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 .
Claim Status
1. The amendment filed 06/09/2025 has been entered. Claims 1-2, 4, 9, 11, 15, 44-46, 51, 58, 62, 90 and 124-129 are pending. Claims 6 – 7, 15, 18, 20, and 123 have been cancelled. New claims 126 – 129 have been added.
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1, 4, 6, 7, 9, 11, 15, 18, 20, 44, 45, 51, 58, 62, 123, and 124) in the reply filed on 01/14/2025 is acknowledged.
3. Claims 2, 46, 90, and 125 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/14/2025.
Priority
4. This application claims benefit to US Provisional application 62904490 filed 09/23/2019 and US Provisional application 62900184 filed 09/13/2019.
Claims Under Consideration
5. Claims 1, 4, 9, 11, 44, 45, 51, 58, 62, 124, and 126 – 129 are under consideration).
Withdrawn Claim Rejections
6. The rejection of claims 6, 7, 15, 18, 20, and 123 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 are rendered moot by Applicant’s cancellation of these claims.
7. The rejection of claims 1, 4, 9, 11, 44, 45, 51, 58, 62, and 124 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of Applicant’s amendment to the claims.
8. The rejection of claims 6, 7, and 123 under 35 U.S.C. 102(a)(2) is rendered moot by Applicant’s cancellation of these claims.
9. The rejection of claims 1, 4, 9, 44, 45, 51, 58, and 62 under 35 U.S.C. 102(a)(2) is withdrawn in view of Applicant’s amendment to the claims.
10. The rejection of claims 18 and 20 under 35 U.S.C. 103 is rendered moot by Applicant’s cancellation of these claims.
11. The rejection of claim 11 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claims.
12. The rejection of claim 124 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claims.
13. The rejection of claims 6, 7, and 15 under 35 U.S.C. 103 is rendered moot by Applicant’s cancellation of these claims.
14. The rejection of claims 1, 4, 9, 44, 58, and 62 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claims.
Objections/ Rejections Necessitated by Amendment
Claim Objections
15. Claim 129 is objected to because of the following informalities: in line 1, “the cell is a cell that is in a microbiota or a combination of cells that comprise a microbiota” should read “the population of cells are cells that are in a microbiota or that comprise a microbiota”. Appropriate correction is required.
Claim Interpretation
16. For the purpose of applying prior art, “is based on” of claim 126 and “is further based on” in claim 127 will be interpreted as “comprises” and “further comprises”, respectively.
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.
17. Claim(s) 1, 4, 9, 44, 45, 51, 58, 62, 124 and 126 – 129 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen (Chen, D., et al. Eye 31.6 (2017): 962-971.), hereinafter Chen which is cited on the IDS filed 06/02/2022 as evidenced by Sigma (Sigma (12/2022); HyStem-C Cell Culture Kit Product Information Sheet; 12/2022; https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/207/763/hysc010pis-ms.pdf?srsltid=AfmBOoofphZsDDN71LI5ygkfUvX-Ugjd-imoQJMyzqBGQalH9WcKHJws), hereinafter Sigma and Leger (Leger, Anthony J. St, et al. Immunity 47.1 (2017): 148-158.), hereinafter Leger in view of Paukkonen (US11324701B2; Filed 08/25/2017, Published 05/10/2022; previously cited), hereinafter Paukkonen in view of Wikstrom (Wikström, Jonna, et al. European journal of pharmaceutical sciences 47.2 (2012): 520-526; previously cited), hereinafter Wikstrom.
Regarding claim 1, Chen teaches a HyStem-C hydrogel comprising human corneal epithelial stem cells (“a population of cells” and “a lyophilization agent, wherein the lyophilization agent comprises a matrix, wherein the matrix comprises a hyaluronan gel wherein the population of cells is suspended in the hyaluron gel, and wherein the composition is free of cryoprotectant”) and culture media (“aqueous component”) (page 963, right col. last paragraph). Chen does not teach freezing the composition or removing at least 90% of the aqueous component of claim 1.
Regarding claim 4, Chen teaches HyStem-C is fully chemically-defined and based on three biocompatible components (page 968, left col. para. 1).
Regarding claim 51, Chen teaches human corneal epithelial stem cells (“stem cell”) (Abstract).
Regarding claim 58, Chen teaches cell culture medium (page 963, right col. last para.).
Regarding claim 124 and 126, Chen teaches HyStem-C comprises thiol modified hyaluronan (page 968, left col. para. 1).
Regarding claim 127, Chen teaches HyStem-C comprises a thiol-reactive crosslinker (page 968, left col. para. 1).
Regarding claim 128, Chen teaches HyStem-C comprises a thiol-modified denatured collagen (“collagen gel”) (page 968, left col. para. 1).
Regarding claim 129, Chen teaches the homeostasis and regeneration of corneal epithelia is maintained by the corneal epithelial stem cells (page 962, right col. para. 1). The ocular surface comprises a microbiome as evidenced by Leger (Summary; page 148, right col. last paragraph; page 149, left col. para. 1; page 152, right col. para. 2 – 3; page 156, right col. para. 3). Therefore, corneal epithelial stem cells are in a microbiota.
Chen does not teach “freezing” the composition or “removing at least 90% of the aqueous component” of claim 1 or “lyophilization is performed” of claim 9 or “free of DMSO” of claim 44 or the composition comprises polyethylene glycol of claim 45 or “lowering pressure” of claim 62. However, Chen teaches ocular surface diseases are sight threatening and often cause blindness (page 962, right col. para. 1). Chen teaches although corneal transplantation has achieved clinical success to treat limbal stem cell deficiency, there is an increasing shortage of corneal donors (page 962, right col. para. 1). Chen teaches corneal tissue engineering holds great promise for corneal transplantation to treat blinding corneal disease (page 962, right col. para. 1). Chen teaches HyStem-C hydrogel is a commercially available substrate which provides a 3D bio-scaffold and can support several kinds of stem cell expansion (page 963, left col. para. 2). Chen teaches HyStem-C hydrogel could promote the growth and stratification of limbal epithelial cells (page 968, right col. para. 1). Chen teaches preparation of the HyStem-C hydrogel (page 963, right col. para. 2) where the components are provided as lyophilized powders as evidenced by Sigma (page 2, left col. para. 1).
Regarding “freezing” and “removing at least 90% of the aqueous component” of claim 1 and “lowering pressure” of claim 62, Paukkonen teaches a method for freeze-drying a suspension of cells in a hydrogel comprising combining cells in a cell culture medium and a hydrogel to form a cell system and freeze drying where freeze drying comprises first freezing the cell system (“freezing” of claim 1) followed by lowering the pressure (“lowering pressure” of claim 62) of the frozen cell system where freeze drying is continued until the hydrogel moisture content is below 10% or even below 5% to produce a freeze-dried aerogel comprising a hydrogel, cells wherein the moisture content is 10% or less (“removing at least 90% of the aqueous component” of claim 1) (col. 2, lines 19 – 27 and lines 42 – 47; col. 6, lines 56 – 59; col. 18, lines 50 – 55; col. 19., lines 1 – 16; col. 20, lines 21 – 67; col. 21, lines 1 – 7). Paukkonen teaches freeze drying may also be called lyophilization (col. 20, line 25).
Regarding claim 9, Paukkonen teaches the cell system was pipetted into 15 ml tubes for freeze drying (col. 28, lines 15 – 67). Paukkonen does not teach the tubes were coated with collagen or have a membrane for cell attachment or growth (“without collagen coating” and “without membrane”).
Regarding claim 44, Paukkonen teaches DMSO is not desired in the present method of freeze drying cells in a hydrogel (col. 17, lines 42 – 43).
Regarding claim 45, Paukkonen teaches an embodiment where polyethylene glycol is added to the cell system (col. 17, lines 45 – 59).
Paukkonen teaches stem cells, progenitor cells, precursor cells, neuronal cells and hematopoietic cells and prokaryotic cells among others can be used with the freeze drying method (col. 2, lines 61 – 62; col. 7, line 33 – 48). Paukkonen teaches freeze-drying of complex or large mammalian cells causes irreversible damage to the cell and the freeze-dried cells tend to lose their 3D shape when dried and thus there is a need to find a method which may be used for freeze drying such cells to protect the cells during freezing (col. 1, lines 29 – 37). Paukkonen teaches for freeze-dried products, the product should be dry, active, shelf stable, clean and sterile, ethically acceptable, pharmaceutically elegant, readily soluble and simple to reconstitute and the process should be economically practicable (col. 33, lines 16 – 20). Paukkonen teaches the freeze-drying method produces a product that retained its activity after reconstitution, was sterile, elegant and readily soluble (col. 33, lines 21 – 23). Paukkonen teaches the freeze-dried product could be transferred in a car trunk and still showed viability (col. 33, lines 33 – 37).
Regarding claim 11, Wikstrom teaches freeze-drying a pellet of human retinal pigment epithelial cells at 6 x 105 cells/100 µL (page 521, right col.). Wikstrom teaches encapsulated human retinal pigment epithelial cells have been successfully used in experimental cell therapy of retinal degenerations and Parkinson’s disease but the long-term storage of encapsulated cells is still an unresolved question (Abstract). Wikstrom teaches reconstitution of viable encapsulated cells from dry form would benefit the development of cell therapy products (Abstract). Wikstrom teaches freeze-drying encapsulated cells and the cells showed partial viability after freeze-drying where cationic starch supported cell viability during freeze-drying (Abstract).
It would have been obvious prior to the effective filing date of the invention as claimed for the person or ordinary skill in the art to combine the teachings of Chen regarding a composition comprising human corneal epithelial stem cells on HyStem-C hydrogel in culture media with the teachings of Paukkonen regarding a method for freeze-drying a suspension of cells in a hydrogel with the teachings of Wikstrom regarding freeze-drying human ocular cells to arrive at the claimed method where a composition comprising a population of ocular cells, culture media, and HyStem-C are lyophilized by removing at least 90% of the culture media. One would have been motivated to combine the teachings of Chen, Pauukonen, and Wikstrom in a method to lyophilize ocular cells for therapy as Chen teaches corneal tissue engineering holds great promise for corneal transplantation to treat blinding corneal disease and Wikstrom teaches reconstitution of viable encapsulated cells from dry form would benefit the development of cell therapy products. One would have a reasonable expectation of success in combining the teachings as Chen teaches HyStem-C hydrogel is a lyophilized commercially available substrate which can support several kinds of stem cell and Paukkonen teaches the freeze-drying method produces a product that retained its activity after reconstitution, and Wikstrom teaches freeze-drying encapsulated cells and the cells showed partial viability after freeze-drying.
Applicant’s Arguments/ Response to Arguments
18. Applicant Argues: On page 7, para. 5 – 6 and page 8, para. 1 – 3, Applicant asserts Paukkonen does not anticipate amended claim 1.
Response to Argument: The anticipation rejection has been withdrawn and a new obviousness rejection of amended claim 1 is set forth above combining the teachings of Chen cited on the IDS filed 06/02/2022 and Paukkonen.
Applicant Argues: On page 8, last para. And page 9, para. 2 – 3, Applicant asserts that the teachings of Buchanan are for a different purpose.
Response to Argument: The rejection using the teachings of Buchanan have been withdrawn as Applicant has cancelled claims 18, 20, and 123.
Applicant Argues: On page 9, last para. - page 10, para. 1 – 3, Applicant asserts that neither Buchannan nor Paukkonen teach or suggest a hyaluronan gel matrix.
Response to Argument: In the new rejection of amended claim 1, Chen teaches HyStem-C.
Applicant Argues: On page 10, para. 5 – 6 – page 12, para. 1, Applicant asserts it would not have been obvious for one of ordinary skill in the art to arrive at the method by combining the teachings of Chen, Zhang, and Paukkonen.
Response to Argument: The previous claim rejection has been withdrawn in view of the amendment to claim 1. In the new rejection set forth, Chen cited on the IDS filed 06/02/2022 teaches HyStem-C that is a thiol modified hyaluronan comprising a thiol reactive cross-linker and a thiol-modified denatured collagen (page 968, left col. para. 1). Chen as evidenced by Sigma also teaches that HyStem-C is commercially available and is sold as lyophilized powders (page 963, right col. para. 2).
Applicant Argues: On page 12, para. 2 – 6 and page 13, para. 1 – 3, Applicant asserts that Wikstrom does not teach hyaluronan gel matrix of amended claim 1.
Response to Argument: This rejection has been withdrawn in view of amended claim 1. Wikstrom provides motivation for freeze-drying ocular cells and a reasonable expectation of success as Wikstrom teaches reconstitution of viable encapsulated cells from dry form would benefit the development of cell therapy products and freeze-drying encapsulated cells and the cells showed partial viability after freeze-drying where cationic starch supported cell viability during freeze-drying (Abstract).
Conclusion
No claims 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.
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/Z.M.B./Examiner, Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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