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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/15/2026 has been entered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. JP2020-080760, filed on 04/30/2020.
Acknowledgement of the claim for foreign priority under 35 U.S.C. 119 and receipt of the certified priority document was formally requested in the Remarks dated 04/15/2026, after the Final Rejection dated 12/16/2025 was sent out. As stated previously in said Final Rejection, please see the above acknowledgement of foreign priority and all associated priority documents under 35 U.S.C 119. Furthermore, priority is acknowledged of PCT/JP2021/014552 dated 04/05/2021, along with any documents associated thereof.
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.
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.
Claims 8, 10, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Raghunath et al. (US 2012/0322152 A1) in view of Nojima et al. (EP 3 578 639 A1)
Regarding Claim 8: Raghunath teaches a method of increasing cellular proliferation using macromolecular crowding via carbohydrate-based macromolecules to promote the growth of stem cells while preserving their multipotentiality. (57) In addition, Raghunath teaches use of human mesenchymal stem cells to be used in culture. (0006) Specifically, Raghunath teaches that macromolecules when used in culture exert an excluded volume effect (EVE) which speeds up specific enzymatic steps required for collagen deposition, thus resulting in a 20-30 fold increase of collagen-specific ECM deposition. (0011) in addition, Raghunath states that when used in vitro, macromolecular crowding is a tool which can recapitulate the in vivo physiological environment and cause enhanced deposition of key ECM proteins. (0078) One specific embodiment of the invention uses polyvinylpyrrolidone as the macromolecule (0099) and figure 21 demonstrates use of polyvinylpyrrolidone at both 100 ug/mL (0.1 mg/mL) and 500 ug/mL (0.5 mg/mL), which reads on the claimed range of use of polyvinylpyrrolidone at a concentration between 0.2-0.6 mg/mL. (pg. 24, Fig. 21) As demonstrated in the figure below, use of PVP at both concentrations significantly increased cellular proliferation when compared to the control which used no macromolecules.
PNG
media_image1.png
628
934
media_image1.png
Greyscale
Raghunath fails to teach use of ß-nicotinamide mononucleotide in the culture medium.
Nojima et al. teaches use of a material further accelerating the growth of pluripotent stem cells, importantly without imparing pluripotency thereof. (57) Specifically, Nojima found that use of b-nicotinamide mononucleotide accelerated the growth of stem cells and aided in maintaining their pluripotency. (0009)
Regarding claims 10 and 11: Raghunath teaches use of the media comprising polyvinylpyrrolidone for the culture of adult mesenchymal stem cells. (0006)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the culture method taught by Raghunath of use of polyvinylpyrrolidone in a medium for mesenchymal stem cells with the teachings of Nojima to create a culture system for stem cells comprising carboxymethyl cellulose at 0.1-0.5 mg/mL and ß-nicotinamide mononucleotide. One would have had motivation and a reasonable expectation of success at doing so based on the teachings of Nojima, who state that use of b-nicotinamide mononucleotide specifically aids in the acceleration of the growth of pluripotent stem cells and acts to preserve their pluripotency.
Claims 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Raghunath et al. (US 2012/0322152 A1) in view of Nojima et al. (EP 3 578 639 A1), Keenan et al. (Recombinant Human Albumin in Cell Culture: Evaluation of Growth-Promoting Potential for NRK and SCC-9 Cells In Vitro, 1997), and Sargent (Expansion of Mesenchymal Stem Cells in Blood-free, Chemically Defined Media, 2018).
The teachings of Raghunath and Nojima are set forth above. Both fail to teach use of the claimed concentration of recombinant albumin.
Regarding Claim 9: Sargent teaches a method of culture for mesenchymal stem cells (MSC) in media comprising recombinant albumin as compared to serum-derived albumin and transferrin with FBS as a control. (Pg 2, Mesenchymal Stem Cell Culture Performance) The MSCs in culture with recombinant albumin showed equivalent or superior performance when compared to serum-derived albumin (pg 2, Mesenchymal Stem Cell Culture Performance) and it is advantageous to use recombinant albumin as opposed to serum-derived due to the chemically defined nature of recombinant albumin. Serum-derived albumin is variable from batch to batch and risks introducing biological contaminants to culture. (Pg 1, Stem Cell Media) This reads on the claimed method of culturing stem cells in a medium comprising recombinant albumin.
Sargent fails to teach use of recombinant albumin at a final concentration of 0.05-1 mg/mL.
Keenan teaches use of recombinant albumin in the culture of both NRK and SCC-9 cells at a range of between 0-11 mg/mL of rHA. (Pg 245-246, Figures 1 and 2) This reads on the claimed range of recombinant albumin being present in the medium at a final concentration of 0.05-1 mg/mL.
Regarding Claims 10 and 11: Sargent teaches a method of culturing mesenchymal stem cells in a media comprising recombinant albumin. (Pg 2, Mesenchymal Stem Cell Culture Performance)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Raghunath of use of polyvinylpyrrolidone in a stem cell culture media with the culture method taught by Sargent (use of recombinant albumin) and Keenan (the specified final concentration of rHA at 0-11 mg/mL) to incorporate rHA at 0.05-1 mg/mL in the claimed medium. One would have had motivation and a reasonable expectation of success at doing so based on the teachings of Sargent who states use of recombinant albumin for mesenchymal stem cell culture is advantageous to serum-derived albumin and Keenan who demonstrates successful culture of NRK and SCC-9 cells within the claimed range of 0.05-1 mg/mL.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Raghunath et al. (US 2012/0322152 A1) in view of Nojima et al. (EP 3 578 639 A1) and Froud (The development, benefits, and disadvantages of serum-free media, 1999, abstract)
The teachings of Raghunath and Nojima are set forth above. Both fail to teach the advantages of serum free media.
Regarding claim 12: Froud teaches that serum-free culture is beneficial as it reduces process variability and removes a potential source of infections agents.
It would have been obvious to a person of ordinary skill in the art to combine the teachings of Raghunath and Nojima with the teachings of Froud to create a serum free culture media for the culture of stem cells comprising polyvinylpyrrolidone and beta nicotinamide mononucleotide. One skilled in the art would have had motivation to make the medium serum free due to the teachings of Froud, who states that serum-free culture is beneficial as it reduces process variability and removes a potential source of infectious agents.
Response to Arguments
Applicant's arguments filed 10/01/2025 have been fully considered but they are not persuasive. Applicant argues that Maiese fails to teach use of the specific isomer of NAM required for the method of the claimed invention, NAD+. This is persuasive, as Maiese teaches use of NAM and attributes the benefit of culture to be found there. However, Nojima et al. teaches use of specifically NAD+ and, as discussed above, details how it was found that NAD+ preserves the pluripotency of stem cells in culture while simultaneously accelerating their growth rate. As such, the teachings of Nojima have been incorporated into the 35 U.S.C. 103 rejection of claims 8-12.
Applicant has elected to add new claim 12 and argues that Raghunath uses media containing serum. This is true, however, serum itself is not required for the method of the invention as Raghunath merely states that a variety of methods for maintaining cell culture may be used as known in the art, which includes serum. (0107) The substance of the invention taught by Raghunath is use of macromolecular crowding agents such as polyvinylpyrrolidone in order to promote the growth of stem cells in vitro. (57) In addition to this, the teachings of Froud have been incorporated into the 35 U.S.C 103 rejection of claim 12. Froud clearly states reasons for not incorporating serum into cell culture media including serum itself being a potential risk of contamination for culture, motivating a person skilled in the art to avoid incorporating serum into the culture media.
Based on the above discussion, the 35 U.S.C. 103 rejections of claims 8-12 is maintained on the record.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HANNA MARIE THUESON/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights