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
Acknowledgement is made of Applicants’ claim for foreign priority under 35 USC 119(b) to Taiwanese Application TW111104802, filed 09 February 2022. Receipt is acknowledged of certified copies of papers, in a non-English language, required by 37 CFR 1.55. Thus, the earliest possible priority for the instant application is 09 February 2022.
Claim Objections
Claim 10 is objected to because of the following informalities:
Regarding claim 10: The instant claim recites the limitation, “wherein the cell is selected from the group consisting of stem cell, … and epidermal cell.” Since the recitation of “the cell” is singular, Applicant must insert an article before each cell type such that the limitation reads, “wherein the cell is selected from the group consisting of a stem cell, … and an epidermal cell.”
Appropriate correction is required.
Claim Interpretation
Claim 5 further limits the polymer blended layer as being “prepared by mixing solutions of the pH-responsive polymer and nylon uniformly, coating onto the inner surface of the container, and drying it.” This is a product-by-process limitation. Product-by-process limitations are only considered in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the method of blending the polymers and applying the blend to the culture container imparts any particular structure or significance to the polymer blended layer, beyond the fact that the layer must comprise the combined pH-resistant polymer and nylon on the inner surface of the culture container. Thus, the claim will be interpreted as if the addition of a pH-resistant/nylon blend to an inner surface of the culture container fulfills the limitation detailed in the instant claim.
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 8-10 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 8: The instant claim recites the limitation, “wherein Step (2) and Step (3) are performed repeatedly.” In the instant case, it is unclear whether the claimed method requires repeating the steps in a step-wise order (2-3, 2-3, 2-3), or whether a step is repeated individually before performing the next step (2-2-2, followed by 3-3-3). Therefore, the metes and bounds of the claim cannot be determined, thus rendering the scope of the claim indefinite.
Appropriate correction is required.
Regarding claim 9: The instant claim recites the limitation, “wherein Step (2) and Step (3) may be performed repeatedly more than 3 times” (emphasis added). In the instant case, it is unclear if the phrase “may be” is treated as a hypothetical method step or is instead required. It is also unclear whether the claimed method requires repeating the steps in a step-wise order (2-3, 2-3, 2-3), or whether a step is repeated individually before performing the next step (2-2-2, followed by 3-3-3). Therefore, the metes and bounds of the claim cannot be determined, thus rendering the scope of the claim indefinite.
Appropriate correction is required.
Regarding claim 10: The instant claim recites the limitation, “wherein the cell is selected from the group consisting of stem cell, preferably adipose-derived stem cell, mesenchymal stem cell or skin stem cell; fibroblast cell, preferably foreskin fibroblast or embryonic fibroblast; epithelial cell, preferably proximal renal tubular epithelial cell; cancer cell, preferably epithelial lung cancer cell;…”. In the instant case, the term “preferably” is being treated as exemplary language. Therefore, the exemplary term “preferably” renders the instant claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Appropriate correction is required.
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 1-6 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Wagner et al (US 2023/0065504 A1) in view of Lin et al (Biomaterials, 2006).
Wagner et al is considered prior art under 35 USC 102(a)(2), with an effective filing date of 29 September 2021. Lin et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 1-4: Wagner et al disclose platforms, systems, and methods including a cell culture system for the continuous and automated culture of cells (Abstract; Paragraphs [0008], [0676], [0828]-[0829]).
As such, Wagner et al disclose that the cell culture systems comprise cell culture containers that are coated on the interior surface with polymeric layers – including thermoplastic polymers – that allow for the adherence of the cells to the layer (Paragraphs [0543], [0545]-[0546], [0656], [0663], [0703], [0773], [0788], [0816]).
Wagner et al further disclose that the cultured cells can be epithelial cells, epidermal cells, or melanocytes (Paragraphs [0024], [0191], [0200]).
Wagner et al do not disclose that the polymeric layer comprises a blend of a pH-resistant polymer – such as chitosan – and nylon, as required by instant claim 1.
Lin et al, however, disclose the effects of chitosan/nylon-blended membranes on melanocytes (Abstract).
As such, Lin et al disclose a chitosan/nylon-blended membrane comprising either 25%, 50%, or 75% chitosan – termed NC25, NC50, and NC75 respectively – wherein the adhesion of the melanocytes is enhanced within the increase in nylon content (Page 5080, 2.1 Membrane preparation and characterization; Pages 5082-5083, 3.4 Cell morphology & 3.5 Cell adhesion and cell growth; Figure 5). Lin et al further disclose that the melanocyte cell growth was highest when cultured on the NC50 membrane (Page 5083, 3.5 Cell adhesion and cell growth).
Therefore, it would have been prima facie obvious to have modified the polymeric layer within the cell culture container of Wagner et al to be the NC50 layer of Lin et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to coat the cell culture container with a polymeric blend that enhances melanocyte adherence without hindering cell growth, and would have had a reasonable expectation of success given that the disclosures of Wagner et al and Lin et al are both concerned with the culture and adherence of melanocytes to a polymeric coating. See MPEP § 2143(I)(G).
Consequently, Wagner et al as modified by Lin et al render obvious the continuous culture of melanocytes (claim 2), wherein the melanocytes are cultured within a cell culture container comprising a 1:1 (claim 4) blended layer of chitosan (claim 3) and nylon – or 50% chitosan and 50% nylon – on the inner surface of the cell culture container. This therefore renders obvious the system of instant claim 1.
Regarding claim 5: The instant claim comprises a product-by-process limitation that is interpreted as set forth above.
Accordingly, as the cell culture container rendered obvious by Wagner et al as modified by Lin et al comprises a layer of chitosan blended with nylon, this therefore renders obvious the system of instant claim 5 for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 6: Following the discussion of claim 1, Lin et al further disclose that the NC50 chitosan-nylon layer comprises regions a plurality of nylon regions within the chitosan membrane (Page 5081, 3.3 Characterization of the membranes; Figure 3C). This therefore renders obvious the system of instant claim 6 for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 10: Following the discussion of claim 1, Lin et al further disclose that the cultured cells are epithelial cells, epidermal cells, or melanocytes (Paragraphs [0024], [0191], [0200]). This therefore reads on the system of the instant claim.
Claims 1- 10 are rejected under 35 U.S.C. 103 as being unpatentable over Wagner et al (US 2023/0065504 A1) in view of Lin et al (Biomaterials, 2006) and further in view of Chen et al (Biomaterials, 2012).
The discussion of Wagner et al as modified by Lin et al regarding claims 1-2 can be observed above and are relied upon herein, the content of which is incorporated in its entirety. Wagner et al as modified by Lin et al render obvious claims 1-6 and 10. Chen et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 7: As aforementioned in the discussion of claim 2 above, Wagner et al as modified by Lin et al render obvious the continuous culture of melanocytes, wherein the melanocytes are cultured within a cell culture container comprising a 1:1 blended layer of chitosan and nylon on the inner surface of the cell culture container.
Wagner et al further disclose that the cell culture system can comprise a pH sensor, and that the computing subsystem comprised within the cell culture system can adjust the pH of the culture medium comprised within the cell culture container (Paragraphs [0019], [0198], [0203], [0467], [0534], [0557], [0582], [0597], [0810]).
The combination of Wagner et al and Lin et al fail to teach that the medium of the cell culture medium is controlled to a pH value of 6.9-7.4 to cultivate the cells and raised to a pH value of 7.5-8.5 to detach the cells, as required by instant claim 7.
Chen et al, however, disclose that chitosan is a pH-responsive polymer that allows for the attachment of epidermal keratinocytes at a pH of 7.2, and the detachment of cells at a pH of 7.65 (Page 1337, 2.5 Cell culture; Pages 1338-1339, 3. Results; Pages 1340-1341; Figures 2, 6).
Chen et al further disclose that cells are able to re-attach onto the chitosan surface and proliferate after reducing the pH of the culture medium back down to 7.2 (Page 1339; Figure 6C).
Therefore, it would have been prima facie obvious to have modified the continuous cell culture method of Wagner et al in view of Lin et al such that the epidermal melanocytes seeded onto the chitosan-nylon layer are cultured within the cell culture container in a culture medium having a pH of 7.2, and then allowed to detach from the chitosan-containing layer by raising the pH of the culture medium to a pH of 7.65, as detailed in Chen et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to have a means of simply detaching the epidermal cells without having to utilize enzymatic treatment or otherwise disrupting the viability of the cells (Chen et al, Pages 1340-1341), and would have had a reasonable expectation of success since the cell culture system of Wagner et al is configured with the means for monitoring and adjusting the pH of the cell culture medium. See MPEP § 2143(I)(G).
Consequently, Wagner et al as modified by Lin et al and Chen et al render obvious a method of continuously culturing epidermal melanocytes, wherein the melanocytes are cultured within a cell culture container comprising a blended layer of chitosan and nylon on the inner surface of the container, and wherein the melanocytes are maintained in a culture medium having a pH of 7.2 and detached from the chitosan-containing layer by raising the pH of the culture medium to 7.65. This therefore renders obvious the method of the instant claim.
Regarding claims 8-9: Following the discussion of claim 7, Wagner et al further disclose that the continuous cell culture process may be performed wherein a fraction of the cells are continuously harvested from the cell culture system (Paragraphs [0446], [0829]).
This therefore renders obvious the method of the instant claims, as the ordinary artisan would recognize that the “continuous harvesting” of the “fraction of cells” indicates that the culturing and detachment of the cells is repeatedly occurring. Furthermore, one of ordinary skill in the art before the effective filing date of the invention would have been motivated to repeatedly detach and reattach – or passage – the portion of cells such that the cell growth does not overwhelm the cell culture container, and would have had a reasonable expectation of success since the disclosure of Chen et al teaches that the cells can be detached and reattached to the chitosan layer without impacting the viability or proliferation potential of the cells (Chen et al, Pages 1340-1341). See MPEP § 2143(I)(G).
Consequently, Wagner et al as modified by Lin et al and Chen et al render obvious a method of continuously culturing epidermal melanocytes, wherein the cultivation and detachment steps via the adjustment of the culture medium pH are performed repeatedly (claim 8), and can be performed more than three times (claim 9). This therefore renders obvious the method of the instant claims.
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).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633