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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/18/2025 has been entered.
Response to Amendment
The amendment filed 4/18/2025, amending claims 18, 20, 24, 25, 29, 31, 34, 36, and cancelling claims 19, 22, 30, 33, 35, 38 is acknowledged. Claims 18, 20, 24, 25, 29, 31, 34, and 36 are pending and under examination.
Applicant’s amendments to the claims have overcome the 103 rejection
previously set forth in the Non-Final Office Action mailed 01/31/2025.
Withdrawn Rejections
The rejection of claims 18, 20, 24, 25, 29, 31, 34, 36 under 103 as being unpatentable over Taguchi in view of Nishimura is withdrawn. Applicant added the new limitation of preserving a mammalian cell in a lactated Ringer’s solution comprising 2.0 to 6.0% (w/v) of trehalose or a salt thereof, 4.0 to 7.0% (w/v) of dextran or a salt thereof, and sodium bicarbonate as a pH modifier, and having a pH of 6.5 to 8.5 in the methods of preserving a mammalian cell recited in claims 18, 29, and 34, which is not taught by the combination of Taguchi and Nishimura.
Response to Arguments
Applicant’s arguments filed 4/18/25 pertaining to the teachings of Taguchi (in combination with Nishimura) have been considered but are moot because the new ground of rejection does not rely on Taguchi as applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed 4/18/25 have been fully considered but they are not persuasive.
The Applicant argues that “it cannot be said that it is well known to use sodium bicarbonate as a pH modifier”, and requested art to demonstrate this point. As requested, the Examiner cites an excerpt from Thermo Fisher’s Cell Culture Media Supplements webpage, which states “Sodium bicarbonate (NaHCO3) is a common buffer used in cell culture for maintaining the pH of the medium in the presence of 4–10% carbon dioxide. In addition, sodium bicarbonate provides some nutritional benefits and is rarely toxic to cells” (pg. 3).
Additionally, the Applicant argues that the use of sodium bicarbonate as a pH modifier in the instant case results in unexpected results, with cell viability increasing by about 25. Although the Applicant has amended the claims to require the presence of sodium bicarbonate in the preservation solution, it is noted that the resulting cell viability rate is not recited in the rejected claim(s) and is not considered a limitation. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further, the fact that the inventor has recognized another advantage which would flow naturally from the structure of sodium bicarbonate (i.e., acting as a pH modifier) following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Additionally, as discussed in more detailed below in the 103 rejection, Campbell (Campbell, Lia H., and Kelvin GM Brockbank. "Culturing with trehalose produces viable endothelial cells after cryopreservation." Cryobiology 64.3 (2012): 240-244.- NPL #1 in IDS submitted 1/23/2023) previously taught that adjusting the pH of a mammalian cell preservation solution using sodium bicarbonate resulted in significantly better cell survival results compared to using HEPES as a buffer (pg. 242, col 2, para 1).
Priority
Applicant’s claim for the benefit of prior-filed application PCT/JP2020/017586, filed on 04/24/2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d).
While a certified copy of the foreign patent application JP 2019-085499, filed on 04/26/2019 is provided with the instant application, a certified English translation of said foreign patent application has not been provided.
Claim Interpretation – Maintained (for reference)
Claims 18, 29, and 34 recite “trehalose or a derivative thereof, or a salt thereof”. The examiner interprets this recitation to be defined by paragraphs 0019-0020 of the specification, copied below:
[0019]
A trehalose derivative among the above trehalose groups is not particularly limited as long as one or more sugar units are linked to a disaccharide trehalose to yield a glycosyl trehalose group. Examples of the glycosyl trehalose group include glucosyl trehalose, maltosyl trehalose, or maltotriosyl trehalose.
[0020]
Examples of a salt of trehalose or a derivative thereof among the above trehalose groups include an acid addition salt (e.g., a hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate, sulfate, acetate, propionate, toluenesulfonate, succinate, oxalate, lactate, tartrate, glycolate, methane sulfonate, butyrate, valerate, citrate, fumarate, maleate, malate), a metal salt (e.g., a sodium salt, potassium salt, calcium salt), an ammonium salt, or an alkylammonium salt. Note that each salt is used in a solution form upon use, and the action is preferably the same as in the case of trehalose. Each salt compound may form a hydrate or solvate. Also, any of them may be used singly or two or more kinds thereof may be used in combination, if appropriate.
Claim Rejections - 35 USC § 103 – New, necessitated by amendments
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.
Claim(s) 18, 20, 24, 25, 29, 31, 34, and 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nishimura (US 20160120170 A1, published May 5, 2016; from IDS submitted 01/18/22), and further in view of Campbell (Campbell, Lia H., and Kelvin GM Brockbank. "Culturing with trehalose produces viable endothelial cells after cryopreservation." Cryobiology 64.3 (2012): 240-244.- NPL #1 in IDS submitted 1/23/2023), as evidenced by Thermo Fisher (see “Cell Culture Media Supplements_Thermo Fisher Scientific – US”; last accessed 9/22/2025).
Regarding claims 18, 25, 29, and 34, Nishimura teaches a method of preserving a mammalian cell, comprising a step of preserving a mammalian cell in a lactated Ringer’s preservation solution comprising 2.0 to 6.0% trehalose (w/v) of trehalose, or a salt thereof, and 4.0 to 7.0% (w/v) of dextran or a salt thereof (LR= Lactec, a lactated Ringer’s solution) (Example 1, e.g., [0055], Table 1).
Additionally, Nishimura teaches adding a mammalian cell to the solution (claim 34) [0033].
Further, while Nishimura does not explicitly teach administering the solution comprising the preserved mammalian cell to a subject in need of mammalian cell transplantation, the claims of Nishimura are directed to a method for preserving a mammalian cell in a solution for cell transplantation and said solution for cell transplantation, similar to the instant case. Because the prepared solution of Nishimura is for cell transplantation, one of ordinary skill in the art would conclude that the cell transplantation referenced by Nishimura would be in a subject in need thereof (i.e., the solution and cells would be administered to a subject). Additionally, Nishimura teaches the present invention being useful in the field of medical transplantation in regenerative medicine or the like and the field of cancer treatment [0022, 0130], and references treatments such as bone-marrow transplantation in patients, tissue stem cell transplantation treatment of traumatic disease and tissue degeneration disease, and cancer immune cell therapy comprising taking immune cells outside the body and later returning the cells to the inside of the body (e.g., via vaccines) when providing background on the claimed invention. (claims 25 and 29) [0002].
Nishimura does not explicitly teach the solution further comprising sodium bicarbonate as a pH modifier, and is silent on the pH of the solution. However, Nishimura teaches that the solution may comprise bicarbonate Ringer’s solution, which reasonably suggests adding sodium bicarbonate to the solution for cell transplantation [0035]. Additionally, Nishimura notes that the solution can be supplemented with additives, such as a buffer (e.g., phosphate buffer, sodium acetate buffer) and basal media (e.g., DMEM, which contains sodium bicarbonate) [0036].
Campbell teaches a method of preserving a mammalian cell, comprising preserving the cells in a solution comprising 0.2-0.4 M trehalose in sodium bicarbonate buffered Eagles minimum essential medium at pH 7.4 (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the method taught by Nishimura with the method taught by Campbell by adding the sodium bicarbonate taught by Campbell to the solution taught by Nishimura. One would have a reasonable expectation of success because sodium bicarbonate is a type of buffer and Nishimura teaches that the solution used for preserving mammalian cells by Nishimura can comprise additional additives such as buffers. Additionally, sodium bicarbonate is a well-known buffer in the art, as taught by Campbell and evidenced by Thermo Fisher, and is rarely toxic to cells (Campbell- pg. 242, col 2, para 1; Thermo Fisher- pg. 3). An artisan would be motivated to combine the methods to include sodium bicarbonate because as taught by Campbell, preservation solutions comprising trehalose and sodium bicarbonate yielded significantly better results following cryopreservation and thawing (e.g., cell metabolic activity) compared to preservation solutions comprising trehalose and HEPES (pg. 242, col 2, para 1 and 2).
Regarding claims 20, 31, and 36, Nishimura teaches the solution further comprising a polysaccharide (i.e., reads on the solution comprising dextrans, dextran derivatives, etc.) [0042, 0043].
Regarding claim 24, Nishimura teaches a preservation period of anywhere from 12 hours to 21 days, preferably 3 to 12 days [0037, 0072, 0076] (Table 1).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ALLISON MARIE JOHNSON/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638