton et al. in preparing a pharmaceutical composition comprising collagens isolated from the conditioned medium of BMSCs for the method of Peled et al. in view of Naughton et al. with a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments filed 12/22/2025 have been fully considered but they are not persuasive.
As discussed above under “Priority”, the priority date has been re-determined. It is noted that the priority date does not disqualify any of the references cited in the claim rejections.
Regarding the 103 rejection, the claim rejection now cites new references, Casper et al., Komaratih et al., and Riordan in order to address the newly added limitation directed to the concentration of resveratrol. Thus, the argument based on the newly added concentration is moot based on the newly cited references.
Conclusion
No claims are allowed.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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