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 .
Priority
The instant application is a divisional under 35 USC § 121 of US Application No. 17/275139, filed 10 March 2021 (which is now abandoned). Parent Application No. 17/275139 is a national stage entry under 35 USC 371 of PCT/JP2019/035651, filed 11 September 2019. Acknowledgement is made of Applicant’s claim for foreign priority under 35 USC 119(b) to Japanese application JP2018-170092, filed 11 September 2018. Receipt is acknowledged of certified copies of papers, in a non-English language, required by 37 CFR 1.55.
Status of the Claims
Applicant’s submission filed 22 November 2023 has been entered. Claims 1-14 are pending. Therefore, prosecution on the merits commences for claims 1-14.
Drawings
The replacement drawing sheets filed 08 January 2024 are acknowledged and entered into the application file.
Specification
The substitute Specification filed 08 January 2024 is acknowledged and entered into the application file.
Claim Objections
Claim 11 is objected to because of the following informalities:
Regarding claim 11: The instant claim is objected to for reciting “[t]he method according to claim 9, further comprising one or more chambers…” instead of “[t]he method according to claim 9, wherein the separation device further comprises
Furthermore, the instant claim is objected to for reciting “… have a smaller opening to suppress more the passage of the separation target”, which is grammatically incorrect. The Examiner suggests amending the limitation to instead recite “wherein… mesh-holes of a mesh structure for separation located higher have a smaller opening are to further suppress the passage of the separation target”, or the like.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-14 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.
Regarding claim 1: Instant claim 1 recites the limitation "the liquid" in Line 8. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “a liquid” within the claim language and it is not an inherent characteristic of the previously stated features. See MPEP § 2173.05(e).
Likewise, instant claim 1 recites the limitation “the suspension medium” in Line 8. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “a suspension medium” within the claim language and it is not an inherent characteristic of the previously stated features. See MPEP § 2173.05(e).
Instant claim 1 also recites the limitation “the advancing direction of the liquid in the aforementioned suspension” in Line 8. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “an advancing direction” within the claim language and it is not an inherent characteristic of “the liquid in the aforementioned suspension”. See MPEP § 2173.05(e).
Instant claims 2-14 are included in the rejection because they depend from parent claim 1.
Appropriate correction is required.
Regarding claim 3: Instant claim 3 recites the limitation “the liquid medium” in Line 2. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “a liquid medium” within the claim language. See MPEP § 2173.05(e). It is of note that “the liquid medium” does not necessarily refer to “the suspension medium”.
Instant claim 4 is included in the rejection because it depends from parent claim 3.
Appropriate correction is required.
Regarding claim 4: The instant claim recites the limitation “dog kidney renal tubule epithelial cell (MDCK cell)” in Lines 5-6. While parentheticals can be used as abbreviations, the use of parentheticals adjacent to terms which recite alternate names or isoforms renders the claim indefinite because it is not clear whether the items within the parentheticals are required or optional. In the instant case, the recitation of “MDCK cell” is not an obvious abbreviation for “dog kidney renal tubule epithelial cell”. Therefore, the scope of the claim is indefinite.
Appropriate correction is required.
Regarding claim 5: The instant claim recites the limitation “the liquid medium” in Line 2. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “a liquid medium” within the claim language. See MPEP § 2173.05(e). It is of note that “the liquid medium” does not necessarily refer to “the suspension medium”.
Appropriate correction is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 7-9, and 13-14 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Vincent et al (US 2016/0251628 A1, of record on IDS filed 19 July 2024).
Vincent et al disclose devices suitable for filtration including diafiltration of a suspension containing a species such as particles, cells or macromolecules, apparatus comprising such devices and methods of using the devices and apparatus (Abstract).
As such, Vincent et al disclose a method for filtering a first species from a second species in suspension, wherein the suspension comprising the first and second species is introduced through an inlet port into a first chamber of a filtration device, upwardly flowed through the first chamber and a mesh filter having mesh-holes of a defined size that only allow passage of the first species to a second chamber of the filtration device, such that the first species is collected within an reservoir connected to the second chamber and the second species is collected within a reservoir connected to the first chamber (Paragraphs [0060], [0065], [0068], [0164]-[0171], [0175]-[0178]; Figures 1, 3, 18). Vincent et al further disclose that the first species is mesenchymal stem cells, the second species is nanofibers, and the suspension is a liquid culture medium [0015]-[0017], [0019]-[0023]).
Vincent et al further disclose that the first chamber within the filtration device comprises two inlet ports on the side wall of the chamber, one for the suspension and one for a wash fluid, and an outlet port to a reservoir that collects the second species (Paragraphs [0175]-[0181]; Figure 3).
Vincent et al further disclose that the mesh filter within the filtration device is a planar mesh filter (Paragraphs [0026], [0252]).
Vincent et al further disclose that the second chamber of the filtration device is situated on top of the first chamber (Paragraphs [0175]-[0181]; Figure 3).
Accordingly, Vincent et al anticipate the claims as follows:
Regarding claims 1-3 and 13: Vincent et al disclose a method of separating a cellular species from a non-cellular species using a filtration device, wherein a suspension comprising mesenchymal stem cells and nanofibers suspended in liquid medium is introduced through an inlet port into a first chamber of the filtration device, upwardly flowed through the first chamber to a mesh filter having mesh-holes of a defined size that only allow passage of the mesenchymal stem cells to a second chamber of the filtration device (claims 2-3), such that the mesenchymal stem cells are collected within an reservoir connected to the second chamber (claim 13) and the nanofibers are collected within a reservoir connected to the first chamber. As the nanofiber is inherently a fine scaffold material, this therefore reads on the method of instant claim 1. See Paragraph [0027] of instant Specification filed 08 January 2024.
Regarding claim 7: Following the discussion of claim 1, Vincent et al further disclose that the mesh filter is planar. This therefore reads on the method of the instant claim, wherein the mesh structure for separation is sheet-like.
Regarding claim 8: Following the discussion of claim 1, Vincent et al further disclose that the first chamber within the filtration device comprises two inlet ports on the side wall of the chamber, one for the suspension and one for a wash fluid, and an outlet port to a reservoir that collects the nanofibers. This therefore reads on the method of the instant claim.
Regarding claim 9: Following the discussion of claim 1, Vincent et al further disclose that the second chamber is situated on top of the first chamber of the filtration device, and that the inlet ports are situated on the side wall of the first chamber. This therefore reads on the method of the instant claim.
Regarding claim 14: Following the discussion of claim 1 above, Vincent et al further disclose that the cross-sectional area of the filter is 10 cm2 for a 1.5 mL cell chamber volume (Paragraphs [0252], [0274]; Figure 21). Vincent et al further disclose that the suspension is introduced into the first chamber having a 1.5 mL cell chamber volume via the lower port at a flow rate of 2 mL/min (Paragraphs [0293]-[0294]). Therefore, the flow velocity of the suspension through the filter is 3 mm/s, which lies within the claimed range and reads on the method of the instant claim. See MPEP § 2131.03.
It is of note that the Examiner utilized the standard conversion of 1 mL = 1 cm3 in order to convert the flow rate of 2 mL/min to 2 cm3/min, and the following formula for flow velocity:
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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.
Claims 1-3, 5-10, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Vincent et al (US 2016/0251628 A1, of record on IDS filed 19 July 2024).
The discussion of Vincent et al regarding claims 1-2 and 9 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Vincent et al anticipate claims 1-3, 7-9, and 13-14.
Regarding claim 5: Following the discussion of claim 2 above, Vincent et al further disclose an embodiment of the invention wherein one species is a microcarrier – or nanofiber – and cell complex, and another species is proteins (Paragraph [0019]).
Vincent et al further disclose that the cells can be cells specialized for the secretion of hormones (Paragraph [0023]).
Vincent et al do not disclose the separation of hormones secreted by the cells from the nanofiber-cell complex, as required by instant claim 5.
Vincent et al do, however, disclose mesh filters having mesh-holes that are customizable to allow a first species to pass through while preventing a second species from passing (Paragraph [0015]-[0017], [0019]-[0020], [0025]).
Therefore, it would have been prima facie obvious to have modified the method of Vincent et al such that secreted hormones are separated from the nanofiber-cell complex. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to isolate the hormones released into the liquid medium from the nanofiber-cell complexes, as it allows for analysis of the cell secretome, and would have had a reasonable expectation of success given the tunable mesh filter of Vincent et al. See MPEP § 2143(I)(G).
Consequently, Vincent et al render obvious a method of separating the secreted hormones (reads on “humoral factor released from the cells into the liquid medium by suspension culture” – see Paragraphs [0047] of instant Specification filed 08 January 2024) from the nanofiber-cell complex (reads on “scaffold material to which adherent cells suspension-cultured in the liquid medium are attached”). This therefore renders obvious the method of the instant claim.
Regarding claim 6: Following the discussion of claim 2 above, Vincent et al further disclose an embodiment of the invention wherein one species is an intact cell and another species is lysed cell fragments (Paragraph [0017]).
Vincent et al do not disclose the separation of proteins released from the lysed cells and the lysed cell fragments, as required by instant claim 6.
Vincent et al do, however, disclose the separation of suspended proteins or nucleic acids, as well as a mesh filter having mesh-holes that are customizable to allow a first species to pass through while preventing a second species from passing (Paragraph [0015]-[0017], [0019]-[0020], [0025]).
Therefore, it would have been prima facie obvious to have modified the method of Vincent et al such that secreted proteins and nucleic acids from lysed cells are separated from the lysed cell fragments. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to isolate the cell lysate comprising proteins and nucleic acid from the deteriorated scaffolding or fragments of the lysed cells, as it allows for downstream analysis of the lysate, and would have had a reasonable expectation of success given the tunable mesh filter of Vincent et al. See MPEP § 2143(I)(G).
Consequently, Vincent et al render obvious a method of separating the cell lysate comprising proteins and nucleic acids (reads on “substance derived from the adherent cell and released into the liquid from the adherent cell”) from the lysed cell fragments or scaffolding (reads on “scaffold material left in the liquid by lysis of the cells”). This therefore renders obvious the method of the instant claim.
Regarding claim 10: Following the discussion of claim 9 above, Vincent et al reasonably suggest that the inlet port is situated on the side wall of the first chamber at a height that is greater than 40% of the chamber height, as the central axis appears to be at a height that is at least 50% of the side wall (Paragraph [0274]; Figures 16-17, 19-20). This therefore renders obvious the method of the instant claim. See MPEP § 2144.05.
Claims 1-10 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Vincent et al (US 2016/0251628 A1, of record on IDS filed 19 July 2024) in view of Hayashi et al (US 2017/0009201 A1, of record on IDS filed 22 November 2023).
The discussion of Vincent et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Vincent et al anticipate claims 1-3, 7-10, and 13-14. Vincent et al render obvious claims 1-3, 5-10, and 13-14. Hayashi et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 4: As aforementioned in the discussion of claim 3 above, Vincent et al disclose the separation of mesenchymal stem cells from nanofibers.
Vincent et al do not disclose that the nanofibers are composed of a water-insoluble polysaccharide, as required by instant claim 4.
Hayashi et al, however, disclose the suspension culture of mesenchymal stem cells with nanofiber scaffolding structures, wherein the nanofibers are comprised of chitin (Abstract; Paragraphs [0078], [0092], [0098], [0103], [0163]). It is of note that chitin is a water-insoluble polysaccharide (Paragraph [0103]).
Therefore, it would have been prima facie obvious to have substituted the nanofiber of Vincent et al with the chitin nanofiber of Hayashi et al. One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two nanofibers are functionally comparable, as they are both in suspension culture with mesenchymal stem cells, and thereby would have been able to substitute the nanofibers with predictable results. See MPEP § 2143(I)(B).
Consequently, Vincent et al as modified by Hayashi et al render obvious a method of separating mesenchymal stem cells from nanofiber scaffolds, wherein the nanofiber scaffolds are comprised of chitin. As chitin is inherently a water-insoluble polysaccharide, this therefore renders obvious the method of the instant claim.
Claims 1-3 and 5-14 are rejected under 35 U.S.C. 103 as being unpatentable over Vincent et al (US 2016/0251628 A1, of record on IDS filed 19 July 2024) in view of Yamanishi et al (US 2015/0079677 A1).
The discussion of Vincent et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Vincent et al anticipate claims 1-3, 7-10, and 13-14. Vincent et al render obvious claims 1-3, 5-10, and 13-14. Yamanishi et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 11-12: As aforementioned in the discussion of claim 9 above, Vincent et al disclose that the second chamber is situated on top of the first chamber of the filtration device.
Vincent et al do not disclose that the second chamber comprises at least a third chamber situated on top of it, wherein the second and third chamber are separated by a mesh filter having smaller mesh-holes compared to the mesh filter situated between the first and second chambers, as required by instant claim 11.
Yamanishi et al, however, disclose the filtration and enrichment of stem cells from a suspended stem cell mixture, wherein the stem cell suspension is introduced into a filtration device and passed through two filters having decreasing pore size, wherein the filters divide the filtration device into three separate subchambers (Paragraphs [0005], [0030]-[0031], [0075]-[0078], [0080], [0098]-[0099], [0114]-[0115], [0129]-[0131], [0137], [0144], [0176]-[0184], [0203], [0205], [0207]-[0209]; Figures 7-8).
Therefore, it would have been prima facie obvious to have modified the method of Vincent et al such that the filtration device comprised an additional filter with corresponding chamber on top of the second chamber, as suggested by Yamanishi et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to include the additional filter, as it further enriches the isolated stem cells within the suspension, and would have had a reasonable expectation of success given that the addition of a mesh filter within the filtration device of Vincent et al would not have been outside the skillset of the ordinary artisan, especially provided the disclosures of both Vincent et al and Yamanishi et al. See MPEP § 2143(I)(G).
Consequently, Vincent et al as modified by Yamanishi et al render obvious a method for separating mesenchymal stem cells from nanofiber scaffolds, wherein a suspension comprising mesenchymal stem cells and nanofibers suspended in liquid medium is introduced through an inlet port into a first chamber of the filtration device and upwardly flowed through the first chamber to a first mesh filter, a stacked second chamber, a second mesh filter, and a stacked third chamber (claim 12), wherein the first mesh filter and second mesh filter have mesh-holes of a defined size that only allow passage of the mesenchymal stem cells, and are smaller within the second mesh filter. This therefore renders obvious the method of instant claim 11.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633