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 1-17 and 21-23) in the reply filed on 8/3/2026 is acknowledged.
Claims 18-20 and 24 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-17 and 21-23 have been considered on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claims 5 and 15 are objected to because of the following informalities: the wherein clause of claim 5 would be more appropriate as “wherein the nanofiber is composed of water-insoluble polysaccharides and added to the medium..” Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-8 and 10-17 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.
The instant claims disclose “adherent cell” without further limiting what type of cells. Thus the scope of “adherent cell” is extremely broad not only including mammalian cells but also any other known cells that can adhere to any material. While claim 9 discloses mammalian cell types, however, claim 1 and its dependent claims do not particularly require type of cells as long as they are adherent.
The term “adherent” is not particularly limited to the subject/material to which the cells be attached.
Many mammalian cells are known to be adherent to a culture surface or other cells. It is also known that plant cells are adherent to each other or artificial fibrous scaffolds (Calcutt et al. 2021, Science Advances), and it is acknowledged that the instant specification discloses plant cells. It is also known that yeast cells are adherent to other cells or substrates (see Willaert, 2018, J. Fungi).
As the claimed term does not limit the type of adherent cells, the scope of this term would encompass not only mammalian adherent cells but also non-mammalian cells such as yeast that are adherent.
The instant specification does not provide written description for the entire scope of the claimed invention as it discloses only mammalian adherent cells.
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus…when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.”
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 2, 8 and 12 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 2 and 12 recites the limitation "the system" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of extracellular matrix is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: while the most species listed in claim 8 are known to be ECM but “RGD sequences” is not considered as ECM.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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) 1-2, 5, 7, 9, 11-12, and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hayashi et al. (US2017/0009201A1; IDS ref.)
Regarding claims 1-2, 7 and 9, Hayashi et al. teach a method of culturing mammalian cells including mesenchymal stem cells (para. 78; Example 25) in suspension in a culture medium comprising nanofibers such as cellulose, chitosan or chitin (para. 33; Experimental Example 18).
Hayashi et al. teach that after mixing the cells and the culture composition to a uniform dispersion using instrument such as stirrer, the culture medium may be rotated, shaken or stirred as necessary (para. 188). The stirring taught by Hayashi et al. would meet the limitation of claim 2 as the stirring would have the nanofiber and cells in suspension move continuously by the force generated by stirring (external force).
Regarding claims 5 and 15 directed to the concentration of the water-insoluble polysaccharides, Hayashi et al. teach the concentration of the chitin nanofiber in the medium is not less than 0.0001%, 0.001% up to 0.03% (w/v) (para. 304).
Regarding claims 11-12, the steps of the method are taught by Hayashi et al. as discussed above. For the intended purpose/result of producing a sphere of adherent cells with a uniform sphere size, while Hayashi et al. teach the formation of spheres with uniform size (para. 176). Furthermore, the intended purpose or result as claimed does not provide any additional active step required by the claimed method. Rather, the results are determined by the claimed method steps. As Hayashi et al. teach the identical steps as claimed, the results of the method taught by Hayashi et al. would be inherently the same as the claimed method.
Thus, the reference anticipates the claimed invention.
Claim(s) 1-2, 5, 7, 9, 11-12, 15 and 21-23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kanaki et al. (US2020/0040304A1; IDS ref.).
Regarding claims 1-2, 7 and 9, Kanaki et al. teach a method of culturing adherent cells in suspension with a culture medium comprising water-insoluble nanofibers including cellulose, chitin or chitosan (Abstract; paras. 13, 33, 41, 166). Kanaki et al. teach that the adherent cells include mesenchymal stem cell (para. 10-11). Kanaki et al. teach the obtained cell suspension is cultured with rotation, shaking or stirring as necessary (para. 70). The stirring taught by Kanaki et al. would meet the limitation of claim 2 as the stirring would have the nanofiber and cells in suspension move continuously by the force generated by stirring (external force).
Regarding claims 5 and 15 directed to the concentration of the water-insoluble polysaccharides, Kanaki et al. teach the concentration of the chitin nanofiber in the medium is not less than 0.0001% (w/v) and not more than 1.0% (w/v) (para. 57). This would overlap with the claimed range.
Regarding claims 11-12, the steps of the method are taught by Kanaki et al. as discussed above. For the intended purpose/result of producing a sphere of adherent cells with a uniform sphere size, Kanaki et al. do not particularly teach the limitation. However, the intended purpose or result as claimed is determined by the claimed method steps. As Kanaki et al. teach the identical steps as claimed, the results of the method taught by Kanaki et al. would be inherently the same as the claimed method.
Regarding claims 21-22 directed to the method for enhancing production of an extracellular vesicle of a mesenchymal stem cell or producing a mesenchymal stem cell in which production of an extracellular vesicle being enhanced, Kanaki et al. exemplify a method of suspension culturing mesenchymal stem cells attached to chitosan nanofiber (para. 99). While Kanaki et al. do not particularly teach the result of “enhancing production of an extracellular vesicle”, however, this effect/result is inherent because the method steps of Kanaki et al. are identical to the claimed invention.
M.P.E.P. §2112 states that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). >In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” Therefore, a holding of anticipation is clearly required.
Regarding to claim 23, the limitation directed to the extracellular vesicle being exosomes, the production of extracellular vesicle from mesenchymal stem cells is inherent property of the cells, and the extracellular vesicle inherently contain exosomes. As this limitation does not require any additional active step to be performed other than those listed in claim 21, thus, this limitation does not provide any patentable weight in determining patentability of the claimed method.
Thus, the reference anticipates the claimed invention.
Claim Rejections - 35 USC § 103
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) 1-2, 4-12, 14-17 and 21-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hayashi et al. (supra)
Regarding claims 1-2, 5, 7, 9, 11-12, and 15, as discussed above, Hayashi et al. anticipate the subject matter of the claims, and thus, render them obvious.
Regarding claims 4 and 14 directed to the stirring being performed constantly during the culture, it would have been obvious to a person skilled in the art that the method of culturing adherent cells in suspension taught by Kanaki et al. requires constant stirring in order to maintain a suspension culture.
Regarding claims 6 and 8 directed to the nanofiber carrying an extracellular matrix, Kanaki et al. teach that the mixing step of water-insoluble polysaccharides and the culture composition (i.e. medium composition) to have a uniform dispersion (para.53 and 70). Kanaki et al. also teach additional molecules including various extracellular matrices (para. 59). It would have been obvious to a person skilled in the art to arrive the nanofiber carrying extracellular matrix when the medium composition comprising the extracellular matrices and the nanofiber are mixed into a uniform dispersion. This is because the instant specification discloses that the nanofiber carrying ECM is prepared by mixing them (para. 102).
Regarding claim 10, as Kanaki et al. teach various nanofibers composed of cellulose, chitin or chitosan, it would have been obvious to use chitosan fiber along with other nanofiber for the method of Kanaki et al. for the same purpose.
Regarding claims 21-22 directed to the method for enhancing production of an extracellular vesicle of a mesenchymal stem cell or producing a mesenchymal stem cell in which production of an extracellular vesicle being enhanced, while Hayashi et al. teach mesenchymal stem cells being one of adherent cells (para. 78), Hayashi et al. do not particularly teach the result of “enhancing production of an extracellular vesicle”. However, it would have been obvious to a person skilled in the art to use the method of Hayashi et al. for culturing mesenchymal stem cells, and this effect/result of the method would be inherently the same as the claimed invention because the method steps of Hayashi et al. are identical to the claimed invention.
M.P.E.P. §2112 states that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). >In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” Therefore, a holding of anticipation is clearly required.
Regarding claim 16, Hayashi et al. teach cell strainers having a mesh size of 40 μm to trap the spheres on the filter (para. 259). Thus, it would have been obvious to a person skilled in the art to isolate spheres formed by the method of Hayashi et al. using a cell strainer.
Regarding claim 17, Hayashi et al. teach the harvested spheres were treated with trypsin-EDTA to dissociate the spheres (para. 259). This teaching is considered to meet the limitation of claim 17.
Regarding to claim 23, the limitation directed to the extracellular vesicle being exosomes, the production of extracellular vesicle from mesenchymal stem cells is inherent property of the cells, and the extracellular vesicle inherently contain exosomes. As this limitation does not require any additional active step to be performed other than those listed in claim 21, thus, this limitation does not provide any patentable weight in determining patentability of the claimed method.
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) 1-2, 4-12, 14-15 and 21-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kanaki et al. (supra)
Regarding claims 1-2, 5, 7, 9, 11-12, 15 and 21-23, as discussed above, Kanaki et al. anticipate the subject matter of the claims, and thus, render them obvious.
Regarding claims 4 and 14 directed to the stirring being performed constantly during the culture, it would have been obvious to a person skilled in the art that the method of culturing adherent cells in suspension taught by Kanaki et al. requires constant stirring in order to maintain a suspension culture.
Regarding claims 6 and 8 directed to the nanofiber carrying an extracellular matrix, Kanaki et al. teach that the mixing step of water-insoluble polysaccharides and the culture composition (i.e. medium composition) to have a uniform dispersion (para.53 and 70). Kanaki et al. also teach additional molecules including various extracellular matrices (para. 59). It would have been obvious to a person skilled in the art to arrive the nanofiber carrying extracellular matrix when the medium composition comprising the extracellular matrices and the nanofiber are mixed into a uniform dispersion. This is because the instant specification discloses that the nanofiber carrying ECM is prepared by mixing them (para. 102).
Regarding claim 10, as Kanaki et al. teach various nanofibers composed of cellulose, chitin or chitosan, it would have been obvious to use chitosan fiber along with other nanofiber for the method of Kanaki et al. for the same purpose.
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) 3 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hayashi et al. (supra) or Kanaki et al. (supra) as applied to claims 1 and 22 above, in further view of Olmer et al. (2012, Tissue Engineering: Part C) and Millipore (2016, Scalability of the Mobius Single-use Bioreactors).
Regarding claim 3 directed to the stirring being performed by a means accompanying a blade and a rotation speed of 0.01 to 50 m/min, Hayashi et al. or Kanaki et al. do not teach the limitation.
As discussed above, the method of Hayashi et al. or Kanaki et al. utilizes stirring during the culturing step, and it is well known in the art that suspension culture with constant stirring is carried out using stirred bioreactors (Olmer et al.).
Regarding the rotation speed being a tip speed as claimed, Millipore teaches that tip speed of the impeller of stir bioreactors is one of several parameters for culturing CHO cells in suspension culture (Abstract), and it teaches testing various tip speeds including 0.3 m/s (i.e. 18 m/min) up to 1.5 m/s based on the scale of the bioreactors (Table 2). Thus, it would have been obvious to a person skilled in the art to modify the tip speed of the impeller of the stir bioreactors for the method of Hayashi et al. or Kanaki et al. culturing adherent cells in suspension along with the water insoluble polysaccharide nanofibers 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.
Claim(s) 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kanaki et al. (supra) as applied to claim 11 above, in view of Hayashi et al. (supra)
Regarding claim 16 directed to the method of isolating spheres produced by the method of claim 11 to a cell strainer, Kanaki et al. do not particularly teach the limitation.
Hayashi et al. teach the method substantially similar to the method of Kanaki et al. (see above). Thus, the method of Kanaki et al. would result in the formation of cell spheres as taught by Hayashi et al.
Regarding claim 16, Hayashi et al. teach cell strainers having a mesh size of 40 μm to trap the spheres on the filter to isolate/harvest the spheres, and the harvested spheres were treated with trypsin-EDTA (para. 259). (para. 259).
Thus, it would have been obvious to a person skilled in the art to isolate spheres formed by the method of Kanaki et al. using a cell strainer taught by Hayashi et al. and then treat the isolated spheres with Trypsin-EDTA as taught by Hayashi et al. with a reasonable expectation of success.
Regarding claim 17, the claimed first method step is taught by Kanaki et al. as they teach a method of suspension culturing adherent cells in a medium comprising water-insoluble polysaccharide nanofibers (see above). With regard to the second step, Kanaki et al. do not teach the limitation. However, as discussed above, Hayashi et al. teach cell strainers having a mesh size of 40 μm to trap the spheres on the filter to isolate/harvest the spheres, and the harvested spheres were treated with trypsin-EDTA (para. 259). Thus, it would have been obvious to a person skilled in the art to carry out the isolation of spheres and treatment with trypsin-EDTA as taught by Hayashi et al. after the method of Kanaki et al. is carried out.
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.
Conclusion
No claims are allowed.
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/TAEYOON KIM/ Primary Examiner, Art Unit 1631
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