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 .
Applicant’s amendment and response filed on 12/30/2025 has been received and entered into the case.
Claims 7 and 9 have been canceled, claims 1-5 and 15-20 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 6, 8 and 10-14 have been considered on the merits. All arguments have been considered.
Response to Amendment
The claim objections have been withdrawn due to the instant amendment.
The claim rejections under 35 USC 112 have been withdrawn due to the instant amendment except those maintained (see below). New 112 rejections have been necessitated by the instant amendment (see below).
The claim rejections under 35 USC 103 have been withdrawn due to the instant amendment. A new 103 rejection is presented to address the instant amendment.
Priority
A certified English translation of the priority document was filed on 12/30/2025. The foreign priority claim is granted and the earliest filing date of the instant application is determined as 4/13/2021.
Claim Rejections - 35 USC § 112 (New Rejection)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 6, 8 and 10-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The instant amendment introduces new limitations directed to:
trypsin-EDTA solution at 40% to 60% in volume concentration during the step (2) of claim 6: The concentration of “40% to 60%” is disclosed for tryple-EDTA enzyme in the originally filed specification, and the amendment is now directed to trypsin-EDTA which is different from tryple-EDTA, the concentration of 40% to 60% directed to trypsin-EDTA is not supported.
the trypsin-EDTA solution comprises trypsin and EDTA, and a concentration of the trypsin in the trypsin-EDTA solution is 0.25g/100ml: The concentration of trypsin in the trypsin-EDTA solution being 0.25g/100ml is not supported by the instant specification as the concentration of trypsin in the trypsin-EDTA is disclosed as 0.1% to 0.15% (para. 26).
the cryopreservation liquid comprises dimethyl sulfoxide (DMSO) at a concentration of 55g/100ml and dextran 40 at a concentration of 5g/100ml (claim 14). There is no disclosure for the ”55g/100ml of DMSO and “dextran 40” at a concentration of “5g/100ml”.
Thus, the instant amendment introduces new matter to the instant application.
In amended cases, subject matter not disclosed in the original application is sometimes added and a claim directed thereto. Such a claim is rejected on the ground that it recites elements without support in the original disclosure under 35 U.S.C. 112, first paragraph, Waldemar Link, GmbH & Co. v. Osteonics Corp. 32 F.3d 556, 559, 31 USPQ2d 1855, 1857 (Fed. Cir. 1994); In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981). See MPEP § 2163.06 - § 2163.07(b) for a discussion of the relationship of new matter to 35 U.S.C. 112, first paragraph. New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.
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 6, 8 and 10-14 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.
The claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
Claim 6 discloses the term “pariduval”. There is no definition given to this term in the specification. There is no known term in the art as this is not an English term. Without knowing the meaning of this term, and without any definition given in the specification, it is not clear what subject matter the instant claims intend to point out. Clarification is required. The term “pariduval mesenchymal stem cell” is interpreted as mesenchymal stem cells from parietal decidua as this is the source of the cells according to the claimed method.
Claim 6 discloses the term “high-glucose” in line 6. The term “high” is a relative term which renders the claim indefinite. The term “high” 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. While a high-glucose DMEM is known in the art as a commercially available product, however, the term “high-glucose” in the claim is not particularly defined and there is no standard for the term, and thus, the scope of the “high” is not clear what to be included or excluded in terms of the glucose concentration.
Claim 6 discloses the concentration of the trypsin-EDTA solution being at 40-60% in volume concentration and then trypsin concentration is 0.25g/100 ml. It is not clear which concentration is intended for trypsin-EDTA. Clarification is required. As indicated above, the instant specification discloses none of these concentrations. For search purpose, the trypsin concentration for trypsin-EDTA is 0.25% (0.25g/100ml) as the 40-60% was referred to Tryple-EDTA enzyme which has been removed from the claims.
Claim 6 discloses “SCGF” and it stands for “stem cell growth factor”. It is not clear what this term intends to point out. While applicant indicates that it would mean SCF, however, there is no indication in the claim that the “stem cell growth factor” would be stem cell factor (SCF). As the term “stem cell growth factor” can be interpreted as any growth factor for stem cell, the scope of the term “SCGF” is vague what it refers to and thus, indefinite.
Claim Rejections - 35 USC § 103 (New Rejection)
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) 6 and 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN’363 (of record) in view of CN’521 (of record), CN’748 (of record) and CN’717 (of record), and as evidenced by Decidua (of record).
CN’363 teach a method of isolating MSCs from placenta decidua vera tissue and the method comprises isolating the tissue, shredding and cleaning, digesting using a tissue digestion liquid followed by terminating the digestion, filtering the indigested tissue block, collecting cell suspension after centrifugation, removing the supernatant, cleaning the precipitated cells (cell pellet), and repeating centrifugating (see Claims 1, steps (1)-(5)). The MSCs cultured in a selective medium, and passaged to P3 for placenta decidua vera MSCs. CN’363 teach the use of the tissue digestion liquid including H-DMEM (high-glucose DMEM) comprising 10 mg/ml of collagenase type I (p.3, step (5)).
It is noted that the term “decidua vera” is identical to the term “decidua parietal” (see Decidua, Wikipedia).
As indicated above, the term “pariduval mesenchymal stem cell (PMSCs)” is interpreted as “mesenchymal stem cell derived from parietal decidua”. As CN’363 teach the mesenchymal stem cells from parietal decidua, the mesenchymal stem cells of CN’363 are considered to meet the claimed PMSCs.
Regarding the step of cutting and the tissue blocks of step (1), it is considered that the shredding step and the shreds of CN’363 meet the limitation. CN’363 do not teach the tissue blocks of 1-4 mm3. However, the size of shreds taught by CN’363 would be readily adjusted for the desired outcome of tissue digestion and subsequent isolation of MSC. Furthermore, CN’521 teach that placental decidua tissue is cut into 2 mm3 pieces (p.3, step (2)). Still further, CN’748 teach cutting the parietal decidua into 1-4 mm3 (p.3). Thus, it would have been obvious to a person skilled in the art to adjust the size of the tissue shreds taught by CN’521 with a reasonable expectation of success.
Regarding the cleaning step of step (1), while CN’363 teach the cleaning step after the shredding the placenta decidua vera (i.e. shreds cleaning; Claim 1, step (1) at p.1; Step 3 of p.4), however, it does not disclose a cleaning solution. However, it would have been obvious to a person skilled in the art to use a solution for the purpose of cleaning the shredded tissue of CN’363.
Regarding tissue block digestion of step (2), CN’363 teach the digestion step (p.4, Step 3) using a tissue digestion liquid comprising high glucose DMEM and collagenase type I and DNAase. However, they do not teach the tissue digestion being under constant temperature under oscillation of step (2) of claim 6.
CN’748 teach the use of constant temperature under oscillation at 37°C (p.5, Step 3). As CN’748 is directed to the method of preparing the same decidua parietalis MSCs, it would have been obvious to use the teachings of CN’748 for the method of CN’363 with a reasonable expectation of success.
Regarding the tissue digestion solution being a high-glucose DMEM comprising trypsin-EDTA comprising the trypsin in the trypsin-EDTA solution at 0.25g/100ml (0.25%) and collagenase type II at 8-12 mg/ml (step (2) of claim 6), CN’363 teaches a tissue digestion liquid for obtaining MSCs from placenta decidua comprises DMEM in high glucose culture medium; H-DMEM) (p.4, steps 3-4).
However, CN’363 does not teach the use of trypsin-EDTA and the concentration of trypsin in the trypsin-EDTA solution.
CN’717 (p.4) teach the digestive solution comprising trypsin with a mass percentage of 0.2-0.3% and EDTA at 0.003-0.005% (p.2, claim 8), and 10 mg type II collagenase (p.4, Example 1(2)). Thus, it would have been obvious to a person skilled in the art to use the tissue digestion solution of CN’717 comprising 0.25% trypsin-EDTA and collagenase type II at 8-12 mg/ml in H-DMEM for the same purpose of digesting the parietal decidua as taught by CN’363 with a reasonable expectation of success. The use of trypsin-EDTA for tissue digestion is extremely well known in the art and thus, the use of known ingredient for the known purpose is obvious.
Regarding the step (3) directed to the washing the precipitate with normal saline, resuspending, centrifuging, removing the resulting supernatant, and resuspending a resulting precipitate with a selective medium to obtain a PMSC suspension, CN’717 teaches the step (3), separation, in Example 1, and this step is directed to resuspending precipitate after washing using normal saline, resuspending, and centrifugation after digestion, and the resulting precipitate is resuspended in DMEM/F12 medium to obtain a subpluripotent stem cell suspension and subjected to culturing step of (4). The DMEM/F12 for resuspending the precipitate is considered to meet the selective medium.
Regarding the step (4) of claim 6 directed to the culturing primary cells in a culture flask in an incubator, while CN363 do not particularly disclose the details of culturing using a flask and an incubator, one skilled in the art would have at once envisaged that the process of culturing taught by CN363 would necessarily involve a culture flask and an incubator.
Regarding the step (5) directed to the cell confluency being greater than 80%, it is extremely well known in the art that cultured cells would be passaged for the next generation (i.e. subculturing) when they are confluent, and CN’521 teach that subculturing is when the confluence rate reaches over 80% (p.4, 4th para. from the bottom).
Regarding step (6), CN’363 teaches the placenta decidua vera MSC primary cell is passaged to P3 generation (p.4, Step 7). However, CN’363 do not teach the cryopreserving the cells in a liquid nitrogen after programmed cooling. CN’521 teach the use of programmed cooling device and a liquid nitrogen tank for cryopreserving parietal decidual tissue (p.4, (3) Cryopreservation of placental wall decidua tissue). CN’717 teaches that when P3 generation, i.e. Pn wherein n>2, subpluripotent stem cells are harvested, discarding the supernatant and the resulting pellet is added with a cryopreservation solution to the pellet, and the resuspended cells in cryopreservation solution is added to a cryopreservation tube, and the tube is placed in the programmed cooling device and then put it into a liquid nitrogen tank (p.4, step (6) Storage).
It would have been obvious to a person skilled in the art to cryopreserve the harvested P3 MSCs derived from decidua vera taught by CN’363 by using the cryopreservation process taught by CN’521 and CN’717 with a reasonable expectation of success. One skilled in the art would recognize that the cryopreservation procedure useful for decidua vera tissue taught by CN’521 or CN’717 would be suitable for the MSCs derived from the same tissue taught by CN’363. The combined teachings of CN’363 in view of CN’521 and CN’717 would also meet the limitation of claim 13 directed to Pn being P3.
Regarding the selective medium being a serum-free DMEM comprising 8-12% serum substitute, 0.5-1 mmol/ml of L-glutamine, 18-25 ng/ml of bFGF, 16-22 ng/ml of EGF, and 6-12 ng/ml of SCF, while CN’363 teaches serum-free medium, however, it does not teach the detailed composition.
CN’521 teaches the use of bFGF at 10-20 ng/ml, EGF at 10-20 ng/ml, SCF at 5-10 ng/ml, L-glutamine at 1-5 mmol/mL in the clinical-grade serum-free medium (p.3, 10th para.).
CN’748 teach the medium for parietal decidua mesenchymal stem cells is formed by basic medium and 10% serum substitute (p.3, 4th para. from the bottom), i.e. serum-free DMEM.
It would have been obvious to a person skilled in the art to replace the serum-free medium taught by CN’521 for the serum-free serum of CN’363 for the same purpose of culturing mesenchymal stem cells derived from placenta decidua vera, or parietal decidua (see above) with a reasonable expectation of success. As it is taught by CN’748 that 10% serum substitute is utilized in serum-free DMEM for parietal decidua MSCs, it would have been obvious to use 10% serum substitute in the serum-free DMEM taught by CN’521 replacing the serum-free medium of CN’363.
Regarding the limitation in claim 6 which is incorporated from the cancelled claim 9 directed to the step (2), CN’363 does not teach the limitation.
While CN’748 teach the digestion at 37°C for 1 hr. at constant temperature oscillation and post-digestive parietal decidua being filtered (see p.1, claim 1), however, the cited references do not particularly teach other limitations. However, it would have been obvious to a person skilled in the art to adjust the parameters of the constant temperature oscillation, taught by CN’748 for the method of CN’363 with a reasonable expectation of success. As the digestion condition including temperature, duration, oscillation speed, etc. is considered as result-effective parameters, the adjustment of particular conventional working conditions (e.g., concentration) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan having the cited reference before him/her.
Furthermore, CN’717 teach that the cleaned parietal decidua into 0.1-1cm3 pieces with sterile straight scissors, add an equal volume of tissue digestion solution preheated to 37°C, mix well, and place a constant temperature shaker at 37°C for 2 hours at a speed of 200 r/min (p.4, Example 1, step (2)).
It would have been obvious to a person skilled in the art to use the step of shaking to digest the parietal decidua taught by CN’717 for the method of CN’363 with a reasonable expectation of success as one skilled in the art would recognize that the step involving shaking (oscillation) the tissue for digestion can be used for the same purpose for the method steps taught by CN’363.
For the terminating the digestion with a selective medium at 3-6x volume of the digestion solution (RE: step (2)), CN’363 teaches the step of terminating the digestion with H-DMEM (p.3, Step (5)). Regarding the volume of the medium being 3-6x, CN’363 teach that 5 ml of the tissue digestion liquid is used and then 20 ml of H-DMEM is added (p.4, steps 3 and 4), and this teaching would meet the limitation.
For filtering using a filter screen with a pore size of 100 mm and centrifuging step for 5-7 min at 1,200-1,400 rpm (RE: step (2)), CN’363 teach the use of 100 mm of strainers (i.e. filter screen) after the digestion being terminated to remove the tissue block that is not digested, and centrifuged at 1000 r/min for 5 min. (p.4, step 4). While CN’363 does not particularly teach the range of the centrifugation speed, i.e. 1200-1400 rpm, however, the adjustment of particular conventional working conditions (e.g., centrifugation speed) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan having the cited reference before him/her.
Regrading claim 10 directed to step (5), CN’363 do not teach the surface of the cells being washed at least 2 times with PBS, the cells being digested with a cell digestion solution for 3-6 min and then the digestion being terminated with the selective medium. This step is directed to the step of harvesting adherent cells (i.e. mesenchymal stem cells) after cultivation. However, it is extremely well known in the art that the MSCs are cultured as adherent culture and they are harvested from the culture plate upon the digestion with a cell digestion solution. CN’717 teach that when the subpluripotent stem cells are reached 80-90% of fusion degree (confluency), the culture solution (culture medium) is completely discarded, washed, digested by adding the digestive solution, centrifuged (p.3, 9th para.). CN’717 also disclose that washing with PBS for 1-3 times, and digestion solution for 1-10 minutes, add complete culture solution to terminate digestion, and centrifuge at 500-1000 rpm for 5-7 min (p.3, 10th para.).
Regarding the resulting mixture being filtered through a filter screen with a pore size of 100 mm and a filtrate being centrifuged for 5-7 min. at 1,200-1,400 rpm of step (5), CN’363 in view of CN’717 do not particularly teach the limitation. However, it would have been obvious to a person skilled in the art to filter the dissociated cells after cell digestion to remove any undesired cell aggregates as the use of filter in the step after digesting the tissue as discussed above. The step of centrifuging is taught by CN’717 as discussed above. However, CN’717 does not teach the claimed centrifugal speed. However, the adjustment of particular conventional working conditions (e.g., centrifugation speed) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan having the cited reference before him/her.
Regarding claim 11 directed to the cell digestion solution comprising trypsin and EDTA as claimed, CN’363 do not teach the limitation. CN’717 (p.4) teach the digestive solution comprising trypsin with a mass percentage of 0.2-0.3% and EDTA at 0.003-0.005% (p.3, 11th para.).
It would have been obvious to use the digestion solution of CN’717 for the method of CN’363 for the same purpose with a reasonable expectation of success.
Regarding the concentration of trypsin being 0.1-0.15%, the cited references do not teach the limitation. However, in the absence of any evidence for the criticality of the concentration of EDTA as claimed, it is considered that a person skilled in the art would modify the concentration of EDTA in order to obtain a desired outcome of the cell dissociation for subculturing with a reasonable expectation of success. The adjustment of particular conventional working conditions (e.g., concentration) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan having the cited reference before him/her.
Furthermore, it is noted that CN’748 teach the concentration of trypsinase (i.e. trypsin) is 0.125% (p.3). It is noted that trypsinase disclosed in CN’748 appears to refer to trypsin.
Regarding claim 12 directed to the surface marker assay of CD73, CD90 and CD105 being more than 99% positive indexes, CN’363 do not teach the limitation. However, CN’521 teach that MSCs having surface marker expression of CD90, CD73 and CD105 being over 99% are obtained and such positive cell rates conforming the characteristics of MSCs (p.5, Flow Cytometry). It would have been obvious to a person skilled in the art to analyze the MSC cells subcultured in the method of CN’363 using the flow cytometry to determine the positive index of CD73, CD90 and CD105 to confirm that the MSC population is pure population. The same surface marker analysis is also taught by CN’748 (p.5, Step 6).
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.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN’363 in view of CN’521, CN’748 and CN’717 as applied to claim 6 above, and further in view of Abumaree et al. (of record)
Regarding claim 8 directed to the tissue cleaning solution comprising penicillin, streptomycin, RBC lysis buffer and normal saline (NS) and the claimed concentrations, CN’363 in view of CN’521, CN’748 and CN’717 do not teach the limitation.
With regard to the tissue cleaning solution, while CN’363 teach the step of cleaning the tissue, they do not teach the components of the solution.
For penicillin, streptomycin and RBC lysis buffer, it is extremely well known in the art that antibiotics for animal cells include penicillin-streptomycin mixture (aka pen-strep) according to Abumaree et al. Abumaree et al. further teach that the decidua parietalis tissue is separated from the placenta and washed with PBS to remove excess blood and minced, centrifuged to remove the supernatant, and red blood cells were lysed using red blood cell lysing buffer (see p.2, Materials and Methods). CN’521 also teach the use of penicillin and/or streptomycin (p.3, step (6)).
It would have been obvious to a person skilled in the art to use penicillin, streptomycin and RBC lysis buffer taught by Abumaree et al. for the method of CN’363 with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because the use of pen-strep and RBC lysis buffer is known in the art for the isolation of MSCs from placenta decidua parietalis according to Abumaree et al.
Abumaree et al. do not teach the use of normal saline, however, normal saline is well known in the art for washing placenta tissue according to CN’521 (p.1, Claim 1; p.3, step (2)). It is also noted that normal saline is known as 0.9% sodium chloride solution, and this would meet the limitation directed to the NS having a mass fraction of 0.8% to 1%.
Regarding the claimed concentrations of the ingredients of the tissue cleaning solution, while the cited references do not particularly disclose the concentration, however, the concentrations of these components are readily modified by routine optimization process. For instant case, the claimed cleaning solution is viewed as 1:1 mixture of RBC lysis buffer and NS, i.e. about 50% each, with about 1% of pen-strep. The concentration of the RBC lysis buffer in the final solution would be determined by the starting concentration of the buffer. As RBC lysis buffer is commercially available as a concentrate, e.g. 2x or 10x, the volume percentage of the RBC lysis buffer in NS would be determined accordingly. When 2x concentrate is used, the solution would have 50% of the RBC lysis buffer as claimed.
Furthermore, the adjustment of particular conventional working conditions (e.g., concentration) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan having the cited reference before him/her.
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.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN’363 in view of CN’521, CN’748, and CN’717 as applied to claim 6 above, and further in view of CN105340877A (published on 2/24/2016; CN’877 hereinafter; English translation attached).
Regarding claim 14 directed to the use of a cryopreservation liquid in a serum-free complete medium at 18-25%, and the cryopreservation liquid comprising DMSO at 55 g/100 ml and dextran 40 at 5 g/100 ml, the cited references do not teach the limitation.
CN’877 teach the use of Cryosure-DEX40 freezing solution for cryopreserving various cells including mesenchymal stem cells (p.1 claim 1; p.4, #3). CN’877 also teach the concentration of Cryosure-DEX40 in the cryoprotectant solution is 1 part along with 4 parts of human serum albumin (i.e. HAS:CryoSure-DEX40 = 4:1) (p.6, #4). The ratio of 4:1 taught by CN’877 can be converted to 20% CryoSure-DEX40 in the cryopreservation solution, and thus meet the claimed range of 18-25%. Regarding the cell density, CN’877 teach that the density of MSC is 1.25x106 cells/ml to 7.5x106 cells/ml (p.4, #4). This teaching would meet the range of 1.5-2.5x106 cells/ml.
It would have been obvious to a person skilled in the art to combine the teaching of CN’877 directed to the use of CryoSure-DEX40 for cryopreserving MSCs in order to cryopreserve the MSCs derived from placenta decidua tissue obtained by the method of CN’363 in view of CN’748, CN’521, and CN’717 with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because one skilled in the art would recognize that the teaching of CN’877, i.e. use of CryoSure-DEX40 and the MSC density for the cryopreservation would be one suitable options known in the art for the cryopreserving the MSCs of CN’363.
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 have been considered but are moot because the new ground of rejection due to the instant amendment.
Regarding the argument to the claim rejection under 35 U.S.C. 112(b), while some of the arguments along with the instant amendment overcame the rejections, however, there are still remaining issues as discussed above. Particularly, applicant alleged “high-glucose DMEM” is well-recognized and standardized technical term and one skilled in the art understands what this term intends to point out. The Examiner respectfully disagrees with the argument. While it is generally known what it means, however, it does not particularly define the meaning of the relative term, and it is merely a name and thus, there is no criteria what amount of glucose is excluded or included for “high” glucose in DMEM.
Regarding the term “SCGF”, this term is not understood to indicate “SCF” in the art. As the full name being “stem cell growth factor”, and the scope of the stem cell growth factor would be any known growth factor beneficial to stem cells, it is the Examiner’s position that this term does not necessarily point out SCF. Thus, the rejection is maintained.
The claim rejections under 35 USC 103 have been withdrawn due to the instant amendment. Particularly, the 103 rejection based on CN’717 in view of CN’363, CN’748 and CN’228, the priority date was redetermined upon the instant amendment, and thus, the CN’228 has been disqualified as a prior art. Thus, the arguments directed to this withdrawn rejection are moot.
It is noted that the claim rejection based on CN’363 in view of CN’521, CN’748, Abumaree et al. and Nestler et al. (claims 6 and 8-13) and further in view of CN’877 (claim 14) has been withdrawn and replaced with a new claim rejection as presented above. This is due to the instant amendment.
Applicant alleged that the CN’363 aim to solve completely different technical problems, and it is to “differentiate” placental MSCs into endometrial epithelial cells. The Examiner respectfully disagrees with this allegation. The claimed method is directed to prepare the MSCs from parietal decidua, and CN’363 teaches the method of isolating these MSCs from the same source regardless how they use the isolated cells. The claimed method involves essentially the same process of isolating these cells from a placental tissue along with parameters optimizable by routine experimentations, and these modifications are either taught by the cited secondary references or well known in the art for that matter.
It is also noted that the newly presented 103 rejection is combined with the teachings from CN’717 in order to address the new limitation directed to the trypsin-EDTA in the step (2).
Applicant’s arguments are mostly directed to the differences in the parameters in the claimed steps from the cited references, and the specific combination of parameters solves the technical problem identified in the background of the present application. The examiner considers the claimed specific parameters for digestion, subculturing involving washing, digesting, filtering, centrifuging, etc. as a part of routine optimization. The claimed steps are known in the art and the specific parameters for the known steps in order to prepare MSCs from a tissue source are within the purview of a person skilled in the art, and thus, it would have been obvious to a person skilled in the art to modify the parameters by routine experimentations, particularly in the absence of any criticality or unexpected results.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631